Substituted imidazo [1, 5-a] pyridine n-heterocyclic carbene (NHC) ligands, catalyst complexes thereof, and methods of their use

Abstract

The present disclosure provides substituted imidazo [1, 5-a] pyridine N-heterocyclic carbene (NHC) ligands, catalyst complexes thereof, and methods of their use. The present disclosure further provides synthetic methods of making N-heterocyclic carbene ligands, as well as catalyst complexes thereof.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority under 35 USC §119(e) to U.S. Provisional Patent Application No. 63 / 318,481, filed on March 10, 2022, which is incorporated herein by reference in its entirety.

[0003] Statement Regarding Federally Funded Research

[0004] This invention was made with government support under Grant No. CHE-1650766 awarded by the National Science Foundation and Grant No. R35GM133326 awarded by the National Institutes of Health. The government has certain rights in this invention. Background Art

[0005] Buchwald dialkylbiarylphosphines are the most widely used class of ligands in catalysis. A key application of these electron-rich and bulky phosphines is to promote a wide range of C-C and C-X bond forming processes in classical Pd(O) / (II) cross-coupling chemistry. The products of these processes are of vital importance in both industrial and academic settings, particularly in the fields of medicinal chemistry, drug discovery, biochemistry, agricultural chemistry, natural product synthesis, small molecule synthesis, and polymer synthesis. The applications of Buchwald dialkylbiarylphosphines are not limited to Pd(O) / (II) catalysis, and these ligands are also among the most popular supported catalysts in the optimization and development of new processes using Pd, Au, Cu, Ni, Rh, and Ir complexes in addition to cross-coupling. There are currently many commercially available dialkylbiarylphosphine-type ligands with a general dialkyl-biarylphosphine architecture.

[0006] The highly desirable properties of dialkylbiarylphosphines result from the combination of an electron-rich dialkylphosphine moiety with an ortho-substituted biaryl motif that can be modified to accommodate sterically bulky, electron-rich, coordinating, or sterically differentiated substituents at the ortho, meta, or para positions of the biaryl ring. Such modifications have two primary effects: (1) electronically, the electron-rich dialkylphosphine promotes oxidative addition; and (2) sterically, the pivotal biaryl arrangement of the dialkylbiarylphosphine (i.e., the vertical arrangement of the biaryl ring) stabilizes the reaction intermediates through sterically confined interactions between the phosphine-metal complex and the ortho-aromatic ring in a rigid five-membered arrangement. This unique feature makes Buchwald dialkylbiarylphosphines highly valuable in Pd, Au, Cu, Ni, Rh, and Ir catalysis, where two effects are generally observed: (1) enhanced reactivity compared to other ligands; and (2) unique reactivities that cannot be achieved with other ligands.

[0007] Despite the tremendous success of Buchwald dialkylbiarylphosphines, the development of novel N-heterocyclic carbene (NHC) analogs remains elusive due to the lack of suitable NHC scaffolds.

[0008] Therefore, there is a need in the art for NHC ligands and / or catalyst complexes thereof, and methods of using the same. The present disclosure addresses this need. Summary of the Invention

[0009] In one aspect, the present disclosure provides compounds of formula (I), wherein T 1 、T 2 、T 3 、R 2 、R 3 、R 4 and X is as defined elsewhere herein:

[0010]

[0011] In another aspect, the present disclosure provides compounds of formula (II), wherein T 1 、T 2 、T 3 、R 2 、R 3 、R 4 , M, L, X, m and n are as defined elsewhere herein:

[0012]

[0013] In another aspect, the present disclosure provides a method of promoting a reaction between a pair of compounds selected from:

[0014] (a) Boric acid and nitroarene;

[0015] (b) alkyl sulfoxides and aniline;

[0016] (c) thiophenol and aniline;

[0017] (d) aryl halides and hydrazines;

[0018] (e) an aryl methanesulfonate or aryl toluenesulfonate and boronic acid;

[0019] (f) an aryl methanesulfonate or aryl toluenesulfonate and an aniline;

[0020] (g) arylsulfamate and boronic acid;

[0021] (h) Arylsulfamates and anilines;

[0022] (i) aryl halide and hydroxide salts;

[0023] (j) aryl methyl sulfide and aniline;

[0024] (k) aryl sulfoxides and anilines;

[0025] (1) amines and aryl chlorides;

[0026] (m) aryl chloride and boronic acid;

[0027] (n) aryl fluorides and anilines; and

[0028] (o) Alkynes and nitroarenes;

[0029] The method comprises contacting the compound pair with a compound of the disclosure according to conditions described elsewhere herein.

[0030] In another aspect, the present disclosure provides a method for preparing a compound of formula (IV), wherein T 1 、T 2 、T 3 、R 2 、R 3a 、R 3b 、R 3c 、R 3d 、R 3e 、R 4a 、R 4b 、R 4c 、R 4d 、R 4e and X is as defined elsewhere herein:

[0031]

[0032] The method comprises causing (Z):

[0033]

[0034] With (Y):

[0035]

[0036] Contact in the presence of paraformaldehyde and acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The drawings illustrate generally, by way of example and not by way of limitation, various embodiments of the application.

[0038] Figure 1 A comparison of the general representations of N-heterocyclic carbenes (NHCs) and Buchwald dialkylbiarylphosphines of the present disclosure is provided.

[0039] Figure 2A-2B Provided are throw-away ligands having an allyl group ( Figure 2A ) and pyridine-type disposable ligands ( Figure 2B ) structure of the imidazo[1,5-α]pyridine NHC-Pd(II) complex.

[0040] Figure 3A-3C Provided are structures of NHC ligands of the present disclosure, wherein the 5-position of the imidazo[1,5-α]pyridine is substituted with a higher order 2,4,6-trialkyl-substituted aryl or a peralkyl-substituted aryl ( Figure 3A ), 2,4,6-tricycloalkyl substituted aryl ( Figure 3B ) or 2,6-dialkyl-substituted aryl ( Figure 3C ).

[0041] Figure 4A-4B Provided are structures of NHC ligands of the present disclosure, wherein the 5-position of the imidazo[1,5-α]pyridine is substituted with a dialkyloxy group having at least 2,6- Figure 4A ) or 2-aminoalkyl substituted ( Figure 4B ) is substituted with an aryl substituent.

[0042] Figure 5 Provided are structures of ligands of the present disclosure, which combine the design principles of L-type ligands of imidazo[1,5-a]pyridines with the bulky yet flexible properties of N-wingtip substitutions.

[0043] Figures 6A-6C Provided are structures of ligands of the present disclosure wherein the 5-position of the imidazo[1,5-α]pyridine is substituted with a cycloalkyl substituent ( Figure 6A ), 3,5-dialkyl-substituted aryl ( Figure 6B ) or ortho-substituted aryl ( Figure 6C ).

[0044] Figure 7A-7B Provides 52 x-ray structures, frontal views ( Figure 7A ) and side view ( Figure 7B ).

[0045] Figure 8A-8B Provides 39 x-ray structures, frontal view ( Figure 8A ) and side view ( Figure 8B ).

[0046] Figure 9A-9B Provides an x-ray structure of 56, frontal view ( Figure 9A ) and side view ( Figure 9B ).

[0047] Figures 10A-10FThe following topographical space maps determined at the B3LYP 6-311++g(d,p) level are provided: [Cu(33)Cl]( Figure 10A )、[Cu(34)Cl]( Figure 10B )、[Cu(17)Cl]( Figure 10C )、[Cu(35)Cl]( Figure 10D )、[Cu(36)Cl]( Figure 10E ) and [Cu(19)Cl]( Figure 10F ).

[0048] Figures 11A-11C Representations of the HOMO (π-donating orbital), HOMO-1 (σ-donating orbital), and LUMO (π-accepting orbital) calculated at the B3LYP 6-311++g(d,p) level are provided, respectively.

[0049] Figure 12A : Substrate scope for the Suzuki-Miyaura cross-coupling of nitroarenes using a well-defined, air- and moisture-stable NHC precatalyst; a Conditions: nitroarene (1.0 eq), boronic acid (1.5 eq), 39 (5 ​​mol%), K3PO4 (3 eq), 1,4-dioxane (0.5 M), TD (10 mol%), H2O (3 eq), 36 h, isolated yield; b 16 hours; c 2 equivalents of boric acid; d 10 mol% 39; TDA = (tris(3,6-dioxaheptyl)amine). Figure 12B : A plot of conversion versus time in the cross-coupling of 4-nitroanisole and phenylboronic acid catalyzed by the NHC catalysts of the present disclosure.

[0050] Figure 13A : Substrate scope for the Suzuki-Miyaura cross-coupling of nitroarenes using a well-defined, air- and moisture-stable [Pd-PEPPSI]NHC precatalyst; a Nitroarene (1.0 eq), boronic acid (1.5 eq), 47 (5 mol%), K3PO4 (3 eq), 1,4-dioxane (0.5 M), TDA (10 mol%); H2O (3 eq), 36 h, isolated yield; b 2 equivalents of boronic acid; TDA = (tris(3,6-dioxaheptyl)amine). Figure 13B : A plot of conversion versus time in the cross-coupling of 4-nitroanisole with phenylboronic acid catalyzed by the NHC catalysts of the present disclosure.

[0051] Figure 14A: Substrate scope of anilines in the Buchwald-Hartwig amination of alkyl sulfoxides (Ar-S(=O)(alkyl)). Figure 14B : Substrate scope of sulfoxides (ie, varying aryl components) in the Buchwald-Hartwig amination of alkyl sulfoxides. Figure 14C : Substrate scope of sulfoxides (ie, varying alkyl components) in the Buchwald-Hartwig amination of alkyl sulfoxides. Figure 14D : Example of late-stage functionalization using NHC-Pd-catalyzed Buchwald-Hartwig amination of alkyl sulfoxides. Figure 14E : Optimized conditions for the Buchwald-Hartwig amination of alkyl sulfoxides are provided.

[0052] Figure 15A : Substrate scope of anilines in the Buchwald–Hartwig amination of thiophenols. Figure 15B : Substrate scope of thiophenols in the Buchwald-Hartwig amination of thiophenols. Figure 15C : Optimized conditions for the Buchwald-Hartwig amination of thiophenols are provided.

[0053] Figure 16A : substrate scope of aryl chlorides in reaction sequences involving hydrazino and aromatization; a Does not contain THF. Figure 16B : substrate scope of aryl bromides in reaction sequences involving hydrazino and aromatization; a TFA-free. Figure 16C : Example of late-stage functionalization using NHC-Pd-catalyzed hydrazine formation and subsequent aromatization. Figure 16D : Optimized conditions for the hydrazine / aromatization sequence are provided.

[0054] Figure 17A : Substrate scope of Suzuki-Miyaura cross-coupling with aryl methanesulfonates; conditions: aryl methanesulfonate (1.0 equiv), arylboronic acid (4.5 equiv), K3PO4 (3.0 equiv), 43 (5 mol%), iPrOH (0.2 M), 130°C, 12 h. Figures 17B-17C : Optimized conditions for Suzuki-Miyaura cross-coupling with aryl methanesulfonates are provided; L1(9), L2(35) and L3(34).

[0055] Figure 18A : Substrate scope for Buchwald-Hartwig cross-coupling with aryl methanesulfonates; conditions: aryl methanesulfonate (1.0 equiv), aniline (1.2 equiv), K3PO4 (2.0 equiv), 42 (5 mol%), tAmOH (0.2 M), 120°C, 12 h. Figure 18B: Optimized conditions for Buchwald-Hartwig cross-coupling with aryl methanesulfonates are provided; L1 (9), L2 (35) and L3 (34).

[0056] Figure 19A : Substrate scope of Suzuki-Miyaura cross-coupling with arylsulfamate; conditions: arylsulfamate (1.0 equiv), arylboronic acid (4.5 equiv), K3PO4 (3.0 equiv), 42 (5 mol%), iPrOH (0.2 M), 130°C, 12 h. Figure 19B : Optimized conditions for Suzuki-Miyaura cross-coupling with arylsulfamates are provided; L1(9), L2(35) and L3(34).

[0057] Figure 20A : Substrate scope of Buchwald-Hartwig cross-coupling with arylsulfamate; conditions: arylsulfamate (1.0 equiv), aniline (1.2 equiv), K3PO4 (2.0 equiv), 42 (5 mol%), tAmOH (0.2 M), 120°C, 12h. Figure 20B : Optimized conditions for Buchwald-Hartwig cross-coupling with arylsulfamates are provided; L1 (9), L2 (35) and L3 (34).

[0058] Figures 21A-21E Non-limiting examples of additional reactions catalyzed using the NHC ligands and / or catalyst complexes described herein are provided, including the hydroxylation of aryl chlorides ( Figure 21A ), Buchwald-Hartwig amination of alkyl sulfides ( Figure 21B ), Buchwald-Hartwig amination of aryl sulfoxides ( Figure 21C ), Buchwald-Hartwig amination of aryl chlorides ( Figure 21D ) and aryl chlorides by Suzuki-Miyaura cross-coupling ( Figure 21E ). DETAILED DESCRIPTION

[0059] Reference will now be made in detail to certain embodiments of the disclosed subject matter, examples of which are partially illustrated in the accompanying drawings.While the disclosed subject matter will be described in conjunction with the enumerated claims, it will be understood that the illustrated subject matter is not intended to limit the claims to the disclosed subject matter.

[0060] Throughout this document, values ​​expressed in range format should be interpreted in a flexible manner to include not only the values ​​explicitly listed with the range limits, but also all individual values ​​or subranges encompassed within the range, as if each value and subrange were explicitly listed. For example, a range of "about 0.1% to about 5%" or "about 0.1% to 5%" should be interpreted to include not only about 0.1% to about 5%, but also individual values ​​(e.g., 1%, 2%, 3%, and 4%) and subranges (e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. Unless otherwise indicated, the statement "about X to Y" has the same meaning as "about X to about Y." Similarly, unless otherwise indicated, the statement "about X, Y, or about Z" has the same meaning as "about X, about Y, or about Z."

[0061] In this document, unless the context clearly dictates otherwise, the terms "a," "an," or "the" are used to include one or more than one. Unless otherwise indicated, the term "or" is used to refer to a non-exclusive "or." The description "at least one of A and B" or "at least one of A or B" has the same meaning as "A, B, or A and B." In addition, it should be understood that the expressions or terms used herein are used for descriptive purposes only and not for limiting purposes unless otherwise defined. Any section headings are used to aid reading of the document and are not to be construed as limitations; information related to the section heading may appear within or outside that particular section. All publications, patents, and patent documents mentioned in this document are incorporated herein by reference in their entirety, as if individually incorporated by reference.

[0062] In the methods described herein, the actions may be performed in any order unless a temporal or operational order is explicitly specified. Furthermore, specified actions may be performed in parallel unless explicit claim language specifies that they be performed separately. For example, a claimed act of performing X and a claimed act of performing Y may be performed simultaneously in a single operation, and the resulting method would fall within the literal scope of the claimed method.

[0063] introduce

[0064] Despite the tremendous success of Buchwald dialkylbiarylphosphines, the development of related N-heterocyclic carbene (NHC) ligands has been difficult because the common NHC architecture cannot support the biaryl arrangement of dialkylbiarylphosphines to stabilize the reactive ligand-metal intermediate through spatially confined rigid five-membered interactions.

[0065] NHC ligands themselves are recognized as very valuable ligands due to (1) stronger σ-donation and π-acceptance (see phosphine ligands), (2) the unique umbrella shape of the steric body around the donor center (see the cone of phosphine), and (3) the ease of modification of the peripheral N-wing tips and scaffold to further tune the steric and electronic properties of the ligand. Therefore, NHC is one of the most popular ligands in transition metal catalysis, organocatalysis, organic synthesis and materials science, and many NHCs are currently commercially available.

[0066] The present disclosure provides a spatially confined L-type NHC technology platform for developing novel cross-coupling reactions that have not been achieved using other NHC ligands, as well as improving the efficiency of existing cross-coupling methods using other ligands ( Figure 1 ). In addition, this disclosure describes: (1) novel spatially defined L-biaryl NHC ligands on an imidazo[1,5-a]pyridine framework; (2) well-defined, air- and moisture-stable NHC complexes with transition metals; and (3) the use of NHC-catalyst complexes in palladium-catalyzed cross-coupling reactions. Additionally, feasibility studies have demonstrated the synthesis of well-defined complexes with Au, Cu, Ag, and Rh.

[0067] As described herein, in certain embodiments, an aryl substituent is placed at the C5 position of the imidazo[1,5-a]pyridine scaffold, which, without wishing to be bound by theory, results in a well-defined, rigid vertical arrangement of the biaryl moiety, which enables a stabilizing interaction between the idiomeric C5-aromatic ring and the metal center coordinated to the NHC carbon, thereby providing the geometry characteristic of a Buchwald dialkylbiarylphosphine with an NHC linkage.

[0068] In one aspect, the present disclosure describes the following classes, features, and / or aspects of compounds disclosed herein: (1) well-defined complexes; (2) C5 differentiation; (3) RuPhos NHC analogs; (4) N2 differentiation; and (5) C5 alkyl substitution, C5 meta-aryl substitution, and C5-mono-ortho-aryl substitution.

[0069] Well-defined complexes. Development of well-defined, spatially confined Pd(II)-NHC complexes of imidazo[1,5-a]pyridines ( Figure 2A-2BIn particular, it has been demonstrated herein that the use of Pd(II)-NHC-cinnamyl complexes with L-imidazo[1,5-a]pyridine ligands of the general formula [Pd(NHC)(cin)Cl] yields significantly more active catalysts for the Suzuki cross-coupling of nitroarenes (R-NO2) based on the imidazo[1,5-a]pyridine scaffold. In certain embodiments, well-defined PEPPSI-type catalysts with L-imidazo[1,5-a]pyridine ligands of the general formula [Pd(NHC)(3-Cl-py)Cl2] are preferred due to ease of synthesis and stability.

[0070] C5 differentiation. Development of new catalysts with spatial differentiation at the C5 aromatic ring ( Figure 3A-3C ). Ortho-substituted biaryl motifs are crucial for activity due to the stabilizing interaction between the C5-aromatic ring and the metal center coordinated to the NHC carbon. Therefore, rational modification of C5 substitution has a significant impact on the fundamental steps of the catalytic cycle. In particular, we have demonstrated the synthesis and catalytic activity of L-imidazo[1,5-a]pyridine ligands in which the C5 aromatic ring is substituted with any number of substituents, including but not limited to: (a) higher-order 2,4,6-trialkyl and peralkyl hydrocarbon chains; (b) 2,4,6-trialkyl cyclic hydrocarbon chains; and (c) sterically flexible 2,6-dialkyl hydrocarbon chains, which, in certain embodiments, provide steric stabilization at the 4-position of the aromatic ring.

[0071] RuPhos NHC analogs. Development of highly active, spatially confined L-type NHC ligands analogous to RuPhos (i.e., 2,6-alkoxyaryl groups at the 5-position of imidazo[1,5-a]pyridines) ( Figure 4A-4B ). In particular, this article provides a structure-activity relationship study of spatially confined L-type NHC ligands containing imidazo[1,5-a]pyridine, thereby establishing a spatial reactivity map and demonstrating the steric influence of the C5 aromatic ring and the N2 aromatic ring. In one aspect, these findings have led to the development of highly active carbene analogs of RuPhos, characterized by the presence of electron-rich chelating 2,6-Oi-Pr2-substitution on the C5 aromatic ring. Related ligands with chelating heteroatoms and steric changes in the ortho position of the C5 aromatic ring have also been developed (e.g., 2-NR2-phenyl, 2,6-dimethoxyphenyl, and 2,4,6-trimethoxyphenyl).

[0072] N2 differentiation. Development of novel catalysts with spatial differentiation at the N2 position ( Figure 5The unique umbrella-shaped shape of NHC ligands enables the use of peripheral N-wingtip modifications to tune the steric and electronic properties of the ligand. A new class of spatially confined L-type NHC ligands has been developed, featuring bulky N2-substituted imidazo[1,5-a]pyridines. In particular, the synthesis and catalytic activity of N2-substituted catalysts with the general formula Ar=2,6-(Ph2CH2)2-4-R-C6H2 (R=Me, OMe, F) are demonstrated. This class of catalysts combines the bulky yet flexible characteristics of the IPr* series of NHC ligands with L-type imidazo[1,5-a]pyridines.

[0073] Development of new catalysts containing C5-alkyl, C5-meta-aryl and C5-mono-ortho-aryl substitutions ( Figures 6A-6C Feasibility studies have demonstrated the synthesis of spatially constrained NHC ligands with imidazo[1,5-a]pyridines characterized by C5-alkyl substitution, C5-meta-aryl substitution, or C5-mono-ortho-aryl substitution instead of the more common aromatic ring. This disclosure demonstrates the use of the catalysts described herein in palladium catalysis, however, these classes of ligands are expected to exhibit unique reactivity with metals that do not require di-ortho substitution for the reductive elimination step, including but not limited to Ru, Rh, Ir, Cu, Ag, and Ni.

[0074] definition

[0075] As used herein, the term "about" can allow a degree of variation in a value or range, for example, within 10%, within 5%, or within 1% of the stated value or stated limit of the range, and includes the exact stated value or range.

[0076] As used herein, the term "acyl" refers to a group containing a carbonyl moiety, wherein the group is bonded via the carbonyl carbon atom. The carbonyl carbon atom is bonded to hydrogen to form a "formyl" group or to another carbon atom, which can be part of an alkyl, aryl, aralkylcycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, etc. The acyl group can include 0 to about 12, 0 to about 20, or 0 to about 40 additional carbon atoms bonded to the carbonyl group. The acyl group can include double or triple bonds within the meaning herein. Acryloyl is an example of an acyl group. Acyl groups can also include heteroatoms within the meaning herein. Nicotinoyl (pyridyl-3-carbonyl) is an example of an acyl group within the meaning herein. Other examples include acetyl, benzoyl, phenylacetyl, pyridylacetyl, cinnamoyl, and acryloyl, etc. When the group containing the carbon atom bonded to the carbonyl carbon atom contains a halogen, the group is referred to as a "haloacyl" group. An example is trifluoroacetyl.

[0077] As used herein, the term "alkenyl" refers to straight and branched chain and cyclic alkyl groups as defined herein, except that there is at least one double bond between two carbon atoms. Thus, an alkenyl group has 2 to 40 carbon atoms, or 2 to about 20 carbon atoms, or 2 to 12 carbon atoms, or in some embodiments, 2 to 8 carbon atoms. Examples particularly include, but are not limited to, vinyl, -CH=C=CCH2, -CH=CH(CH3), -CH=C(CH3)2, -C(CH3)=CH2, -C(CH3)=CH(CH3), -C(CH2CH3)=CH2, cyclohexenyl, cyclopentenyl, cyclohexadienyl, butadienyl, pentadienyl, and hexadienyl.

[0078] As used herein, term " alkoxy " refers to that oxygen atom is connected to alkyl (comprising cycloalkyl) as defined herein.The example of linear alkoxy includes but is not limited to methoxyl group, ethoxyl group, propoxyl group, butoxyl group, amyloxy group, hexyloxy group etc.The example of branched alkoxy includes but is not limited to isopropyloxy, sec-butoxy, tert-butoxy, isopentyloxy, isohexyloxy group etc.The example of cyclic alkoxy includes but is not limited to cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy group etc.Alkoxy group can comprise approximately 1 to approximately 12, approximately 1 to approximately 20 or approximately 1 to approximately 40 carbon atoms that are bonded to oxygen atom, and can further comprise double bond or triple bond, and can also comprise heteroatom.For example, allyloxy or methoxyethoxy are also the alkoxy in this paper's implication, and methylenedioxy is also alkoxy in the case that two adjacent atoms of structure are replaced by it.

[0079] As used herein, the term "alkynyl" refers to straight and branched chain alkyl groups, except that there is at least one triple bond between two carbon atoms. Thus, alkynyl groups have from 2 to 40 carbon atoms, from 2 to about 20 carbon atoms, or from 2 to 12 carbons, or in some embodiments from 2 to 8 carbon atoms. Examples include, but are not limited to, -C≡CH, -C≡C(CH3), -C≡C(CH2CH3), -CH2C≡CH, -CH2C≡C(CH3), and -CH2C≡C(CH2CH3).

[0080] As used herein, the term "alkyl" refers to a straight chain and branched chain alkyl and cycloalkyl group having from 1 to 40 carbon atoms, from 1 to about 20 carbon atoms, from 1 to 12 carbon atoms, or in some embodiments from 1 to 8 carbon atoms. The example of a straight chain alkyl group includes those having from 1 to 8 carbon atoms, such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl. The example of a branched chain alkyl group includes but is not limited to isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, isopentyl and 2,2-dimethylpropyl. As used herein, the term "alkyl" encompasses normal alkyl, isoalkyl and anteisoalkyl (anteisoalkyl) and other branched forms of alkyl groups. Representative substituted alkyl groups can be substituted once or multiple times by any of the groups listed herein (e.g., amino, hydroxyl, cyano, carboxyl, nitro, sulfenyl, alkoxy and halogen groups).

[0081] As used herein, the term "amine" refers to primary, secondary, and tertiary amines having, for example, the formula N(group) 3, wherein each group can independently be H or non-H, such as alkyl, aryl, etc. Amines include, but are not limited to, R-NH2, such as alkylamines, arylamines, alkylarylamines; R2NH, wherein each R is independently selected, such as dialkylamines, diarylamines, arylalkylamines, heterocyclylamines, etc.; and R3N, wherein each R is independently selected, such as trialkylamines, dialkylarylamines, alkyldiarylamines, triarylamines, etc. The term "amine" also includes ammonium ions as used herein.

[0082] As used herein, the term "amino" refers to -NH2, -NHR, -NR2, -NR3 + Substituents of the form wherein each R is independently selected, and the protonated form of each, except -NR3 which cannot be protonated + Thus, any compound substituted with an amino group can be considered an amine. "Amino" within the meaning herein can be a primary, secondary, tertiary or quaternary amino group. "Alkylamino" groups include monoalkylamino, dialkylamino and trialkylamino groups.

[0083] As used herein, the term "aniline" refers to an amine having at least one aryl or heteroaryl substituent.

[0084] As used herein, the term "aralkyl" refers to an alkyl group as defined herein in which a hydrogen or carbon bond of the alkyl group is replaced by a bond to an aryl group as defined herein. Representative aralkyl groups include benzyl and phenylethyl groups, as well as fused (cycloalkylaryl)alkyl groups, such as 4-ethyl-indanyl. Aralkenyl groups are alkenyl groups as defined herein in which a hydrogen or carbon bond of the alkyl group is replaced by a bond to an aryl group as defined herein.

[0085] As used herein, the term "aroyl" refers to an aryl group as defined elsewhere herein, substituted at any position with a carbonyl moiety (i.e., C(=O)). The term "aroyl" used in combination with another term (e.g., chloride) indicates that the carbonyl group attached to the aryl group is substituted with a substituent defined by the terms used in the combination. For example, PhC(=O)Cl (i.e., benzoyl chloride) is an aryl chloride.

[0086] As used herein, the term "aryl" refers to a cyclic aromatic hydrocarbon group that does not contain heteroatoms in the ring. Thus, aryl includes, but is not limited to, phenyl, azulenyl, heptalenyl, biphenyl, indacenyl, fluorenyl, phenanthrenyl, triphenylene, pyrenyl, naphthacenyl, In some embodiments, the aryl group contains about 6 to about 14 carbon atoms in the ring portion of the group. As defined herein, the aryl group can be unsubstituted or substituted. Representative substituted aryl groups can be monosubstituted or substituted more than once, such as, but not limited to, phenyl substituted at any one or more of the 2, 3, 4, 5 or 6 positions of the phenyl ring or naphthyl substituted at any one or more of its 2 to 8 positions. The term "aryl" is used in combination with another term (e.g., especially iodide, chloride, boric acid and magnesium halide) to indicate that the aryl group is substituted at one or more positions by the substituent defined by the term used in the combination. For example, aryl chloride indicates that the aryl group is substituted by at least one chlorine.

[0087] As used herein, the term "atmospheric pressure" refers to the pressure in the atmosphere under standard conditions. Thus, 1 atmosphere is a pressure of 101 kPa, 2 atmospheres is a pressure of 202 kPa, and so on.

[0088] As used herein, the term "counter anion" refers to a negatively charged ion that accompanies a cationic species (i.e., a positively charged ion) to maintain electrical neutrality. For example, chloride ion (Cl - ) is the sodium in NaCl (Na + ) of the counter anion. Non-limiting examples of counter anions include F - 、Cl - Br - , I - 、H - 、N3 - 、PhCH ＝ CHCH2 - 、PhCH - CH=CH2、F3CS(=O)2O - (OTf), (F3CS(=O)2)2N - (NTf2), F3CC(=O)O - (TFA), BF4 - and PF6- .

[0089] As used herein, the term "cycloalkyl" refers to cyclic alkyl groups such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In some embodiments, the cycloalkyl group may have 3 to about 8-12 ring members, while in other embodiments, the number of ring carbon atoms ranges from 3 to 4, 5, 6, or 7. Cycloalkyl groups further include polycyclic cycloalkyl groups such as, but not limited to, norbornyl, adamantyl, bornyl, kenyl, isokenyl, and carenyl, as well as fused rings such as, but not limited to, decahydronaphthyl. Cycloalkyl groups also include rings substituted with straight or branched chain alkyl groups as defined herein. Representative substituted cycloalkyl groups may be monosubstituted or substituted more than once, such as, but not limited to, 2,2-, 2,3-, 2,4-, 2,5-, or 2,6-disubstituted cyclohexyl groups or mono-, di-, or tri-substituted norbornyl or cycloheptyl groups, which may be substituted with, for example, amino, hydroxyl, cyano, carboxyl, nitro, thio, alkoxy, and halogen groups. The term "cycloalkenyl," alone or in combination, refers to a cyclic alkenyl group.

[0090] As used herein, the term "electrophilic" refers to an electrophilic N 1. S N 2 and carbonyl [1,2]-addition) in which the electron pair is accepted to form a bond with the nucleophile. Non-limiting examples of electrophiles include alkyl halides (e.g., MeI), benzyl halides (e.g., BnBr), dihalides (e.g., Br2), aldehydes (e.g., Ph-CHO), acyl halides (e.g., Ph(C=O)Cl), N-electrophiles (e.g., RC(=O)ONR2), and O-electrophiles (e.g., RC(=O)O2R).

[0091] As used herein, the term "epoxy functional group" or "epoxy substituted" refers to a functional group in which an oxygen atom (i.e., an epoxy substituent) is directly attached to two adjacent carbon atoms of a carbon chain or ring system. Examples of epoxy substituted functional groups include, but are not limited to, 2,3-epoxypropyl, 3,4-epoxybutyl, 4,5-epoxypentyl, 2,3-epoxypropoxy, epoxypropoxypropyl, 2-glycidyloxyethyl, 3-glycidyloxypropyl, 4-glycidyloxybutyl, 2-(glycidyloxycarbonyl)propyl, 3-(3,4-epoxycyclohexyl)propyl, 2-(3,4-epoxycyclohexyl)ethyl, 2-(2,3-epoxycyclopentyl)ethyl, 2-(4-methyl-3,4-epoxycyclohexyl)propyl, 2-(3,4-epoxy-3-methylcyclohexyl)-2-methylethyl, and 5,6-epoxyhexyl.

[0092] As used herein, the terms "halo," "halogen," or "halide" group, by themselves or as part of another substituent, mean, unless otherwise stated, a fluorine, chlorine, bromine, or iodine atom.

[0093] As used herein, the term "haloalkyl" group includes monohaloalkyl, polyhaloalkyl (wherein all halogen atoms may be the same or different) and perhaloalkyl (wherein all hydrogen atoms are replaced by halogen atoms such as fluorine). Examples of haloalkyl include trifluoromethyl, 1,1-dichloroethyl, 1,2-dichloroethyl, 1,3-dibromo-3,3-difluoropropyl, perfluorobutyl, and the like.

[0094] As used herein, the term "heteroaralkynyl" refers to an alkynyl group as defined herein, wherein a hydrogen or carbon bond of the alkynyl group is replaced by a bond to a heteroaryl group as defined herein. Representative aralkynyl groups include, but are not limited to, 2-ethynylpyridine and 2-ethynylthiophene.

[0095] As used herein, the term "heteroaryl" refers to an aromatic ring compound containing 5 or more ring members, one or more of which is a heteroatom, such as, but not limited to, N, O, and S; for example, a heteroaryl ring can have 5 to about 8-12 ring members. Heteroaryls are various heterocyclic groups with aromatic electronic structures. A heteroaryl designated as a C2-heteroaryl can be a 5-ring ring with two carbon atoms and three heteroatoms, a 6-ring ring with two carbon atoms and four heteroatoms, and so on. Similarly, a C4-heteroaryl can be a 5-ring ring with one heteroatom, a 6-ring ring with two heteroatoms, and so on. The number of carbon atoms plus the number of heteroatoms equals the total number of ring atoms. Heteroaryl includes but is not limited to following groups: such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, thienyl, benzothienyl, benzofuranyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridyl, isoxazolopyridyl, thiazolinyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolyl, isoquinolyl, tetrahydroquinolyl, quinoxalinyl and quinazolinyl.Heteroaryl can be unsubstituted, or can be substituted by a group as discussed herein.Representative substituted heteroaryl can be substituted once or many times by a group as listed herein.

[0096] Additional examples of aryl and heteroaryl groups include, but are not limited to, phenyl, biphenyl, indenyl, naphthyl (1-naphthyl, 2-naphthyl), N-hydroxytetrazolyl, N-hydroxytriazolyl, N-hydroxyimidazolyl, anthracenyl (1-anthryl, 2-anthryl, 3-anthryl), thienyl (2-thienyl, 3-thienyl), furanyl (2-furyl, 3-furyl), indolyl, oxadiazolyl, isoxazolyl, quinazolinyl, fluorenyl, xanthenyl, isoindanyl, benzhydryl, acridinyl, thiazolyl, pyrrolyl (2-pyrrolyl), pyrazolyl (3-pyrazolyl), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), triazolyl (1,2,3-triazolyl), 1-yl, 1,2,3-triazol-2-yl, 1,2,3-triazol-4-yl, 1,2,4-triazol-3-yl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl), , 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), benzo[b]furanyl (2-benzo[b]furanyl, 3-benzo[b]furanyl, 4-benzo[b]furanyl, 5-benzo[b]furanyl, 6-benzo[b]furanyl, 7-benzo[b]furanyl), 2,3-dihydro-benzo[b]furanyl (2-(2,3-dihydro-benzo[b]furanyl), 3-(2,3-dihydro-benzo[b]furanyl), 4-(2,3-dihydro-benzo[b]furanyl), 5-(2,3-dihydro-benzo[b]furanyl), 6-(2,3-dihydro-benzo[b]furanyl), thiophenyl (2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5-benzo[b]thiophenyl, 6-benzo[b]thiophenyl, 7-benzo[b]thiophenyl), 2,3-dihydro-benzo[b]thiophenyl (2-(2,3-dihydro-benzo[b]thiophenyl), 3-(2,3-dihydro-benzo[b]thiophenyl), 4-(2,3-dihydro-benzo[b]thiophenyl), 5-(2,3-dihydro-benzo[b]thiophenyl), 6-(2,3-dihydro-benzo[b]thiophenyl), 7-(2,3-dihydro-benzo[b]thienyl)), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), indazole (1-indazolyl, 3-indazolyl, 4-indazolyl, 5-indazolyl, 6-indazolyl, 7-indazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzo[b]thienyl) imidazolyl, 6-benzimidazolyl, 7-benzimidazolyl, 8-benzimidazolyl), benzoxazolyl (1-benzoxazolyl, 2-benzoxazolyl), benzothiazolyl (1-benzothiazolyl, 2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), carbazolyl (1-carbazolyl, 2-carbazolyl, 3-carbazolyl, 4-carbazolyl), 5H -dibenzo[b,f]azepine (5H-dibenzo[b,f]azepine-1-yl, 5H-dibenzo[b,f]azepine-2-yl, 5H-dibenzo[b,f]azepine-3-yl, 5H-dibenzo[b,f]azepine-4-yl, 5H-dibenzo[b,f]azepine-5-yl), 10,11-dihydro-5H-dibenzo[b,f]azepine (10,1 1-dihydro-5H-dibenzo[b,f]azepin-1-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-2-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-3-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-4-yl, 10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl), etc.

[0097] As used herein, the term "heterocyclylalkyl" refers to an alkyl group as defined herein in which a hydrogen or carbon bond of the alkyl group as defined herein is replaced by a bond to a heterocyclyl group as defined herein. Representative heterocyclylalkyl groups include, but are not limited to, furan-2-ylmethyl, furan-3-ylmethyl, pyridin-3-ylmethyl, tetrahydrofuran-2-ylethyl, and indol-2-ylpropyl.

[0098] As used herein, the term "heteroarylalkyl" refers to an alkyl group, as defined herein, wherein a hydrogen or carbon bond of the alkyl group is replaced with a bond to a heteroaryl group, as defined herein.

[0099] As used herein, the term "heterocyclylalkyl" refers to an alkyl group as defined herein in which a hydrogen or carbon bond of the alkyl group as defined herein is replaced by a bond to a heterocyclyl group as defined herein. Representative heterocyclylalkyl groups include, but are not limited to, furan-2-ylmethyl, furan-3-ylmethyl, pyridin-3-ylmethyl, tetrahydrofuran-2-ylethyl, and indol-2-ylpropyl.

[0100] As used herein, the term "heterocyclyl" refers to aromatic and non-aromatic ring compounds containing three or more ring members, one or more of which is a heteroatom, such as, but not limited to, N, O, and S. Thus, a heterocyclyl group can be a cycloheteroalkyl or heteroaryl group, or, if polycyclic, any combination thereof. In some embodiments, a heterocyclyl group includes 3 to about 20 ring members, while other such groups have 3 to about 15 ring members. A heterocyclyl group designated as a C2-heterocyclyl group can be a 5-ring ring with two carbon atoms and three heteroatoms, a 6-ring ring with two carbon atoms and four heteroatoms, and so on. Similarly, a C4-heterocyclyl group can be a 5-ring ring with one heteroatom, a 6-ring ring with two heteroatoms, and so on. The number of carbon atoms plus the number of heteroatoms equals the total number of ring atoms. A heterocyclyl ring can also contain one or more double bonds. A heteroaryl ring is an embodiment of a heterocyclyl group. The phrase "heterocyclyl" includes fused ring species, including those containing fused aromatic and non-aromatic groups. For example, both a dioxolanyl ring and a benzodioxolanyl ring system (methylenedioxyphenyl ring system) are heterocyclyl groups within the meaning herein. The phrase also includes polycyclic ring systems containing heteroatoms, such as, but not limited to, quinuclidine. A heterocyclyl group may be unsubstituted or substituted as discussed herein. Heterocyclyl groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, thienyl, benzothienyl, benzofuranyl, dihydrobenzofuranyl, indolyl, dihydroindolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thiazolyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, quinoxalinyl, and quinazolinyl. Representative substituted heterocyclyl groups may be monosubstituted or substituted more than once, such as, but not limited to, piperidinyl or quinoline, which are 2, 3, 4, 5, or 6 substituted or disubstituted with groups such as those listed herein.

[0101] As used herein, the term "hydrocarbon" or "hydrocarbyl" refers to a molecule or functional group containing carbon and hydrogen atoms. The term may also refer to a molecule or functional group that typically contains both carbon and hydrogen atoms, but in which all hydrogen atoms are replaced by other functional groups. A hydrocarbyl group may be represented as (C a -C b )alkyl, wherein a and b are integers and mean any one of a to b carbon number. For example, (C1-C4)alkyl means that the alkyl group may be methyl (C1), ethyl (C2), propyl (C3) or butyl (C4), and (C0-C b ) alkyl means that in certain embodiments no alkyl groups are present.

[0102] As used herein, the term "IMes" refers to 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene.

[0103] As used herein, the term "ImPy" refers to imidazo[1,5-a]pyridine.

[0104] As used herein, the term "IPr" refers to 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene.

[0105] As used herein, the term "IPr*" refers to 1,3-bis((2,6-(bisbenzhydryl))-4-methylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene.

[0106] Unless the context clearly indicates otherwise, the term "independently selected from" as used herein means that the groups referred to are the same, different, or a mixture thereof. Therefore, under this definition, the phrase "X 1 、X 2 and X 3 independently selected from noble gases" would include the case where, for example, X 1 、X 2 and X 3 are all the same; among them X 1 、X 2 and X 3 are all different; among them X 1 and X 2 Same but X 3 different; and other similar arrangements.

[0107] As used herein, the term "Lewis acid" refers to a chemical species having an empty orbital that is capable of accepting a non-bonding electron pair from a species having a filled orbital containing an electron pair (ie, a Lewis base).

[0108] As used herein, the term "lithium amide" refers to the lithium salt of an anionic amine of the formula N(R)(R), wherein each R is independently selected from H, C1-C 12 Alkyl and Si(C1-C 12 alkyl) 3. Non-limiting examples of lithium amides include lithium diisopropylamide (LDA) and lithium hexamethylsiliconnitride (LiHMDS).

[0109] As used herein, the term "[M(#)X]" or "[M(NHC)X]" indicates an N-heterocyclic carbene (NHC) complex comprising a metal (M) (e.g., Au, Pd, Ag, Cu, and Rh), an anionic counterion (X) (e.g., Cl), and an NHC derived from an imidazolium salt (i.e., NHC or Compound #). Additional terms may be included to indicate other ligands and / or counterions. In such compounds, the compound number or name provided for the NHC may correspond to an imidazolium salt, however, the catalyst complex includes a carbene derived from the indicated imidazolium salt complexed with the indicated metal.

[0110] As used herein, the term "monovalent" refers to a substituent that is attached to the molecule being substituted via a single bond. When a substituent is monovalent, for example, F or Cl, the substituent is bonded to the atom it replaces via a single bond.

[0111] As used herein, the term "neutral ligand" or "ligand" refers to a ligand that has no net charge before or after binding to a metal center. Non-limiting examples of neutral ligands include olefins (e.g., cyclooctadiene), CO, amines (e.g., NMe), phosphines (e.g., PPh), and pyridyl ligands, in which coordination occurs via the nitrogen lone pair of the pyridyl group.

[0112] As used herein, the term "nitrile" refers to an organic compound containing a cyano group (C≡N).

[0113] As used herein, the term "organic group" refers to any functional group containing carbon. Examples can include groups containing oxygen, such as alkoxy, aryloxy, aralkyloxy, oxo (carbonyl) groups, carboxyl groups (including carboxylic acids, carboxylates, and carboxyl esters); groups containing sulfur, such as alkyl and aryl sulfide groups; and groups containing other heteroatoms. Non-limiting examples of organic groups include OR, OOR, OC(O)N(R)2, CN, CF3, OCF3, R, C(O), methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, S02R, SO2N(R)2, S03R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2) 0-2 N(R)C(O)R、(CH2) 0-2N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(=NH)N(R)2, C(O)N(OR)R, C(=NOR)R, and substituted or unsubstituted (C1-C 100 ) hydrocarbyl, wherein R can be hydrogen (in instances including other carbon atoms) or a carbon-based moiety, and wherein the carbon-based moiety can be substituted or unsubstituted.

[0114] As used herein, the term "protic solvent" refers to a solvent having a hydrogen atom bonded to a heteroatom (such as O, N, or S) such that H + Unstable. Non-limiting examples of protic solvents include methanol, ethanol, isopropanol, acetic acid, water, n-butanol, and formic acid. In contrast, as used herein, "aprotic solvent" refers to a solvent that lacks dissociable hydrogen ions (i.e., is non-acidic) to a considerable extent. Non-limiting examples of aprotic solvents include ethyl acetate (EtOAc), diethyl ether (Et2O), tetrahydrofuran (THF), dimethylformamide (DMF), and 1,4-dioxane.

[0115] As used herein, the term "room temperature" refers to a temperature of about 15°C to 28°C.

[0116] As used herein, the term "solvent" refers to a liquid that can dissolve solids, liquids, or gases. Non-limiting examples of solvents are silicones, organic compounds, water, alcohols, ionic liquids, and supercritical fluids.

[0117] As used herein, the term "substantially" refers to a majority or majority, such as at least about 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or at least about 99.999% or more, or 100%. As used herein, the term "substantially free" may mean free of or having an insignificant amount such that the amount of material present does not affect the material properties of the composition containing the material, such that the composition is from about 0 wt% to about 5 wt% of the material, or from about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4%, 3.5%, 3%, 2.5%, 2%, 1.5%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.01%, or about 0.001 wt% or less of the material. The term "substantially free" can mean having an insignificant amount such that the composition is from about 0 wt% to about 5 wt% of the material, or from about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equal to or greater than about 4.5 wt%, 4%, 3.5%, 3%, 2.5%, 2%, 1.5%, 1%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.01% or about 0.001 wt% or less, or about 0 wt% of the material.

[0118] As used herein in conjunction with a molecule or organic group as defined herein, the term "substituted" refers to a state in which one or more hydrogen atoms contained therein are replaced by one or more non-hydrogen atoms. As used herein, the term "functional group" or "substituent" refers to a group that can be or is substituted onto a molecule or organic group. Examples of substituents or functional groups include, but are not limited to, halogens (e.g., F, Cl, Br, and I); oxygen atoms in groups such as hydroxyl, alkoxy, aryloxy, aralkyloxy, oxo (carbonyl) groups, carboxyl groups (including carboxylic acids, carboxylates, and carboxylates); sulfur atoms in groups such as thiol groups, alkyl and aryl sulfide groups, sulfoxide groups, sulfone groups, sulfonyl groups, and sulfonamide groups; nitrogen atoms in groups such as amines, hydroxylamines, nitriles, nitro groups, N-oxides, hydrazides, azides, and enamines; and other heteroatoms in various other groups. Non-limiting examples of substituents that may be bonded to the substituted carbon (or other) atom include F, Cl, Br, I, OR, OC(O)N(R)2, CN, NO, NO2, ONO2, azido, CF3, OCF3, R, O(oxo), S(thiocarbonyl), C(O), S(O), methylenedioxy, ethylenedioxy, N(R)2, SR, SOR, S02R, S02N(R)2, S03R, C(O)R, C(O)C(O)R, C(O)CH2C(O)R, C(S)R, C(O)OR, OC(O)R, C(O)N(R)2, OC(O)N(R)2, C(S)N(R)2, (CH2) 0-2 N(R)C(O)R、(CH2) 0-2 N(R)N(R)2, N(R)N(R)C(O)R, N(R)N(R)C(O)OR, N(R)N(R)CON(R)2, N(R)SO2R, N(R)SO2N(R)2, N(R)C(O)OR, N(R)C(O)R, N(R)C(S)R, N(R)C(O)N(R)2, N(R)C(S)N(R)2, N(COR)COR, N(OR)R, C(═NH)N(R)2, C(O)N(OR)R, and C(═NOR)R, wherein R can be hydrogen or a carbon-based moiety; for example, R can be hydrogen, (C1-C 100 ) hydrocarbon, alkyl, acyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroarylalkyl; or wherein two R groups bonded to a nitrogen atom or to adjacent nitrogen atoms can, together with one or more nitrogen atoms, form a heterocyclyl.

[0119] Preparation of compounds

[0120] The compounds described herein may have one or more stereocenters, and each stereocenter may exist independently in the (R) or (S) configuration. In certain embodiments, the compounds described herein exist in optically active or racemic forms. It should be understood that the compounds described herein encompass racemic, optically active, regioisomeric, and stereoisomeric forms or combinations thereof having therapeutically useful properties as described herein. The preparation of optically active forms is achieved in any suitable manner, including (by way of non-limiting example) by resolving the racemic form with recrystallization techniques, synthesizing from optically active starting materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. In certain embodiments, a mixture of one or more isomers is utilized as a therapeutic compound described herein. In other embodiments, the compounds described herein contain one or more chiral centers. These compounds are prepared by any means including stereoselective synthesis, enantioselective synthesis, and / or separation of a mixture of enantiomers and / or diastereomers. The separation of the compound and its isomers is achieved by any means including (by way of non-limiting example) chemical methods, enzymatic methods, fractional crystallization, distillation, and chromatography.

[0121] The methods and formulations described herein include the use of N-oxides (if appropriate), crystalline forms (also referred to as polymorphs), solvates, amorphous phases, and / or pharmaceutically acceptable salts of compounds having the structure of any one or more of the compounds described herein, as well as metabolites and active metabolites of the same type of activity of these compounds. Solvates include water, ether (e.g., tetrahydrofuran, methyl tert-butyl ether) or alcohol (e.g., ethanol) solvates, acetates, and the like. In certain embodiments, the compounds described herein exist in a form solvated with a pharmaceutically acceptable solvent such as water and ethanol. In other embodiments, the compounds described herein exist in a non-solvated form.

[0122] In certain embodiments, one or more compounds described herein may exist as tautomers. All tautomers are included within the scope of the compounds presented herein.

[0123] In certain embodiments, the compounds described herein are prepared as prodrugs. A "prodrug" refers to an agent that is converted into the original drug in vivo. In certain embodiments, after in vivo administration, the prodrug is chemically converted to the biologically, pharmaceutically, or therapeutically active form of the compound. In other embodiments, the prodrug is enzymatically metabolized to the biologically, pharmaceutically, or therapeutically active form of the compound through one or more steps or processes.

[0124] In certain embodiments, sites on the aromatic ring portion of one or more compounds described herein are susceptible to various metabolic reactions. Incorporation of appropriate substituents on the aromatic ring structure can reduce, minimize, or eliminate such metabolic pathways. In certain embodiments, by way of example only, suitable substituents for reducing or eliminating the susceptibility of the aromatic ring to metabolic reactions are deuterium, halogen, or alkyl.

[0125] The compounds described herein also include isotopically labeled compounds, wherein one or more atoms are replaced by an atom having the same atomic number but an atomic mass or mass number different from the atomic mass or mass number usually found in nature. Examples of suitable isotopes for inclusion in the compounds described herein include, but are not limited to 2 H. 3 H. 11 C. 13 C. 14 C. 36 Cl, 18 F. 123 I. 125 I. 13 N. 15 N. 15 O. 17 O. 18 O. 32 P and 35 In certain embodiments, isotope-labeled compounds can be used for drug and / or substrate tissue distribution studies. In other embodiments, substitution with heavier isotopes (such as deuterium) provides greater metabolic stability (e.g., extending half-life in vivo or reducing dosage requirements). In yet other embodiments, substitution with positron-emitting isotopes (such as 11 C. 18 F. 15 O and 13 N) substitution can be used in positron emission tomography (PET) studies to examine substrate receptor occupancy. Isotopically labeled compounds are prepared by any suitable method or by using an appropriate isotopically labeled reagent in place of the non-labeled reagent otherwise employed.

[0126] In certain embodiments, the compounds described herein are labeled by other means including, but not limited to, the use of chromophores or fluorescent moieties, bioluminescent labels, or chemiluminescent labels.

[0127] The compounds described herein and other related compounds having various substituents are synthesized using the techniques and materials described herein and as described, for example, in Fieser and Fieser, Reagents for Organic Synthesis, Vols. 1-17 (John Wiley and Sons, 1991); Rodd, Chemistry of Carbon Compounds, Vols. 1-5 and Supplements (Elsevier Science Publishers, 1989); Organic Reactions, Vols. 1-40 (John Wiley and Sons, 1991); Larock, Comprehensive Organic Transformations (VCH Publishers Inc., 1989); March, Advanced Organic Chemistry 4th Edition, (Wiley 1992); Carey and Sundberg, Advanced Organic Chemistry 4th Edition, Vols. A and B (Plenum 2000, 2001); and Green and Wuts, Protective Groups in Organic Synthesis 3rd Edition, (Wiley 1999) (each of which is incorporated by reference for this disclosure). The general methods for preparing the compounds as described herein are modified by using appropriate reagents and conditions to introduce the various moieties found in the formulae as provided herein.

[0128] The compounds described herein are synthesized using any suitable procedure starting from compounds available from commercial sources, or are prepared using the procedures described herein.

[0129] In certain embodiments, reactive functional groups such as hydroxyl, amino, imino, sulfenyl or carboxyl are protected to prevent them from unnecessarily participating in the reaction. Protective groups are used to block some or all of the reactive moieties and prevent such groups from participating in chemical reactions until the protective group is removed. In other embodiments, each protective group can be removed by different means. Protective groups that are cut under completely different reaction conditions satisfy the requirement of difference removal.

[0130] In certain embodiments, protecting groups are removed by acid, base, reducing conditions (e.g., hydrogenolysis) and / or oxidizing conditions. Groups such as trityl, dimethoxytrityl, acetal and tert-butyldimethylsilyl are unstable to acid and are used to protect carboxyl and hydroxyl reactive moieties in the presence of amino groups protected by Cbz groups (removable by hydrogenolysis) and Fmoc groups (unstable to base). In the presence of amines blocked with acid-labile groups (e.g., tert-butyl carbamate) or with carbamates that are stable to both acid and base but can be removed by hydrolysis, carboxylic acid and hydroxyl reactive moieties are blocked with base-labile groups (e.g., but not limited to methyl, ethyl and acetyl).

[0131] In certain embodiments, carboxylic acid and hydroxyl reactive moieties are blocked with hydrolytically removable protecting groups (e.g., benzyl), while amine groups capable of hydrogen bonding with acids are blocked with base labile groups (e.g., Fmoc). Carboxylic acid reactive moieties are protected by conversion to simple ester compounds as exemplified herein (including conversion to alkyl esters), or are blocked with oxidatively removable protecting groups (e.g., 2,4-dimethoxybenzyl), while coexisting amino groups are blocked with silylcarbamates that are labile to fluoride.

[0132] Allyl blocking group is useful in the presence of acid blocking group and base blocking group, because the former is stable and is removed by metal or π acid catalyst subsequently.For example, in the presence of the unstable tert-butyl carbamate of acid or the unstable acetamine blocking group of base, the carboxylic acid of allyl blocking is deprotected with palladium catalyzed reaction.Another kind of blocking group is the resin for compound or intermediate attachment.As long as residue is attached on the resin, the functional group will be blocked and do not react.Once released from the resin, the functional group can react.

[0133] Other protecting groups, together with detailed descriptions of techniques suitable for the creation of protecting groups and their removal, are described in Greene and Wuts, Protective Groups in Organic Synthesis, 3rd ed., John Wiley & Sons, New York, NY, 1999; and Kocienski, Protective Groups, Thieme Verlag, New York, NY, 1994, which are incorporated herein by reference for this disclosure.

[0134] The compounds of the present disclosure can be prepared by the general schemes described herein using synthetic methods known to those skilled in the art.The following examples illustrate non-limiting embodiments of one or more compounds described herein and their preparation.

[0135] In certain illustrative embodiments, the N-heterocyclic carbene ligands of the present disclosure are prepared according to Schemes 1-2.

[0136] In certain embodiments, the N-heterocyclic carbene ligands are prepared as described in Scheme 1 (Method A), which utilizes a Pd-catalyzed Suzuki cross-coupling of arylboronic acid (1-1) and 1-2, followed by catalysis under standard conditions (i.e., (CHO) 8-100 and HCl) and condensed with amines and cyclized to form imidazolium.

[0137] In certain embodiments, the N-heterocyclic carbene ligands are prepared as described in Scheme 2 (Method B), which utilizes Ni-catalyzed Kumada cross-coupling of 1-6 and aryl magnesium halide 1-8 to provide 1-9, followed by 1-9 under standard conditions (i.e., (CHO) 8-100 and HCl) with an amine and cyclize to form an imidazolium. In certain embodiments, the acetal or ketal of 1-9 undergoes hydrolysis during the process under acidic reaction conditions (including but not limited to HCl in toluene at 100°C). In addition, Pd-catalyzed Negishi cross-coupling has been developed for the synthesis of sterically demanding C5-alkyl-substituted ligands containing imidazo[1,5-a]pyridine.

[0138] Solution 1.

[0139]

[0140] Option 2.

[0141]

[0142] In certain illustrative embodiments, the N-heterocyclic carbene (NHC) complexes of the present disclosure are prepared from the corresponding NHC ligands according to Schemes 3-6, wherein T 1 、T 2 、T 3 、R 1a 、R 1b 、R 1c 、R 2 、R 3 、R 4a 、R 4b 、R 4c 、R 4d 、R 4e , X and X 1 is as defined within the scope of this disclosure.

[0143] Option 3.

[0144]

[0145] Solution 4.

[0146]

[0147] Option 5.

[0148]

[0149] Option 6.

[0150]

[0151] Compound

[0152] In one aspect, the present disclosure provides compounds of formula (I):

[0153]

[0154] in:

[0155] T 1 Is N or CR 1a ;

[0156] T 2 Is N or CR 1b ;

[0157] T 3 Is N or CR 1c ;

[0158] R 1a 、R 1b and R 1c Each is independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0159] where R 1a 、R 1b and R 1c Each optional substituent in each of is independently selected from halogen,

[0160] C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group,

[0161] Among them, R 1a 、R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 Heterocyclic group

[0162] or optionally substituted C6-C 10 aryl;

[0163] R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 heterocyclic group;

[0164] R 3 Selected from optionally substituted C6-C 10 aryl, optionally substituted C2-C8 heteroaryl and optionally substituted C3-C8 cycloalkyl,

[0165] where R 3 Each optional substituent is independently selected from at least one of the following: H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、

[0166] N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、

[0167] S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C 12 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0168] wherein the C1-C6 alkyl, C3-C8 cycloalkyl, C2-C12 Heterocyclyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl are each optionally substituted with at least one substituent selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0169] R 4 Selected from optionally substituted C3-C 12 Cycloalkyl and phenyl substituted by at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, phenyl and N(R A )(R B ),

[0170] wherein the C3-C 12 Each optional substituent in the cycloalkyl group is at least one selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0171] X is the counter anion;

[0172] R A and R B Each independently selected from H, C1-C6 alkyl, C1-C3 haloalkyl, C2-C6 alkenyl, benzyl, naphthyl, C4-C 10 Heteroaryl and phenyl, where R A and R B Each substituent in is optionally substituted with at least one substituent selected from the group consisting of CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl and halogen.

[0173] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 is CH, and R 2 is H, and if R 4 is 2,4,6-triisopropylphenyl, then R 3 Not 2,6-diisopropylphenyl, 2,4,6-trimethylphenyl, 2-methylphenyl or 2,6-diethyl-4-methylphenyl.

[0174] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3is CH, and R 2 is H, and if R 4 is 2,4,6-trimethylphenyl, then R 3 Not 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, adamantyl, 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl, or (2-(2-methoxyethoxy)ethoxy)phenyl.

[0175] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 is CH, and R 2 is H, and if R 4 is 2-methylphenyl, then R 3 Not 2,6-diisopropylphenyl.

[0176] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 is CH, and R 2 is H, and if R 4 is 4-tert-butyl-2-pyridyl, then R 3 Not 2,6-diisopropylphenyl.

[0177] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 is CH, and R 2 is H, and if R 4 is 5-tetrahydroisoquinolinyl, then R 3 Not 2,6-diisopropylphenyl.

[0178] In certain embodiments, T 1 It's CR 1a In certain embodiments, T 2 It's CR 1b In certain embodiments, T 3 It's CR 1c .

[0179] In certain embodiments, T 1 It's CR 1a , T 2 It's CR 1b , and T 3 It's CR 1c In certain embodiments, T 1 It is N, T 2 It's CR 1b , and T 3 It's CR1c In certain embodiments, T 1 It's CR 1a , T 2 is N, and T 3 It's CR 1c In certain embodiments, T 1 It's CR 1a , T 2 It's CR 1b , and T 3 is N. In certain embodiments, T 1 It is N, T 2 is N, and T 3 It's CR 1c In certain embodiments, T 1 It is N, T 2 It's CR 1b , and T 3 is N. In certain embodiments, T 1 It's CR 1a , T 2 is N, and T 3 It's N.

[0180] In certain embodiments, R 1a 、R 1b and R 1c At least one of is H. In certain embodiments, R 1a 、R 1b and R 1c At least two of are H. In certain embodiments, R 1a 、R 1b and R 1c Each of them is H.

[0181] In certain embodiments, R 2 It’s H.

[0182] In certain embodiments, R 3 yes:

[0183]

[0184] in:

[0185] R 3a 、R 3b 、R 3c 、R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0186] where R 3a 、R 3b、R 3c 、R 3d and R 3e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

[0187] In certain embodiments, R 3a is H. In certain embodiments, R 3a In certain embodiments, R 3a In certain embodiments, R 3a In certain embodiments, R 3a In certain embodiments, R 3a It's fluorine.

[0188] In certain embodiments, R 3b is H. In certain embodiments, R 3b In certain embodiments, R 3b In certain embodiments, R 3b In certain embodiments, R 3b In certain embodiments, R 3b It's fluorine.

[0189] In certain embodiments, R 3c is H. In certain embodiments, R 3c In certain embodiments, R 3c In certain embodiments, R 3c In certain embodiments, R 3c In certain embodiments, R 3c It's fluorine.

[0190] In certain embodiments, R 3d is H. In certain embodiments, R 3d In certain embodiments, R 3d In certain embodiments, R 3d In certain embodiments, R 3d In certain embodiments, R 3d It's fluorine.

[0191] In certain embodiments, R 3e is H. In certain embodiments, R 3e In certain embodiments, R3e In certain embodiments, R 3e In certain embodiments, R 3e In certain embodiments, R 3e It's fluorine.

[0192] In certain embodiments, R 3b and R 3d are each independently H. In certain embodiments, R 3b 、R 3c and R 3d Each independently is H.

[0193] In certain embodiments, R 3a and R 3e In certain embodiments, R 3a 、R 3c and R 3e are the same.

[0194] In certain embodiments, R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b 、R 3c and R 3d is H. In certain embodiments, R 3a 、R 3c and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b and R 3d is H. In certain embodiments, R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, R 3c is selected from halogen and C1-C6 alkoxy, and R 3b and R 3d It’s H.

[0195] In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, RR 3 It is cyclohexyl.

[0196] In certain embodiments, R 4 yes:

[0197]

[0198] in:

[0199] R 4a 、R 4b 、R 4c 、R 4d and R 4e are each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0200] where R 4a 、R 4b 、R 4c 、R 4d and R 4e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

[0201] In certain embodiments, R 4a is H. In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a It is dimethylamino.

[0202] In certain embodiments, R 4b is H. In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b It is dimethylamino.

[0203] In certain embodiments, R 4c is H. In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c It is dimethylamino.

[0204] In certain embodiments, R 4d is H. In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d It is dimethylamino.

[0205] In certain embodiments, R 4e is H. In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R4e In certain embodiments, R 4e It is dimethylamino.

[0206] In certain embodiments, R 4b 、R 4c 、R 4d and R 4e are each independently H. In certain embodiments, R 4b 、R 4c and R 4d are each independently H. In certain embodiments, R 4a 、R 4c and R 4e are each independently H. In certain embodiments, R 4a 、R 4b 、R 4c 、R 4d and R 4e Neither is H.

[0207] In certain embodiments, R 4a and R 4e In certain embodiments, R 4b and R 4d In certain embodiments, R 4a 、R 4c and R 4e In certain embodiments, R 4a 、R 4b 、R 4c 、R 4d and R 4e are the same.

[0208] In certain embodiments, R 4a is selected from C1-C6 alkyl and N(C1-C6 alkyl)2, and R 4b 、R 4c 、R 4d and R 4e are each independently H. In certain embodiments, R 4a and R 4e are each independently C1-C6 alkyl, and R 4b 、R 4c and R 4d are each independently H. In certain embodiments, R 4a and R 4e are each independently a C1-C6 alkoxy group, and R 4b 、R 4c and R 4d are each independently H. In certain embodiments, R 4b and R4d are each independently C1-C6 alkyl or phenyl, and R 4a 、R 4c and R 4e are each independently H. In certain embodiments, R 4a 、R 4c and R 4e are each independently C1-C6 alkyl or C3-C8 cycloalkyl, and R 4b and R 4d are each independently H. In certain embodiments, R 4a 、R 4c and R 4e are each independently a C1-C6 alkoxy group, and R 4b and R 4d are each independently H. In certain embodiments, R 4a 、R 4b 、R 4c 、R 4d and R 4e Each is independently a C1-C6 alkyl group.

[0209] In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R4 In certain embodiments, R 4 It is an adamantyl group.

[0210] In certain embodiments, X is selected from halogen, OS(=O)2R A 、OC(=O)R A 、N(C(=O)R A )2, tetracoordinate borate and hexacoordinate phosphorus. In certain embodiments, X is Cl.

[0211] In certain embodiments, the compound is selected from:

[0212] 5-(2,6-Dimethylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0213] 2-mesityl-5-(2,4,6-triethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0214] 2-(2,6-diisopropylphenyl)-5-(2,4,6-triethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0215] 2-(2,6-diisopropylphenyl)-5-(2,3,4,5,6-pentamethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0216] 2-mesityl-5-(2,4,6-tricyclohexylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0217] 2-(2,6-diisopropylphenyl)-5-(2,4,6-tricyclohexylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0218] 5-(2,6-diisopropylphenyl)-2-(2,6-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0219] 5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0220] 2,5-bis(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0221] 2-Cyclohexyl-5-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0222] 2-(2,6-diisopropylphenyl)-5-(2,6-dimethoxyphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0223] 2-(2,6-diisopropylphenyl)-5-(2,4,6-trimethoxyphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0224] 5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0225] 5-(2-(Dimethylamino)phenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0226] 2-(2,6-diisopropylphenyl)-5-(2-(dimethylamino)phenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0227] 2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0228] 2-(2,6-bis(diphenylmethyl)-4-methoxyphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0229] 2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0230] 2-(2,6-bis(benzhydryl)-4-fluorophenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0231] 5-Cyclohexyl-2-mesitylphenylimidazo[1,5-a]pyridin-2-ium chloride;

[0232] 5-cyclohexyl-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0233] 5-(adamantan-1-yl)-2-mesitylphenylimidazo[1,5-a]pyridin-2-ium chloride;

[0234] 5-(adamantan-1-yl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0235] 5-(3,5-dimethylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0236] 2-(2,6-diisopropylphenyl)-5-(3,5-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0237] 5-(3,5-di-tert-butylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0238] 5-(3,5-di-tert-butylphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0239] 5-([1,1':3',1"-terphenyl]-5'-yl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride;

[0240] 5-([1,1':3',1"-terphenyl]-5'-yl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride;

[0241] 5-(2-isopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; and

[0242] 2-(2,6-Diisopropylphenyl)-5-(2-isopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride.

[0243] In another aspect, the present disclosure provides compounds of formula (II):

[0244]

[0245] in:

[0246] M is a transition metal;

[0247] L is a ligand of M, wherein each occurrence of L may be the same or different;

[0248] Each occurrence of is a single bond or a double bond,

[0249] There is no more than one bonded C atom and N atom It is a double bond;

[0250] T 1 Is N or CR 1a ;

[0251] T 2 Is N or CR 1b ;

[0252] T 3 Is N or CR 1c ;

[0253] R 1a 、R 1b and R 1cEach is independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0254] where R 1a 、R 1b and R 1c Each optional substituent in each of is independently selected from halogen,

[0255] C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group,

[0256] Among them, R 1a 、R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 Heterocyclic group

[0257] or optionally substituted C6-C 10 aryl;

[0258] R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 heterocyclic group;

[0259] R 3 Selected from optionally substituted C6-C 10 aryl, optionally substituted C2-C8 heteroaryl and optionally substituted C3-C8 cycloalkyl,

[0260] where R 3Each optional substituent is independently selected from at least one of the following: H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、

[0261] N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、

[0262] S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C 12 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0263] wherein the C1-C6 alkyl, C3-C8 cycloalkyl, C2-C 12 Heterocyclyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl are each optionally substituted with at least one substituent selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0264] R 4 Selected from optionally substituted C3-C 12 Cycloalkyl and phenyl substituted by at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, phenyl and N(R A )(R B ),

[0265] wherein the C3-C 12 Each optional substituent in the cycloalkyl group is at least one selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0266] X is the counter anion;

[0267] R A and RB Each independently selected from H, C1-C6 alkyl, C1-C3 haloalkyl, C2-C6 alkenyl, benzyl, naphthyl, C4-C 10 Heteroaryl and phenyl, where R A and R B Each substituent in is optionally substituted with at least one substituent selected from the group consisting of CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, and halogen;

[0268] m is an integer selected from 0, 1, 2 and 3;

[0269] n is an integer selected from 0, 1 and 2.

[0270] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is selected from Cu, Ag and Au, and R 4 is 2,4,6-triisopropylphenyl, then R 3 Not 2,6-diisopropylphenyl or 2,4,6-trimethylphenyl.

[0271] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Cu, and R 4 is 2,4,6-trimethylphenyl, then R 3 Not 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, adamantyl, 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl, or (2-(2-methoxyethoxy)ethoxy)phenyl.

[0272] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Pd, R 4 is 2,4,6-trimethylphenyl, and L is 3-chloropyridyl or pyridyl, then R 3 Not 2,4,6-trimethylphenyl or 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl.

[0273] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 It is CH, R2 is H, M is Pd, R 4 is 2,4,6-triisopropylphenyl, and X is an allyl anion (ie, vinylmethanide), then R 3 Not 2,4,6-trimethylphenyl.

[0274] In certain embodiments, if T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Au, and R 4 is 5-tetrahydroisoquinolinyl, then R 3 Not 2,6-diisopropylphenyl.

[0275] In certain embodiments, T 1 It's CR 1a In certain embodiments, T 2 It's CR 1b In certain embodiments, T 3 It's CR 1c .

[0276] In certain embodiments, T 1 It's CR 1a , T 2 It's CR 1b , and T 3 It's CR 1c In certain embodiments, T 1 It is N, T 2 It's CR 1b , and T 3 It's CR 1c In certain embodiments, T 1 It's CR 1a , T 2 is N, and T 3 It's CR 1c In certain embodiments, T 1 It's CR 1a , T 2 It's CR 1b , and T 3 is N. In certain embodiments, T 1 It is N, T 2 is N, and T 3 It's CR 1c In certain embodiments, T 1 It is N, T 2 It's CR 1b , and T 3 is N. In certain embodiments, T 1 It's CR1a , T 2 is N, and T 3 It's N.

[0277] In certain embodiments, R 1a 、R 1b and R 1c At least one of is H. In certain embodiments, R 1a 、R 1b and R 1c At least two of are H. In certain embodiments, R 1a 、R 1b and R 1c Each of them is H.

[0278] In certain embodiments, R 2 It’s H.

[0279] In certain embodiments, R 3 yes:

[0280]

[0281] in:

[0282] R 3a 、R 3b 、R 3c 、R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0283] where R 3a 、R 3b 、R 3c 、R 3d and R 3e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

[0284] In certain embodiments, R 3a is H. In certain embodiments, R 3a In certain embodiments, R 3a In certain embodiments, R 3a In certain embodiments, R 3a In certain embodiments, R 3a It's fluorine.

[0285] In certain embodiments, R 3b is H. In certain embodiments, R 3b In certain embodiments, R 3b In certain embodiments, R 3b In certain embodiments, R 3b In certain embodiments, R 3b It's fluorine.

[0286] In certain embodiments, R 3c is H. In certain embodiments, R 3c In certain embodiments, R 3c In certain embodiments, R 3c In certain embodiments, R 3c In certain embodiments, R 3c It's fluorine.

[0287] In certain embodiments, R 3d is H. In certain embodiments, R 3d In certain embodiments, R 3d In certain embodiments, R 3d In certain embodiments, R 3d In certain embodiments, R 3d It's fluorine.

[0288] In certain embodiments, R 3e is H. In certain embodiments, R 3e In certain embodiments, R 3e In certain embodiments, R 3e In certain embodiments, R 3e In certain embodiments, R 3e It's fluorine.

[0289] In certain embodiments, R 3b and R 3d are each independently H. In certain embodiments, R 3b 、R 3c and R 3d Each independently is H.

[0290] In certain embodiments, R 3a and R 3e In certain embodiments, R 3a 、R 3c and R 3e are the same.

[0291] In certain embodiments, R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b 、R 3c and R 3d is H. In certain embodiments, R 3a 、R 3c and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b and R 3d is H. In certain embodiments, R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, R 3c is selected from halogen and C1-C6 alkoxy, and R 3b and R 3d It’s H.

[0292] In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, R 3 yes In certain embodiments, RR 3 It is cyclohexyl.

[0293] In certain embodiments, R 4 yes:

[0294]

[0295] in:

[0296] R 4a 、R 4b 、R 4c 、R 4d and R 4e are each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0297] where R 4a 、R4b 、R 4c 、R 4d and R 4e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

[0298] In certain embodiments, R 4a is H. In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a In certain embodiments, R 4a It is dimethylamino.

[0299] In certain embodiments, R 4b is H. In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b In certain embodiments, R 4b It is dimethylamino.

[0300] In certain embodiments, R 4c is H. In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R 4c In certain embodiments, R4c In certain embodiments, R 4c In certain embodiments, R 4c It is dimethylamino.

[0301] In certain embodiments, R 4d is H. In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d In certain embodiments, R 4d It is dimethylamino.

[0302] In certain embodiments, R 4e is H. In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e In certain embodiments, R 4e It is dimethylamino.

[0303] In certain embodiments, R 4b 、R 4c 、R 4d and R 4e are each independently H. In certain embodiments, R 4b 、R 4c and R 4d are each independently H. In certain embodiments, R 4a 、R 4c and R 4e are each independently H. In certain embodiments, R 4a 、R 4b 、R 4c 、R 4d and R 4e Neither is H.

[0304] In certain embodiments, R 4a and R 4e In certain embodiments, R 4b and R 4d In certain embodiments, R 4a 、R 4c and R 4e In certain embodiments, R 4a 、R 4b 、R 4c 、R 4d and R 4e are the same.

[0305] In certain embodiments, R 4a is selected from C1-C6 alkyl and N(C1-C6 alkyl)2, and R 4b 、R 4c 、R 4d and R 4e are each independently H. In certain embodiments, R 4a and R 4e are each independently C1-C6 alkyl, and R 4b 、R 4c and R 4d are each independently H. In certain embodiments, R 4a and R 4e are each independently a C1-C6 alkoxy group, and R 4b 、R 4c and R 4d are each independently H. In certain embodiments, R 4b and R 4d are each independently C1-C6 alkyl or phenyl, and R 4a 、R 4c and R 4e are each independently H. In certain embodiments, R 4a 、R 4c and R 4e are each independently C1-C6 alkyl or C3-C8 cycloalkyl, and R 4b and R 4d are each independently H. In certain embodiments, R 4a 、R 4c and R 4e are each independently a C1-C6 alkoxy group, and R 4b and R 4d are each independently H. In certain embodiments, R 4a 、R 4b 、R 4c 、R4d and R 4e Each is independently a C1-C6 alkyl group.

[0306] In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 yes In certain embodiments, R 4 In certain embodiments, R 4 It is an adamantyl group.

[0307] In certain embodiments, X is selected from halogen, OS(=O)2R A 、OC(=O)R A 、N(C(=O)R A )2, tetracoordinate borate, hexacoordinate phosphorus, optionally substituted C6-C 10 Aryl and optionally substituted C2-C 10 Heteroaryl, wherein the C6-C 10 Each optional substituent in aryl and C2-C8 heteroaryl is independently selected from halogen, CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C3-C8 cycloalkyl, phenyl and C2-C8 heterocyclyl.

[0308] In certain embodiments, X is Cl. In certain embodiments, X is an allyl anion (i.e., vinylmethane). In certain embodiments, X is a tert-butylindenyl anion (i.e., 1-tert-butylinden-1-root and / or 3-tert-butylinden-1-root). In certain embodiments, X is an allylbenzene anion (i.e., 3-phenylpropylene-3-root and / or 1-phenylpropylene-3-root).

[0309] In certain embodiments, M is selected from Pd, Cu, Ag, Au, Ni, Pt, Co, Rh, Ir, Fe, Ru, and Os. In certain embodiments, M is Pd. In certain embodiments, M is Cu. In certain embodiments, M is Ag. In certain embodiments, M is Rh.

[0310] In certain embodiments, L is selected from carbon monoxide (CO), optionally substituted C2-C 12 olefins, and optionally substituted C5-C 12 Cycloalkene, optionally substituted benzylamine, optionally substituted C2-C8 heteroaryl, wherein the C2-C 12 Olefins, C5-C 12 Each optional substituent in cycloalkene, benzylamine and C2-C8 heteroaryl is independently selected from halogen, CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C3-C8 cycloalkyl, phenyl and C2-C8 heterocyclyl.

[0311] In certain embodiments, L is cyclooctadiene (COD). In certain embodiments, L is carbon monoxide (CO). In certain embodiments, L is pyridine. In certain embodiments, L is 3-chloropyridine.

[0312] In certain embodiments, the compound is selected from:

[0313] Cinnamyl[5-(2,6-diisopropylphenyl)-2-mesitylimidazo[1,5-a]pyridin-3-ylidene]palladium chloride;

[0314] Cinnamyl[2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0315] Cinnamyl[5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0316] 2-Dimethylaminomethylphenyl[2-(2,6-bis(benzhydryl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0317] 2-Acetamido-phenyl[2-(2,6-bis(benzhydryl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0318] Cinnamyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0319] Allyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0320] Cinnamyl[2-(2,6-diisopropylphenyl)-5-mesitylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0321] 1-tert-Butyl-indenyl[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0322] Cinnamyl[2-mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride;

[0323] Pyridinium[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride;

[0324] 3-Chloropyridinium[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride;

[0325] 3-Chloropyridinium[2-mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride;

[0326] (2,5-dimesityl imidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride;

[0327] (5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride;

[0328] (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride;

[0329] (2-(2,6-bis(benzhydryl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride;

[0330] (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride;

[0331] (5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride;

[0332] (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride;

[0333] (2-(2,6-bis(benzhydryl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride;

[0334] (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride;

[0335] (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride;

[0336] (2-(2,6-bis(benzhydryl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride;

[0337] (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride;

[0338] Cyclooctadiene[5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride;

[0339] Dicarbonyl[5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride;

[0340] Cyclooctadieno[2,5-dimesitylphenylimidazo[1,5-a]pyridin-2-ylidene]rhodium(I) chloride;

[0341] Dicarbonyl[2,5-dimesityl imidazo[1,5-a]pyridin-2-ylidene]rhodium(I) chloride;

[0342] Cyclooctadiene[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride;

[0343] Dicarbonyl[2-(2,6-bis(benzhydryl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride;

[0344] (5-(2,4,6-triethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride;

[0345] Cinnamyl(5-(2,4,6-triethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)palladium(II) chloride;

[0346] (5-(2,4,6-trimethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride;

[0347] (5-(2,6-diisopropylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; and

[0348] (5-(2,6-Diisopropylphenyl)-2-cyclohexyl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride.

[0349] Table 1. N-Heterocyclic Carbene (NHC) Ligands and Catalyst Complexes

[0350]

[0351]

[0352]

[0353]

[0354]

[0355]

[0356]

[0357]

[0358]

[0359]

[0360]

[0361]

[0362]

[0363]

[0364]

[0365] method

[0366] In one aspect, the present disclosure provides a method for promoting the reaction between a boronic acid and a nitroarene, the method comprising contacting the boronic acid and the nitroarene in the presence of a compound of the present disclosure and a base, and optionally in the presence of a phase transfer catalyst. In certain embodiments, the base is K3PO4. In certain embodiments, the method further comprises water. In certain embodiments, the phase transfer catalyst is TDA. In certain embodiments, the reaction occurs at a temperature of about 130°C. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is 1,4-dioxane.

[0367] In one aspect, the present disclosure provides a method for promoting the reaction between an alkyl sulfoxide and an aniline, the method comprising contacting the alkyl sulfoxide and the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is LiHMDS. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is THF. In certain embodiments, the reaction occurs at a temperature of about 100°C.

[0368] In one aspect, the present disclosure provides a method for promoting the reaction between a thiophenol and an aniline, the method comprising contacting the thiophenol and the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is LiHMDS. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is toluene. In certain embodiments, the reaction occurs at a temperature of about 130°C.

[0369] In one aspect, the present disclosure provides a method for promoting the reaction between an aryl halide and a hydrazine, the method comprising contacting the aryl halide and the hydrazine in the presence of a compound of the present disclosure and a Lewis acid to provide an aryl hydrazine. In certain embodiments, the Lewis acid is rubidium carbonate. In certain embodiments, the reaction is carried out in the presence of a solvent. In certain embodiments, the solvent is 1,4-dioxane. In certain embodiments, the hydrazine is hydrazine monohydrate. In certain embodiments, the reaction occurs at a temperature of about 100°C. In certain embodiments, the reaction further comprises contacting the aryl hydrazine and a 1,3-diketone to provide 1-phenylpyrazole. In certain embodiments, the 1,3-diketone is acetylacetone.

[0370] In one aspect, the present disclosure provides a method for promoting the reaction of an aryl methanesulfonate or aryl toluenesulfonate with boronic acid, the method comprising contacting the aryl methanesulfonate or aryl toluenesulfonate with the boronic acid in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is potassium phosphate. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is isopropanol. In certain embodiments, the reaction occurs at a temperature of about 130°C.

[0371] In one aspect, the present disclosure provides a method for promoting the reaction of an aryl methanesulfonate or aryl toluenesulfonate with aniline, the method comprising contacting the aryl methanesulfonate or aryl toluenesulfonate with the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is potassium phosphate. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is tert-amyl alcohol. In certain embodiments, the reaction occurs at a temperature of about 120°C.

[0372] In one aspect, the present disclosure provides a method for promoting the reaction between an arylsulfamate and a boronic acid, the method comprising contacting the arylsulfamate and the boronic acid in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is potassium phosphate. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is isopropanol. In certain embodiments, the reaction occurs at a temperature of about 130°C.

[0373] In one aspect, the present disclosure provides a method for promoting the reaction between an arylsulfamate and an aniline, the method comprising contacting the arylsulfamate and the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is potassium phosphate. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is tert-amyl alcohol. In certain embodiments, the reaction occurs at a temperature of about 120°C.

[0374] In one aspect, the present disclosure provides a method for promoting the reaction between an aryl halide and a hydroxide salt, the method comprising contacting the aryl halide and the hydroxide salt in the presence of a compound of the present disclosure. In certain embodiments, the hydroxide salt is cesium hydroxide. In certain embodiments, the cesium hydroxide is cesium hydroxide monohydrate. In certain embodiments, the reaction is carried out in the presence of a solvent. In certain embodiments, the solvent is 1,4-dioxane. In certain embodiments, the reaction occurs at a temperature of about 120°C. In certain embodiments, the aryl halide is an aryl chloride. In certain embodiments, the aryl halide is an aryl bromide.

[0375] In one aspect, the present disclosure provides a method for promoting the reaction between an aryl methyl sulfide and aniline, the method comprising contacting the aryl methyl sulfide and the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is NaHMDS. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is toluene. In certain embodiments, the reaction occurs at a temperature of about 100°C.

[0376] In one aspect, the present disclosure provides a method for promoting the reaction between an aryl sulfoxide and an aniline, the method comprising contacting the aryl sulfoxide and the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is LiHMDS. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is toluene. In certain embodiments, the reaction occurs at a temperature of about 80°C.

[0377] In one aspect, the present disclosure provides a method for promoting the reaction between an amine and an aryl chloride, the method comprising contacting the amine and the aryl chloride in the presence of a compound of the present disclosure and a base. In certain embodiments, the amine is aniline. In certain embodiments, the amine is a C2-C8 heterocyclic group containing at least one secondary nitrogen. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is cyclopentyl methyl ether. In certain embodiments, the reaction occurs at a temperature of about 60°C.

[0378] In one aspect, the present disclosure provides a method for promoting the reaction between an aryl chloride and a boronic acid, the method comprising contacting the aryl chloride and the boronic acid in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is NaOtBu. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is THF. In certain embodiments, the reaction occurs at a temperature of about 60°C.

[0379] In one aspect, the present disclosure provides a method for promoting the reaction between an aryl fluoride and an aniline, the method comprising contacting the aryl fluoride and the aniline in the presence of a compound of the present disclosure and a base. In certain embodiments, the base is LiHMDS. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is toluene. In certain embodiments, the reaction occurs at a temperature of about 130°C.

[0380] In one aspect, the present disclosure provides a method for promoting the reaction between an alkyne and an aniline, the method comprising contacting the alkyne and the aniline in the presence of a compound of the present disclosure and a reducing agent. In certain embodiments, the reducing agent is a silane (e.g., phenylsilane). In certain embodiments, the reaction occurs in the presence of a Lewis acid. In certain embodiments, the Lewis acid is [Ag(MeCN)2] + BARF - In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is toluene. In certain embodiments, the solvent is trifluorotoluene. In certain embodiments, the solvent further comprises water. In certain embodiments, the reaction occurs at a temperature of about 40°C.

[0381] In certain embodiments, at least one of the following applies:

[0382] (a) The boric acid is C6-C 10Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one borate or boronic acid moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0383] (b) the nitroaromatic hydrocarbon is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one NO2 moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0384] (c) the alkyl sulfoxide is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is partially substituted by at least one S(=O) (optionally substituted C1-C6 alkyl), and further optionally substituted by at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0385] (d) The aniline is C6-C 10Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one NH2 moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0386] (e) The thiophenol is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one thiol moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0387] (f) The aryl halide is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted by at least one halogen selected from Cl, Br and I, and is further optionally substituted by at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0388] (g) The aryl toluene sulfonate is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C10 The aryl or C2-C8 heteroaryl is substituted with at least one tosyloxy moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0389] (h) the aryl methanesulfonate is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one methanesulfonyloxy moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0390] (i) The aryl sulfamate is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one sulfamate moiety and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0391] (j) The aryl chloride is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10The aryl or C2-C8 heteroaryl is substituted with at least one Cl, and further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0392] (k) The aryl methyl sulfide is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one methylthio moiety (i.e., -SCH3), and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0393] (1) The aryl sulfoxide is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted by at least one substituent selected from the group consisting of S(=O) (optionally substituted C1-C6 alkyl), S(=O) (optionally substituted C6-C 10 aryl) and S(═O) (optionally substituted C2-C8 heteroaryl), and further optionally substituted by at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2;

[0394] (m) the amine is selected from N(optionally substituted C1-C6 alkyl)2, N(optionally substituted C1-C6 alkyl) (optionally substituted C6-C 10 Aryl), N (optionally substituted C6-C 10 aryl)2 and optionally substituted C2-C8 heterocycloalkyl, wherein the heterocycloalkyl contains at least one secondary amine;

[0395] (n) The aryl bromide is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one Br, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl), and C(=O)N(C1-C6 alkyl); and

[0396] (o) The aryl fluoride is C6-C 10 Aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one Br, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2.

[0397] In certain embodiments, the compounds of the present disclosure are compounds of formula (III):

[0398]

[0399] in:

[0400] M is a transition metal;

[0401] L is a ligand of M, wherein each occurrence of L may be the same or different;

[0402] Each occurrence of is a single bond or a double bond,

[0403] There is no more than one bonded C atom and N atom It is a double bond;

[0404] T 1 Is N or CR 1a ;

[0405] T 2 Is N or CR 1b ;

[0406] T 3 Is N or CR 1c ;

[0407] R 1a 、R 1b and R 1c Each is independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0408] where R 1a 、R 1b and R 1c Each optional substituent in each of is independently selected from halogen,

[0409] C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group,

[0410] Among them, R 1a 、R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12Cycloalkyl, optionally substituted C2-C 12 Heterocyclic group

[0411] or optionally substituted C6-C 10 aryl;

[0412] R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 heterocyclic group;

[0413] R 3 Selected from optionally substituted C6-C 10 aryl, optionally substituted C2-C8 heteroaryl and optionally substituted C3-C8 cycloalkyl,

[0414] where R 3 Each optional substituent is independently selected from at least one of the following: H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、

[0415] N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、

[0416] S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C 12 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0417] wherein the C1-C6 alkyl, C3-C8 cycloalkyl, C2-C 12 Heterocyclyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl are each optionally substituted with at least one substituent selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0418] R 4 Selected from optionally substituted C3-C 12Cycloalkyl and phenyl substituted by at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, phenyl and N(R A )(R B ),

[0419] wherein the C3-C 12 Each optional substituent in the cycloalkyl group is at least one selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl,

[0420] C2-C6 alkenyl, benzyl, phenyl and naphthyl and C2-C 12 heterocyclic group;

[0421] X is the counter anion;

[0422] R A and R B Each independently selected from H, C1-C6 alkyl, C1-C3 haloalkyl, C2-C6 alkenyl, benzyl, naphthyl, C4-C 10 Heteroaryl and phenyl, where R A and R B Each substituent in is optionally substituted with at least one substituent selected from the group consisting of CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, and halogen;

[0423] m is an integer selected from 0, 1, 2 and 3; and

[0424] n is an integer selected from 0, 1 and 2.

[0425] In certain embodiments, M in the compound of formula (III) is Pd. In certain embodiments, the compound of formula (III) has a concentration of about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mol%. In certain embodiments, the compound of formula (III) is selected from compounds 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50.

[0426] In certain embodiments, the compound of the present disclosure is a compound of formula (II). In certain embodiments, M in the compound of formula (II) is Pd. In certain embodiments, the compound of formula (II) has a concentration of about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 mol%.

[0427] In another aspect, the present disclosure provides a method for preparing a compound of formula (IV):

[0428]

[0429] in:

[0430] T 1 Is N or CR 1a ;

[0431] T 2 Is N or CR 1b ;

[0432] T 3 Is N or CR 1c ;

[0433] R 1a 、R 1b and R 1c each independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0434] where R 1a 、R 1b and R 1c Each optional substituent in each of is independently selected from halogen,

[0435] C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group,

[0436] Among them, R 1a 、R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 Heterocyclic group

[0437] or optionally substituted C6-C 10 aryl;

[0438] R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 heterocyclic group;

[0439] R 3a 、R 3b 、R3c 、R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0440] where R 3a 、R 3b 、R 3c 、R 3d and R 3e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkoxy

[0441] C2-C6 alkenyl, benzyl, phenyl and naphthyl and C2-C 12 heterocyclic group;

[0442] R 4a 、R 4b 、R 4c 、R 4d and R 4e are each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0443] where R 4a 、R 4b 、R 4c 、R 4d and R 4e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclyl; and

[0444] X is the counterion;

[0445] The method comprises causing (Z):

[0446]

[0447] With (Y):

[0448]

[0449] Contact in the presence of paraformaldehyde and acid.

[0450] In certain embodiments, Z is In certain embodiments, Z is In certain embodiments, Z is

[0451] In certain embodiments, the acid is HCl in 1,4-dioxane, such as, but not limited to, 4M HCl in 1,4-dioxane. In certain embodiments, the reaction occurs at a temperature of about 100° C. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is toluene.

[0452] In certain embodiments, (Z) is obtained by making (X):

[0453]

[0454] With (W):

[0455]

[0456] Prepared by reacting in the presence of a transition metal catalyst;

[0457] where X 1 and X 2 are each independently selected from Cl, Br and I.

[0458] In certain embodiments, W is

[0459] In certain embodiments, X 1 Is Cl. In certain embodiments, X 2 is Br. In certain embodiments, the transition metal catalyst is Ni(PCy3)Cl2. In certain embodiments, the reaction occurs in the presence of a solvent. In certain embodiments, the solvent is THF. In certain embodiments, the reaction occurs at a temperature of about 50°C.

[0460] In certain embodiments, T 1 It's CR 1a , T 2 It's CR 1b , and T 3 It's CR 1c In certain embodiments, T 1 It is N, T 2 It's CR 1b , and T 3 It's CR 1c In certain embodiments, T 1 It's CR 1a , T 2 is N, and T 3 It's CR 1c In certain embodiments, T 1 It's CR 1a , T2 It's CR 1b , and T 3 is N. In certain embodiments, T 1 It is N, T 2 is N, and T 3 It's CR 1c In certain embodiments, T 1 It is N, T 2 It's CR 1b , and T 3 is N. In certain embodiments, T 1 It's CR 1a , T 2 is N, and T 3 It's N.

[0461] Example

[0462] Various embodiments of the present application may be better understood by reference to the following examples which are provided by way of illustration.The scope of this application is not limited to the examples given herein.

[0463] Example 1: Synthesis of imidazo[1,5-α]pyridine N-heterocyclic carbene (NHC) ligand

[0464] General Procedure A: Suzuki Cross-coupling

[0465] Step 1: Suzuki cross-coupling

[0466]

[0467] 6-Bromopyridine-2-carboxaldehyde (930 mg, 5 mmol, 1 equivalent), arylboronic acid (Ar 1 A mixture of -B(OH)2) (6.5 mmol, 1.3 equiv.), Pd(PPh3)4 (289 mg, 0.25 mmol, 5 mol%) and K3PO4 (3.18 g, 15 mmol, 3 equiv.) in toluene (20 mL, 0.25 M) was heated at 100°C under argon for 12 h. After cooling, the organic layer was separated and the aqueous layer was extracted with ethyl acetate (50 mL x 2). The organic layers were combined and dried over Na2SO4. The solvent was removed in vacuo and the residue was chromatographed on silica gel eluting with ethyl acetate / hexane (1 / 20) to give the desired product.

[0468] Step 2: Synthesis of NHC salt

[0469]

[0470] To a mixture of the above-obtained pyridinecarboxaldehyde (1 mmol, 1 equiv), aniline (1 mmol, 1 equiv), paraformaldehyde (45 mg, 1.5 mmol, 1.5 equiv) in toluene (2 mL, 0.5 M) was added 4 M HCl in dioxane (0.5 ml, 2 mmol, 2 equiv). The mixture was then heated at 100° C. for 12 h. The solvent was removed under reduced pressure. The residue was chromatographed on silica gel, eluting with dichloromethane / methanol (50 / 1 to 30 / 1 to 15 / 1) to give the desired product.

[0471] General Procedure B: Kumada Cross-coupling

[0472] Step 1: 2-Bromo-6-(1,3-dioxolan-2-yl)pyridine

[0473]

[0474] A mixture of 6-bromopyridine-2-carboxaldehyde (18.6 g, 100 mmol, 1 equivalent), ethylene glycol (11.2 mL, 12.4 g, 200 mmol, 2 equivalents), p-toluenesulfonic acid monohydrate (1.72 g, 10 mmol, 10 mol%) and MgSO (12 g, 100 mmol, 1 equivalent) in toluene (100 mL) was heated at 100 ° C for 12 h. After cooling, an aqueous NaHCO solution was added to the reaction mixture. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL × 2). The combined organic layers were washed with brine and dried over Na SO. The solvent was removed in vacuo to obtain the product (21.9 g) as a colorless oil in a yield of 95%. 1 HNMR (500MHz, CDCl3) δ7.57 (t, J = 7.7Hz, 1H), 7.51–7.43 (m, 2H), 5.79 (s, 1H), 4.16–4.11 (m, 2H), 4.08–4.02 (m, 2H). 13 C NMR (125MHz, CDCl3) δ158.61,141.74,139.18,128.58,119.49,102.85,65.70.

[0475] Step 2: Kumada cross-coupling reaction

[0476]

[0477] Activated magnesium turnings (173 mg, 7.2 mmol, 1.44 eq) were suspended in anhydrous THF (10 mL). A solution of an aryl bromide (6 mmol, 1.2 eq) in anhydrous THF (5 mL) was slowly added to the mixture at ambient temperature. The Grignard reaction was initiated by the addition of catalytic 1,2-dibromoethane (50 μL). After the addition was complete, the reaction mixture was heated at 60°C for 2 h.

[0478] The above Grignard solution was slowly added to a well-stirred suspension of 2-bromo-6-(1,3-dioxolane-2-yl)pyridine (1.15 g, 5 mmol, 1.0 equiv) and Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) in anhydrous THF (10 mL) over 10 minutes. The resulting brown solution was heated at 50°C for 12 h, after which the mixture was poured onto an NH4Cl aqueous solution. The aqueous layer was extracted with ethyl acetate, and the combined organic extracts were washed with brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by flash chromatography on silica gel (hexane / ethyl acetate 10 / 1 to 6 / 1).

[0479] Step 3: Synthesis of NHC salt

[0480]

[0481] An oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with the above intermediate (2.0 mmol, 1.0 equiv), aniline (Ar 2 To the mixture was added 4-[ ...

[0482] Synthesis of intermediates

[0483] General Procedure A

[0484]

[0485] 6-(2,6-Dimethylphenyl)picolinaldehyde. Prepared according to step 1 in general procedure A, reaction of 6-bromopyridine-2-carboxaldehyde (930 mg, 5 mmol, 1 eq), 2,6-dimethylphenylboronic acid (975 mg, 6.5 mmol, 1.3 eq), Pd(PPh3)4 (289 mg, 0.25 mmol, 5 mol%) and K3PO4 (3.18 g, 15 mmol, 3 eq) in toluene (20 mL) gave the title compound (992 mg) as a colorless oil in 94% yield. 1 H NMR (500MHz, CDCl3) δ10.13 (s, 1H), 7.98–7.94 (m, 2H), 7.50–7.46 (m, 1H), 7.26–7.23 (m, 1H), 7.15 (d, J = 7.6Hz, 2H), 2.06 (s, 6H). 13 CNMR (125MHz, CDCl3) δ194.03,160.85,153.00,139.41,137.56,135.88,129.05,128.60,127.99,119.74,20.39.

[0486]

[0487] 6-(2,6-Dimethoxyphenyl)picolinaldehyde. Prepared according to step 1 in general procedure A, reaction of 6-bromopyridine-2-carboxaldehyde (1.86 g, 10 mmol, 1 eq), 2,6-dimethoxyphenylboronic acid (2.37 g, 13 mmol, 1.3 eq), Pd(PPh3)4 (578 mg, 0.25 mmol, 5 mol%) and K3PO4 (6.36 g, 15 mmol, 3 eq) in toluene (40 mL) gave the title compound (1.85 g) as a white solid in 76% yield. Spectral data matched literature values.

[0488]

[0489] 6-(2,4,6-Trimethoxyphenyl)picolinaldehyde. Prepared according to step 1 in general procedure A, reaction of 6-bromopyridine-2-carboxaldehyde (1.86 g, 10 mmol, 1 eq), 2,4,6-trimethoxyphenylboronic acid (2.75 g, 13 mmol, 1.3 eq), Pd(PPh3)4 (578 mg, 0.25 mmol, 5 mol%) and K3PO4 (6.36 g, 15 mmol, 3 eq) in toluene (40 mL) gave the title compound (1.83 g) as a white solid in 67% yield. 1H NMR (500MHz, CDCl3) δ10.14 (s, 1H), 7.92–7.83 (m, 2H), 7.51 (d, J = 7.5Hz, 1H), 6.23 (s, 2H), 3.87 (s, 4H), 3.72 (s, 6H). 13 CNMR (125MHz,CDCl3)δ194.43,161.97,158.98,155.60,152.79,136.71,131.33,119.58,111.24,91.14,56.06,55.62. HRMS for C 30 H 30 O8N2Na(2M + The calculated value of NH4Cl2 (Na) was 569.1894, and the measured value was 569.1921.

[0490]

[0491] 6-(3,5-Dimethylphenyl)picolinaldehyde. Prepared according to step 1 in general procedure A, reaction of 6-bromopyridine-2-carboxaldehyde (1.49 g, 8 mmol, 1 eq), 3,5-dimethylphenylboronic acid (1.56 g, 10.4 mmol), Pd(PPh3)4 (0.46 g, 0.4 mmol, 5 mol%) and K3PO4 (3.4 g, 16 mmol, 2 eq) in toluene (27 mL) gave the title compound (1.61 g, 95%) as a white solid. 1 H NMR (500MHz, CDCl3) δ10.18(s,1H),7.97–7.87(m,3H),7.69(s,2H),7.12(s,1H),2.43(s,6H). 13 C NMR (125 MHz, CDCl3) δ 194.17, 158.48, 152.84, 138.69, 138.28, 137.78, 131.47, 125.02, 124.79, 119.76, 21.58. Spectral data matched literature values.

[0492]

[0493] 6-(3,5-di-tert-butylphenyl)picolinaldehyde. Prepared according to step 1 in general procedure A, reaction of 6-bromopyridine-2-carboxaldehyde (0.56 g, 3 mmol, 1 eq), 3,5-di-tert-butylphenylboronic acid (0.92 g, 3.9 mmol, 1.3 eq), Pd(PPh3)4 (0.17 g, 0.15 mmol, 5 mol%) and K3PO4 (1.3 g, 6 mmol, 2 eq) in toluene (10 mL) gave the title compound (0.78 g, 88%) as a white solid. 1 H NMR (500MHz, CDCl3) δ10.14(s,1H),7.91–7.81(m,5H),7.52(s,1H),1.36(s,18H). 13 C NMR (125 MHz, CDCl3) δ 194.19, 159.25, 152.76, 151.51, 137.78, 137.66, 124.96, 123.95, 121.55, 119.42, 35.14, 31.60. HRMS for C 20 H 26 NO(M + The calculated value of H (H) was 296.2009, and the found value was 296.2028.

[0494]

[0495] 6-(2-Isopropylphenyl)picolinaldehyde. Prepared according to step 1 in general procedure A, reaction of 6-bromopyridine-2-carboxaldehyde (930 mg, 5 mmol, 1 eq), 2-isopropylphenylboronic acid (1.07 g, 6.5 mmol, 1.3 eq), Pd(PPh3)4 (289 mg, 0.25 mmol, 5 mol%) and K3PO4 (3.18 g, 15 mmol, 3 eq) in toluene (20 mL) gave the title compound (1.02 g) as a colorless oil in 91% yield. 1 H NMR(500MHz, CDCl3)δ10.13(s,1H),7.98–7.91(m,2H),7.61(dd,J=7.0,2.0Hz,1H),7.48–7.42(m ,2H),7.34(d,J=6.0Hz,1H),7.29(t,J=6.4Hz,1H),3.14(p,J=6.9Hz,1H),1.22(d,J=6.9Hz,6H). 13C NMR (125 MHz, CDCl3) δ 194.06, 161.21, 152.44, 146.90, 138.69, 137.32, 129.75, 129.34, 128.62, 126.19, 125.93, 119.55, 29.57, 24.28. HRMS for C 15 H 16 NO(M + The calculated value of H (H) was 226.1226, and the found value was 226.1203.

[0496] General Procedure B

[0497]

[0498] 2-(1,3-Dioxolan-2-yl)-6-(2,4,6-triethylphenyl)pyridine. Prepared according to step 2 in general procedure B, reaction of 2-bromo-1,3,5-triethylbenzene (1.45 g, 6 mmol, 1 eq), magnesium turnings (173 mg, 7.2 mmol, 1.44 eq), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine 6 (1.15 g, 5 mmol, 1.0 eq) in THF (10 mL) gave the title compound as a yellow oil in 92% yield (1.71 g). 1 H NMR (500MHz, CDCl3) δ7.80(t,J=7.7Hz,1H),7.54(d,J=7.8Hz,1H),7.28(d,J=7.6Hz,1H),6.97(s,2H),5.87(s,1H),4. 24–4.17(m,2H),4.10–4.05(m,2H),2.67–2.62(m,2H),2.36–2.25(m,4H),1.25(t,J=7.6Hz,3H),1.02(t,J=7.6Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 159.29, 156.76, 144.43, 142.05, 136.87, 126.21, 125.59, 125.56, 118.58, 104.30, 65.73, 28.96, 26.79, 15.83, 15.56. HRMS for C 20 H 29 N2O2(M + +NH4) was calculated to be 329.2224, and the measured value was 329.2167.

[0499]

[0500] 2-(1,3-Dioxolan-2-yl)-6-(2,3,4,5,6-pentamethylphenyl)pyridine. Prepared according to step 2 in general procedure B, reaction of 1-bromo-2,3,4,5,6-pentamethylbenzene (1.36 g, 6 mmol, 1 eq), magnesium turnings (173 mg, 7.2 mmol, 1.44 eq), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine (1.15 g, 5 mmol, 1.0 eq) in THF (10 mL) gave the title compound as a yellow oil in 91% yield (1.35 g). 1 H NMR(500MHz, CDCl3)δ7.95(t,J=7.7Hz,1H),7.68(d,J=7.9Hz,1H),7.37(d,J=7.6Hz,1H), 6.02(s,1H),4.39–4.34(m,2H),4.25–4.22(m,2H),2.44(s,3H),2.39(s,6H),2.06(s,6H). 13 C NMR (125 MHz, CDCl3) δ 161.35, 156.88, 138.36, 136.99, 132.58, 131.27, 125.40, 118.30, 104.41, 65.66, 18.00, 16.88, 16.48. HRMS for C 38 H 46 O2N4Na(2M + The calculated value of NH4Cl2 (Na) was 613.3513, and the measured value was 613.3475.

[0501]

[0502] 2-(1,3-Dioxolan-2-yl)-6-(2,4,6-tricyclohexylphenyl)pyridine. Prepared according to step 2 in general procedure B, reaction of (2-bromobenzene-1,3,5-triyl)tricyclohexane (2.42 g, 6 mmol, 1 eq), magnesium turnings (173 mg, 7.2 mmol, 1.44 eq), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine 6 (1.15 g, 5 mmol, 1.0 eq) in THF (10 mL) gave the title compound (805 mg) as a white solid in 34% yield. 1H NMR(500MHz, CDCl3)δ7.78(t,J=7.7Hz,1H),7.53(d,J=7.8Hz,1H),7.26–7.24(m,1H),7.01(s,2H),5.87(s,1H),4.22–4.14(m,2H),4.10–4.04 (m,2H),2.55–2.46(m,1H),2.07–1.99(m,2H),1.88–1.75(m,8H),1.67 –1.56(m,8H),1.43–1.31(m,8H),1.19–1.12(m,2H),1.03–0.94(m,4H). 13 C NMR (125 MHz, CDCl3) δ 159.67, 156.62, 147.89, 145.47, 136.50, 133.49, 125.44, 122.13, 118.35, 104.18, 65.62, 45.11, 41.41, 34.69, 34.63, 34.36, 27.16, 27.08, 26.92, 26.39, 26.31. HRMS for C 32 H 47 N2O2(M + +NH4) was 491.3632, and the measured value was 491.3654.

[0503]

[0504] 2-(2,6-Diisopropylphenyl)-6-(1,3-dioxolan-2-yl)pyridine. Prepared according to step 2 in general procedure B, reaction of 2-bromo-1,3-diisopropylbenzene (1.45 g, 6 mmol, 1 eq), magnesium turnings (173 mg, 7.2 mmol, 1.44 eq), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine 6 (1.15 g, 5 mmol, 1.0 eq) in THF (10 mL) gave the title compound (1.45 g) as a white solid in 93% yield. 1H NMR (500MHz, CDCl3) δ7.80(t,J=7.7Hz,1H),7.56(d,J=7.8Hz,1H),7.35(t,J=7.8Hz,1H),7.28–7.26(m,1H),7.21(d,J=7.7 Hz,2H),5.87(s,1H),4.24–4.17(m,2H),4.10–4.05(m,2H),2.51–2.42(m,2H),1.12(d,J=6.8Hz,6H),1.08(d,J=6.9Hz,6H). 13 CNMR (125 MHz, CDCl3) δ 159.39, 156.73, 146.63, 138.49, 136.67, 128.71, 125.41, 122.81, 118.63, 104.24, 65.71, 30.46, 24.27, 24.04. HRMS for C 20 H 29 N2O2(M + +NH4) was calculated to be 329.2224, and the measured value was 329.2257.

[0505]

[0506] 2-(6-(1,3-dioxolan-2-yl)pyridin-2-yl)-N,N-dimethylaniline. Prepared according to step 2 in general procedure B, the reaction of 2-bromo-N,N-dimethylaniline (1.2 g, 6 mmol, 1 equiv), magnesium turnings (173 mg, 7.2 mmol, 1.44 equiv), Pd-PEPPSI-IPr (102 mg, 0.15 mmol, 3 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine 6 (1.15 g, 5 mmol, 1.0 equiv) in THF (10 mL) gave the title compound as a yellow oil in 73% yield (987 mg). 1 H NMR (500MHz, CDCl3) δ7.92(d,J=7.3Hz,1H),7.72(t,J=7.8Hz,1H),7.61(d,J=7.1Hz,1H),7.45(d,J=7.5Hz,1 H),7.30(t,J=7.4Hz,1H),7.07–7.00(m,2H),5.91(s,1H),4.25–4.18(m,2H),4.12–4.07(m,2H),2.58(s,6H). 13C NMR (125 MHz, CDCl3) δ 158.93, 156.96, 151.51, 136.66, 132.39, 132.16, 129.37, 124.54, 121.89, 118.31, 117.58, 104.41, 65.72, 44.08. HRMS for C 32 H 40 N5O4(2M + +NH4) was calculated to be 561.3310 and the measured value was 561.3244.

[0507]

[0508] 2-Cyclohexyl-6-(1,3-dioxolan-2-yl)pyridine. Prepared according to step 2 in general procedure B, reaction of bromocyclohexane (978 mg, 6 mmol, 1 eq), magnesium turnings (173 mg, 7.2 mmol, 1.44 eq), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine (1.15 g, 5 mmol, 1.0 eq) in THF (10 mL) gave the title compound (1.05 g) as a white solid in 90% yield. 1 H NMR (500MHz, CDCl3) δ7.64(t,J=7.8Hz,1H),7.35(d,J=7.6Hz,1H),7.14(d,J=7.8Hz,1H),5.81(s,1H),4.19–4.14(m,2H),4.09– 4.04(m,2H),2.79–2.71(m,1H),2.00–1.93(m,2H),1.86–1.80(m,2H),1.76–1.71(m,1H),1.51–1.36(m,4H),1.31–1.24(m,1H). 13 C NMR (125 MHz, CDCl3) δ 166.42, 156.17, 137.14, 121.04, 117.72, 104.11, 65.65, 46.59, 33.11, 26.65, 26.20. HRMS for C 28 H 42 N3O4(2M + +NH4) was calculated to be 484.3170 and the measured value was 484.3091.

[0509]

[0510] 2-([1,1′:3′,1″-terphenyl]-5′-yl)-6-(1,3-dioxolan-2-yl)pyridine. Prepared according to step 2 in general procedure B, reaction of 5′-bromo-1,1′:3′,1″-terphenyl (1.86 g, 6 mmol, 1 equiv), magnesium turnings (173 mg, 7.2 mmol, 1.44 equiv), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine 6 (1.15 g, 5 mmol, 1.0 equiv) in THF (10 mL) gave the title compound as a colorless oil in 81% yield (1.54 g). 1 H NMR(500MHz, CDCl3)δ8.13(d,J=1.8Hz,2H),7.77–7.71(m,3H),7.63(d,J=7.0Hz,4H),7.55–7.49(m,1H),7.4 6–7.42(m,1H),7.39(t,J=7.7Hz,4H),7.32–7.28(m,1H),5.89(s,1H),4.17–4.10(m,2H),4.06–3.99(m,2H). 13 C NMR (125 MHz, CDCl3) δ 157.33, 157.03, 142.39, 141.22, 137.73, 128.92, 127.64, 127.51, 126.95, 125.20, 121.19, 119.23, 104.27, 65.78. HRMS for C 26 H 25 N2O2(M + +NH4) was calculated to be 397.1911, and the measured value was 397.1966.

[0511]

[0512] 2-(1,3-Dioxolan-2-yl)-6-(2,4,6-triisopropylphenyl)pyridine. Prepared according to step 2 in general procedure B, reaction of 2-bromo-1,3,5-triisopropylbenzene (1.36 g, 6 mmol, 1 eq), magnesium turnings (173 mg, 7.2 mmol, 1.44 eq), Ni(PCy3)Cl2 (34.5 mg, 0.05 mmol, 1 mol%) and 2-bromo-6-(1,3-dioxolan-2-yl)pyridine 6 (1.15 g, 5 mmol, 1.0 eq) in THF (10 mL) gave the title compound as a yellow oil in 94% yield (1.66 g). 1H NMR (500MHz, CDCl3) δ7.78(t,J=7.7Hz,1H),7.54(d,J=7.8Hz,1H),7.29(d,J=7.1Hz,1H),5.85(s,1H),4.26–4.17(m,2H),4.12 –4.03(m,2H),2.92(p,J=6.9Hz,1H),2.47(p,J=6.8Hz,2H),1.27(d,J=6.9Hz,6H),1.12(d,J=6.9Hz,6H),1.08(d,J=6.9Hz,6H). 13 C NMR (125MHz, CDCl3) δ159.67,156.68,148.97,146.39,136.58,136.21,12 5.56,120.86,118.47,104.33,65.69,34.59,30.49,24.32,24.25,24.07.

[0513] Imine intermediate synthesis

[0514]

[0515] 1-(6-(3,5-dimethylphenyl)pyridin-2-yl)-N-mesitylmethylaniline. 6-(3,5-dimethylphenyl)picolinaldehyde (422 mg, 2 mmol), 2,4,6-trimethylaniline (270 mg, 2 mmol) and formic acid (3 drops) were reacted in methanol (10 mL) at room temperature for 12 hours, then the solvent was concentrated to 3 mL, filtered and washed with methanol to give the title compound (575 mg, 85%) as a yellow solid. 1 H NMR (500MHz, CDCl3) δ8.43(s,1H),8.23(d,J=7.2Hz,1H),7.87(t,J=7.7Hz,1H),7.80(d,J= 6.8Hz,1H),7.66(s,2H),7.08(s,1H),6.90(s,2H),2.41(s,6H),2.30(s,3H),2.15(s,6H). 13 C NMR (125 MHz, CDCl3) δ 164.28, 157.83, 154.64, 148.16, 139.05, 138.53, 137.36, 133.40, 131.02, 128.89, 126.92, 125.01, 122.25, 119.22, 21.59, 20.92, 18.41. HRMS for C 23 H 25 N2(M +The calculated value of H (H) was 329.2012, and the found value was 329.2025.

[0516]

[0517] N-(2,6-diisopropylphenyl)-1-(6-(3,5-dimethylphenyl)pyridin-2-yl)methanimine. 6-(3,5-dimethylphenyl)picolinaldehyde (422 mg, 2 mmol), 2,6-diisopropylaniline (354 mg, 2 mmol) and formic acid (3 drops) were reacted in methanol (10 mL) at room temperature for 12 hours, then the solvent was concentrated to 3 mL, filtered and washed with methanol to give the title compound (570 mg, 77%) as a yellow solid. 1 H NMR (500MHz, CDCl3) δ8.41(s,1H),8.23(d,J=7.5Hz,1H),7.89(t,J=7.8Hz,1H),7.82(d,J=7.8Hz,1H),7.6 7(s,2H),7.20–7.16(m,2H),7.15–7.07(m,2H),3.01(p,J=6.8Hz,2H),2.42(s,6H),1.19(d,J=6.9Hz,12H). 13 C NMR (125 MHz, CDCl3) δ 163.77, 157.92, 154.46, 148.69, 139.03, 138.53, 137.41, 137.33, 131.05, 125.04, 124.47, 123.12, 122.33, 119.34, 28.11, 23.56, 21.60. HRMS for C 26 H 31 N2(M + The calculated value of H (H) was 371.2482, and the found value was 371.2500.

[0518]

[0519] 1-(6-(3,5-di-tert-butylphenyl)pyridin-2-yl)-N-mesitylmethoxybenzylmethanamine. 6-(3,5-di-tert-butylphenyl)picolinaldehyde (295 mg, 1 mmol), 2,4,6-trimethylaniline (135 mg, 1 mmol) and formic acid (3 drops) were reacted in methanol (5 mL) at room temperature for 12 hours, then the solvent was concentrated to 3 mL, filtered and washed with methanol to give the title compound (373 mg, 90%) as a yellow solid. 1H NMR (500MHz, CDCl3) δ8.44(s,1H),8.24(d,J=7.7Hz,1H),7.89(t,J=7.8Hz,1H),7.86(d,J=1.7H z, 2H), 7.81 (d, J = 7.7Hz, 1H), 7.53 (s, 1H), 6.91 (s, 2H), 2.30 (s, 3H), 2.16 (s, 6H), 1.40 (s, 12H). 13 C NMR (125 MHz, CDCl3) δ 164.64, 158.73, 154.55, 151.41, 148.31, 138.56, 137.32, 133.39, 128.88, 126.94, 123.60, 122.48, 121.63, 118.95, 35.18, 31.66, 20.91, 18.42. HRMS for C 29 H 37 N2(M + The calculated value of H (H) was 413.2951, and the found value was 413.2969.

[0520]

[0521] 1-(6-(3,5-di-tert-butylphenyl)pyridin-2-yl)-N-(2,6-diisopropylphenyl)methanimine. 6-(3,5-di-tert-butylphenyl)picolinaldehyde (295 mg, 1 mmol), 2,6-diisopropylaniline (177 mg, 1 mmol) and formic acid (3 drops) were reacted in methanol (5 mL) at room temperature for 12 hours, then the solvent was concentrated to 3 mL, filtered and washed with methanol to give the title compound (358 mg, 79%) as a yellow solid. 1 H NMR (500MHz, CDCl3) δ8.42(s,1H),8.23(d,J=7.2Hz,1H),7.90(t,J=7.7Hz,1H),7.87(d,J=1.8Hz,2H),7.83(d,J=7.9H z,1H),7.53(s,1H),7.21–7.16(m,2H),7.16–7.10(m,1H),3.03(p,J=6.8Hz,2H),1.40(s,19H),1.20(d,J=6.9Hz,12H). 13C NMR (125 MHz, CDCl3) δ 164.05, 158.78, 154.41, 151.42, 148.77, 138.53, 137.40, 137.39, 124.48, 123.64, 123.15, 122.54, 121.65, 119.09, 35.18, 31.65, 28.10, 23.56. HRMS for C 32 H 43 N2(M + The calculated value of H (H) was 455.3421, and the found value was 455.3443.

[0522] Additional intermediate synthesis

[0523]

[0524] 2-(2,6-diisopropoxyphenyl)-6-(1,3-dioxolan-2-yl)pyridine. A mixture of nBuLi (2.5M in hexane, 18 mL, 45 mmol, 1.5 equiv) and 2,6-diisopropoxybenzene (8.74 g, 45 mmol, 1.5 equiv) was stirred at 50 ° C for 14 h and continued for 36 h to obtain 2,6-diisopropoxyphenyllithium. In another flask, a few drops of 1,2-dibromoethane were added to Mg (1.08 g, 45 mmol, 1.5 equiv) in THF (50 mL). After the reaction was initiated, the remaining 1,2-dibromoethane (3.9 mL, 45 mmol) was added dropwise to maintain a steady exothermic reaction. After the addition, stirring was continued at 50 ° C for 1 h. The suspension of magnesium bromide was quickly poured into the aryl lithium. The mixture was stirred at 50 ° C for another 15 min. The mixture was cooled to room temperature. Then, 2-bromo-6-(1,3-dioxolane-2-yl)pyridine (6.9 g, 30 mmol, 1.0 equivalent) and Ni(PCy3)Cl2 (518 mg, 0.75 mmol, 2.5 mol%) were added to the mixture. The mixture was stirred at room temperature for 12 h, after which the mixture was poured onto an NH4Cl aqueous solution. The aqueous layer was extracted with ethyl acetate, and the combined organic extracts were washed with brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was loaded onto a short silica gel pad. After washing with hexane, the residue was eluted with hexane / ethyl acetate (4 / 1) until the product was completely recovered. The filtrate was concentrated in vacuo to obtain the desired product (10 g) as a colorless solid in a yield of 97%. 1H NMR (500MHz, CDCl3) δ7.63(t,J=7.7Hz,1H),7.37(d,J=7.1Hz,1H),7.21(d,J=7.7Hz,1H),7.11(t,J=8.3Hz,1H),6. 52(d,J=8.4Hz,2H),5.80(s,1H),4.34–4.25(m,2H),4.20–4.12(m,2H),4.09–3.99(m,2H),1.05(d,J=6.2Hz,12H). 13 C NMR (125 MHz, CDCl3) δ 156.86, 155.90, 154.45, 135.77, 129.13, 126.59, 122.32, 117.89, 107.89, 104.23, 71.30, 65.30, 22.02. HRMS for C 20 H 25 O4NK(2M + The calculated value of δ + K is 382.1415, and the measured value is 382.1450.

[0525]

[0526] 6-(2,6-diisopropoxyphenyl)picolinaldehyde. A mixture of 2-(2,6-diisopropoxyphenyl)-6-(1,3-dioxolan-2-yl)pyridine (9.96 g, 29 mmol) and 10% HCl solution (50 mL) was heated at 60 ° C in THF (100 mL) for 12 h. The mixture was quenched with an aqueous NaHCO solution. The aqueous layer was extracted with ethyl acetate, and the combined organic extracts were washed with brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the desired product (8.59 g) as a white solid in a 99% yield. 1 H NMR (500MHz, CDCl3) δ10.11 (s, 1H), 7.89–7.80 (m, 2H), 7.50 (dd, J = 7.5, 1.4Hz, 1H), 7. 24(t,J=4.2Hz,1H), 6.62(d,J=8.4Hz,2H), 4.48–4.37(m,2H), 1.13(d,J=6.1Hz,14H). 13 C NMR (125MHz, CDCl3) δ194.65,156.97,156.23,152.44,136.24,131.05,130.02,121.05,119.30,107.48,71.40,22.22.

[0527]

[0528] 2-(adamantan-1-yl)-6-(1,3-dioxolane-2-yl)pyridine. Preparation of ZnCl2 solution: A dry, argon-flushed 250 mL Schlenk flask equipped with a magnetic stir bar and a septum was charged with ZnCl2 (2.72 g, 20 mmol). The salt was heated to 140°C under high vacuum for 4 h. After cooling to 25°C, dry THF (20 mL) was added and stirring continued until the salt dissolved (4 h).

[0529] Preparation of 1-adamantyl zinc chloride solution: LiCl (466 mg, 11 mmol, 1.1 equivalents) was placed in a 25 mL Schlenk flask flushed with argon and dried by heating to approximately 500 ° C for 3 min with a heat gun in a full vacuum. After cooling to room temperature, Mg chips (480 mg, 20 mmol, 2.0 equivalents), 15 mL of THF and a 1M ZnCl solution in THF (11 mL, 11 mmol, 1.1 equivalents) were placed in a Schlenk flask. Magnesium was activated using 1,2-dibromoethane (5 mol%) and TMSCl (5 mol%). Pure 1-adamantyl bromide (2.15 g, 10 mmol, 1 equivalent) was then added. The solid turned black, the mixture began to boil and was cooled under reflux with an ice / water bath. The reaction mixture was stirred at 60 ° C until GC analysis of the hydrolyzed reaction aliquot showed that the starting material was completely consumed (typically 4 h). Titration of I2 showed a molarity of M = 0.2 mol / L (52% yield).

[0530] Negishi cross-coupling of adamantyl zinc reagent: Palladium acetate (22 mg, 0.1 mmol, 2 mol%), SPhos (82 mg, 0.2 mmol, 4 mol%) and 2-bromo-6-(1,3-dioxolane-2-yl)pyridine (1.15 g, 5 mmol, 1.0 equiv) were placed in a 25 mL Schlenk flask flushed with argon and dissolved in 10 mL of dry THF. The above 1-adamantyl zinc chloride solution in THF was then added at 65 ° C for 15 min. After further stirring at 65 ° C for 12 h, the mixture was poured onto an NH4Cl aqueous solution. The aqueous layer was extracted with ethyl acetate, and the combined organic extracts were washed with brine and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude residue was purified by silica gel flash chromatography (hexane / ethyl acetate 10 / 1 to 6 / 1) to obtain the desired product (756 mg) as a white solid with a yield of 53%. 1H NMR(500MHz, CDCl3)δ7.65(t,J=7.8Hz,1H),7.31(d,J=7.6Hz,1H),7.24(d,J=7.9Hz,1H), 5.84(s,1H),4.26–4.17(m,2H),4.12–4.04(m,2H),2.10(s,3H),2.01(s,6H),1.78(s,6H). 13 C NMR (125 MHz, CDCl3) δ 168.77, 156.00, 136.90, 119.27, 117.40, 104.55, 65.73, 41.99, 39.10, 36.96, 28.92. HRMS for C 36 H 50 N3O4(2M + +NH4) was 588.3796, and the measured value was 588.3716.

[0531] Synthesis of ligands

[0532]

[0533] 5-(2,6-Dimethylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (1). Prepared according to step 2 in general procedure A, reaction of 6-(2,6-dimethylphenyl)picolinaldehyde (211 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (0.5 mL, 2.0 mmol, 2 eq) in toluene (5 mL) gave the title compound (286 mg) as a white solid in 76% yield. 1 H NMR(500MHz, CDCl3)δ8.42(s,1H),8.04(d,J=9.5Hz,1H),7.87(s,1H),7.02(t,J=8.2Hz,1H), 6.80(t,J=7.6Hz,1H),6.73–6.56(m,3H),6.44(s,2H),1.73(s,3H),1.53(s,6H),1.44(s,6H). 13 C NMR (125 MHz, CDCl3) δ 140.93, 136.67, 133.32, 132.91, 131.55, 130.87, 130.67, 129.30, 128.81, 128.51, 125.60, 122.01, 120.02, 119.23, 117.80, 20.71, 18.97, 16.97. HRMS for C24 H 25 N2(M + The calculated value of 2-Cl) was 341.2012, and the found value was 341.2028.

[0534]

[0535]

[0146] 2-(2,6-Diisopropylphenyl)-5-(2,6-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (2). Prepared according to step 2 in general procedure A, reaction of 6-(2,6-dimethylphenyl)picolinaldehyde (211 mg, 1 mmol, 1 eq), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (0.5 mL, 2.0 mmol, 2 eq) in toluene (5 mL) gave the title compound (365 mg) as a white solid in 87% yield. 1 H NMR(500MHz, CDCl3)δ9.25(s,1H),8.93(d,J=9.5Hz,1H),7.94(s,1H),7.59–7.50(m,2H),7.39(t,J=7.6Hz,1H),7.29(d,J =8.1Hz,2H),7.25(d,J=7.6Hz,2H),7.15(d,J=7.0Hz,1H),2.09–2.02(m,8H),1.23(d,J=6.9Hz,6H),1.03(d,J=6.9Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 143.65, 135.97, 132.00, 131.19, 130.99, 130.52, 129.41, 128.06, 127.95, 125.44, 123.58, 121.17, 119.74, 119.08, 118.46, 27.70, 23.49, 22.93, 18.10. HRMS for C 27 H 31 N2(M + The calculated value of 3-Cl) is 383.2482, and the found value is 383.2503.

[0536]

[0537] 2-Mesityl-5-(2,4,6-triethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (3). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-triethylphenyl)pyridine (311 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (299 mg) as a white solid in 69% yield. 1 H NMR(500MHz, CDCl3)δ9.37(s,1H),8.96(d,J=9.3Hz,1H),7.86(s,1H),7.51–7.42(m,1H),7.11(s,2H),7.08(d,J=6.9Hz,1H),6.9 8(s,2H),2.68(q,J=7.6Hz,2H),2.37–2.28(m,5H),2.22–2.16(m,2H),1.95(s,6H),1.27(t,J=7.6Hz,3H),1.01(t,J=7.6Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 148.34, 143.45, 141.91, 133.99, 132.69, 132.66, 131.21, 129.90, 127.20, 125.60, 125.35, 121.45, 120.97, 120.88, 119.84, 28.93, 26.49, 21.23, 17.40, 16.16, 15.32. HRMS for C 28 H 33 N2(M + The calculated value of 3-Cl) was 397.2638, and the found value was 397.2658.

[0538]

[0539]

[0146] 2-(2,6-Diisopropylphenyl)-5-(2,4,6-triethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (4). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-triethylphenyl)pyridine (311 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (404 mg) as a white solid in 85% yield. 1 H NMR(500MHz, CDCl3)δ9.10(s,1H),8.82(d,J=9.3Hz,1H),7.88(s,1H),7.53–7.42(m,2H),7.24–7.19(m,2H),7.07(d,J=6.9,1H),7.04(s,2 H),2.61(q,J=7.6Hz,2H),2.30–2.21(m,2H),2.18–2.08(m,2H),2.02–1.92(m,2H),1.20(t,3H),1.15(d,J=6.7Hz,6H),0.97–0.91(m,12H). 13 C NMR (125 MHz, CDCl3) δ 147.93, 144.43, 142.84, 132.50, 131.92, 131.80, 130.08, 126.72, 126.08, 124.93, 124.31, 121.97, 120.89, 119.82, 119.05, 28.43, 25.93, 24.14, 23.75, 15.65, 14.77. HRMS for C 31 H 39 N2(M + The calculated value of 4-Cl) was 439.3108, and the found value was 439.3133.

[0540]

[0541]

[0146] 2-(2,6-Diisopropylphenyl)-5-(2,3,4,5,6-pentamethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (5). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,3,4,5,6-pentamethylphenyl)pyridine (595 mg, 2 mmol, 1 eq), 2,6-diisopropylaniline (354 mg, 2 mmol, 1.0 eq), paraformaldehyde (90 mg, 3 mmol, 1.5 eq) and 4M HCl in dioxane (2 mL, 8.0 mmol, 4 eq) in toluene (10 mL) gave the title compound (627 mg) as a white solid in 68% yield. 1 H NMR(500MHz, CDCl3)δ9.38(s,1H),9.10–8.95(m,1H),7.80(s,1H),7.55–7.43(m,2H),7.26–7.19(m,2H),7.03(d,J= 5.7Hz,1H),2.26(s,3H),2.20(s,6H),2.13–2.02(m,2H),1.91(s,7H),1.22(d,J=5.6Hz,6H),0.99(d,J=5.7Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 144.95, 138.99, 134.68, 134.62, 132.43, 132.23, 132.10, 130.76, 127.33, 126.02, 124.73, 121.88, 121.40, 120.78, 120.73, 28.89, 24.81, 24.04, 17.34, 17.19, 16.71. HRMS for C 30 H 37 N2(M + The calculated value of 4-Cl) was 425.2951 and the found value was 425.2966.

[0542]

[0543]

[00156] 2-Mesityl-5-(2,4,6-tricyclohexylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (6). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-tricyclohexylphenyl)pyridine (474 ​​mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (435 mg) as a white solid in 73% yield. 1 H NMR (500MHz, CDCl3) δ9.37 (d, J = 2.0Hz, 1H), 9.03 (d, J = 9.4Hz, 1H), 7.88 (d, J = 1.8Hz, 1H) ,7.45(dd,J=9.4,6.8Hz,1H),7.10(s,2H),6.98(d,J=7.1Hz,1H),6.96(s,2H),2.56–2.4 6(m,1H),2.30(s,3H),1.94–1.82(m,10H),1.79–1.75(m,2H),1.73–1.67(m,4H),1.64–1 .57(m,4H),1.51–1.22(m,12H),1.18–1.09(m,2H),1.06–0.97(m,2H),0.89–0.80(m,2H). 13 C NMR (125 MHz, CDCl3) δ 151.95, 146.84, 141.90, 133.97, 132.97, 132.63, 131.13, 129.78, 125.31, 124.66, 123.80, 121.37, 121.08, 120.68, 119.61, 44.99, 42.47, 35.16, 35.00, 34.36, 26.83, 26.57, 26.07, 25.63, 21.18, 16.88. HRMS for C 40 H 51 N2(M + The calculated value of –Cl) is 559.4047, and the measured value is 559.4071.

[0544]

[0545]

[0146] 2-(2,6-Diisopropylphenyl)-5-(2,4,6-tricyclohexylterphenyl)imidazo[1,5-a]pyridin-2-ium chloride (7). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-tricyclohexylphenyl)pyridine (474 ​​mg, 1 mmol, 1 eq), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (465 mg) as a white solid in 73% yield. 1 H NMR(500MHz, CDCl3)δ9.50(s,1H),9.17(d,J=9.3Hz,1H),7.93(s,1H),7.54–7.49(m,2H),7 .28(d,J=7.8Hz,2H),7.12(s,2H),7.02(d,J=6.7Hz,1H),2.55–2.49(m,1H),2.03–1.99(m,2 H),1.89–1.84(m,4H),1.77–1.64(m,12H),1.57–1.50(m,2H),1.43–1.32(m,8H),1.22(d,J= 6.7Hz, 6H), 1.18–1.13 (m, 2H), 1.11–1.06 (m, 2H), 1.03 (d, J = 6.9Hz, 6H), 0.93–0.88 (m, 2H). 13 C NMR (125 MHz, CDCl3) δ 152.01, 146.95, 145.04, 132.82, 132.59, 132.26, 130.67, 125.61, 124.73, 123.83, 121.75, 121.50, 121.14, 120.93, 45.02, 42.57, 35.59, 34.61, 34.39, 28.98, 26.88, 26.72, 26.59, 26.12, 25.70, 24.89, 23.97. HRMS for C 43 H 57 N2(M + The calculated value of 1-Cl) was 601.4516, and the found value was 601.4543.

[0546]

[0547]

[0146] 5-(2,6-Diisopropylphenyl)-2-(2,6-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (8). Prepared according to step 3 in general procedure B, reaction of 2-(2,6-diisopropylphenyl)-6-(1,3-dioxolan-2-yl)pyridine (311 mg, 1 mmol, 1 equiv), 2,6-dimethylaniline (121 mg, 1 mmol, 1.0 equiv), paraformaldehyde (45 mg, 1.5 mmol, 1.5 equiv) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 equiv) in toluene (5 mL) gave the title compound (314 mg) as a white solid in 75% yield. 1 H NMR(500MHz, CDCl3)δ9.43(s,1H),9.01(d,J=9.6Hz,1H),7.91(s,1H),7.56(t,J=7.9Hz,1H),7.49(dd,J=9.3,6.9Hz,1H),7.39–7.3 2(m,3H),7.19(d,J=7.8Hz,2H),7.07(d,J=6.9Hz,1H),2.38–2.26(m,2H),1.98(s,6H),1.16(d,J=6.7Hz,6H),1.04(d,J=6.9Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 148.23, 134.42, 133.58, 132.78, 132.52, 132.42, 131.64, 129.32, 126.85, 125.44, 124.70, 121.60, 120.95, 120.73, 119.80, 31.35, 24.98, 24.09, 17.31. HRMS for C 27 H 31 N2(M + The calculated value of 3-Cl) is 383.2482, and the found value is 383.2503.

[0548]

[0549]

[0146] 5-(2,6-Diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (9). Prepared according to step 3 in general procedure B, reaction of 2-(2,6-diisopropylphenyl)-6-(1,3-dioxolan-2-yl)pyridine (311 mg, 1 mmol, 1 equiv), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 equiv), paraformaldehyde (45 mg, 1.5 mmol, 1.5 equiv) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 equiv) in toluene (5 mL) gave the title compound (385 mg) as a white solid in 89% yield. 1 H NMR(500MHz, CDCl3)δ9.01(s,1H),8.76(d,J=9.4Hz,1H),7.90(s,1H),7.61–7.46(m,2H),7.35(d,J=7.8Hz,2H), 7.08(d,J=6.7Hz,1H),6.98(s,2H),2.39–2.26(m,5H),1.93(s,6H),1.15(d,J=6.6Hz,6H),1.03(d,J=6.7Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 148.24, 142.04, 134.01, 132.71, 132.53, 132.46, 131.09, 129.92, 126.81, 125.71, 124.72, 121.24, 120.96, 120.89, 119.30, 31.36, 25.02, 24.11, 21.25, 17.25. HRMS for C 28 H 33 N2(M + The calculated value of 3-Cl) is 397.2683, and the found value is 397.2660.

[0550]

[0551]

[0146] 2,5-Bis(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (10). Prepared according to step 3 in general procedure B, reaction of 2-(2,6-diisopropylphenyl)-6-(1,3-dioxolan-2-yl)pyridine (311 mg, 1 mmol, 1 equiv), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 equiv), paraformaldehyde (45 mg, 1.5 mmol, 1.5 equiv) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 equiv) in toluene (5 mL) gave the title compound (385 mg) as a white solid in 81% yield. 1H NMR(500MHz, CDCl3)δ9.34(s,1H),9.12–8.95(m,1H),7.89(s,1H),7.59–7.49(m,3H),7.35(d,J=7.8Hz,2H),7.28( d,J=7.8Hz,2H),7.13–7.07(m,1H),2.39–2.24(m,2H),2.09–1.96(m,2H),1.26–1.14(m,12H),1.08–0.99(m,12H). 13 C NMR (125 MHz, CDCl3) δ 148.31, 145.08, 132.61, 132.46, 132.36, 130.50, 126.87, 125.86, 124.76, 124.65, 121.85, 121.79, 121.58, 121.53, 121.32, 31.49, 28.98, 25.18, 24.83, 24.43, 23.96. HRMS for C 31 H 39 N2(M + The calculated value of 4-Cl) was 439.3108, and the found value was 439.3134.

[0552]

[0553]

[0146] 2-Cyclohexyl-5-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (11). Prepared according to step 3 in general procedure B, reaction of 2-(2,6-diisopropylphenyl)-6-(1,3-dioxolan-2-yl)pyridine (311 mg, 1 mmol, 1 equiv), cyclohexylamine (177 mg, 1 mmol, 1.0 equiv), paraformaldehyde (45 mg, 1.5 mmol, 1.5 equiv) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 equiv) in toluene (5 mL) gave the title compound (242 mg) as a white solid in 61% yield. 1H NMR (500MHz, CDCl3) δ9.37 (s, 1H), 8.26 (s, 1H), 8.20 (d, J = 9.3Hz, 1H), 7.59 (t, J=7.9Hz,1H),7.37(d,J=7.9Hz,2H),7.35–7.32(m,1H),6.91(d,J=6.7Hz,1H),5 .02–4.94(m,1H),2.27–2.20(m,4H),1.90–1.84(m,2H),1.74–1.66(m,3H),1.6 0–1.50(m,2H),1.27–1.21(m,1H),1.11(d,J=6.9Hz,6H),1.05(d,J=6.9Hz,6H). 13 CNMR (125 MHz, CDCl3) δ 148.16, 133.17, 132.21, 131.12, 126.84, 124.69, 124.60, 119.96, 119.54, 119.27, 116.37, 61.41, 34.23, 31.20, 25.07, 24.93, 24.59, 24.07. HRMS for C 25 H 33 N2(M + The calculated value of 3-Cl) was 361.2638, and the found value was 361.2654.

[0554]

[0555]

[0146] 2-(2,6-Diisopropylphenyl)-5-(2,6-dimethoxyphenyl)imidazo[1,5-a]pyridin-2-ium chloride (12). Prepared according to step 2 in general procedure A, reaction of 6-(2,6-dimethoxyphenyl)picolinaldehyde (487 mg, 2 mmol, 1 eq), 2,6-diisopropylaniline (354 mg, 2 mmol, 1.0 eq), paraformaldehyde (90 mg, 3 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 2 eq) in toluene (10 mL) gave the title compound (749 mg) as a white solid in 83% yield. 1H NMR (500MHz, CDCl3) δ8.87(s,1H),8.72–8.60(m,1H),8.15(s,1H),7.58–7.42(m,3H),7.30(d,J=7.9Hz,2H),7.14(d ,J=6.9Hz,1H),6.73(d,J=8.4Hz,2H),3.75(s,6H),2.22–2.11(m,2H),1.21(d,J=6.7Hz,7H),1.09(d,J=6.7Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 158.42, 145.09, 133.86, 133.78, 132.16, 130.79, 128.52, 125.90, 124.66, 122.94, 122.10, 120.13, 118.61, 107.30, 104.65, 56.34, 56.32, 28.67, 24.50. HRMS for C 27 H 31 N2O2(M + The calculated value of 4-Cl) was 415.2380, and the found value was 415.2397.

[0556]

[0557]

[0146] 2-(2,6-Diisopropylphenyl)-5-(2,4,6-trimethoxyphenyl)imidazo[1,5-a]pyridin-2-ium chloride (13). Prepared according to step 2 in general procedure A, reaction of 6-(2,4,6-trimethoxyphenyl)picolinaldehyde (547 mg, 2 mmol, 1 eq), 2,6-diisopropylaniline (354 mg, 2 mmol, 1.0 eq), paraformaldehyde (90 mg, 3 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 2 eq) in toluene (10 mL) gave the title compound (519 mg) as a white solid in 54% yield. 1 H NMR(500MHz,MeOD)δ9.50(s,1H),8.33(d,J=1.8Hz,1H),7.90(d,J=9.3Hz,1H),7.63(t,J=7.9Hz,1H),7.50(dd,J=9.3,7.0Hz,1H),7.45(d,J =7.8Hz,2H),7.18(d,J=7.0Hz,1H),6.41(s,2H),3.90(s,3H),3.78(s,7H),2.22–2.12(m,2H),1.21(d,J=6.8Hz,6H),1.18(d,J=6.9Hz,6H). 13C NMR (125 MHz, MeOD) δ 165.97, 160.86, 146.44, 133.04, 132.71, 132.65, 131.59, 128.72, 127.42, 125.63, 122.70, 117.78, 117.57, 101.44, 92.32, 56.71, 56.20, 29.90, 24.64, 24.19. HRMS for C 28 H 33 N2O3(M + The calculated value of 4-Cl) was 445.2486, and the found value was 445.2503.

[0558]

[0559] 5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (14). To a mixture of 6-(2,6-diisopropoxyphenyl)picolinaldehyde (6 g, 20 mmol, 1 eq), 2,6-diisopropylaniline (3.54 g, 20 mmol, 1 eq), paraformaldehyde (900 mg, 30 mmol, 1.5 eq) in toluene (100 mL, 0.2 M) was added 4 M HCl in dioxane (10 ml, 40 mmol, 2 eq). The mixture was then heated at 100 ° C for 3 h. The solvent was removed under reduced pressure. The residue was triturated with ethyl acetate to give the desired product (9.02 g) as a white solid in 89% yield. 1 H NMR (500MHz, DMSO) δ9.89 (s, 1H), 8.79–8.71 (m, 1H), 8.02 (d, J = 8.9Hz, 1H), 7.64 ( t,J=7.8Hz,1H),7.53(dd,J=9.3,6.9Hz,1H),7.48(t,J=8.5Hz,1H),7.45(d,J=7. 8Hz,2H),7.19(d,J=6.9Hz,1H),6.86(d,J=8.5Hz,2H),4.58–4.49(m,2H),2.04–1 .93(m,2H),1.12(d,J=6.9Hz,6H),1.08(d,J=6.3Hz,12H),0.97(d,J=6.0Hz,6H). 13C NMR (125 MHz, DMSO) δ 156.91, 144.49, 132.83, 131.50, 131.11, 130.25, 130.03, 127.40, 126.19, 124.22, 120.60, 117.28, 116.82, 110.74, 107.70, 71.08, 28.26, 24.34, 23.32, 21.76, 21.63. HRMS for C 31 H 39 N2O2(M + The calculated value of 4-Cl) was 471.3006, and the found value was 471.3024.

[0560]

[0561]

[0146] 5-(2-(Dimethylamino)phenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (15). Prepared according to step 3 in general procedure B, reaction of 2-(6-(1,3-dioxolan-2-yl)pyridin-2-yl)-N,N-dimethylaniline (270 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (266 mg) as a white solid in 68% yield. 1 H NMR(500MHz, CDCl3)δ9.02(s,1H),8.76(d,J=9.3Hz,1H),8.16(s,1H),7.56–7.50(m,2H),7.48–7.44(m,1H) ,7.27(s,1H),7.19(t,J=8.4Hz,2H),7.04–6.99(m,2H),2.53(s,6H),2.35(s,3H),2.06(s,3H),1.97(s,3H). 13 C NMR (125 MHz, CDCl3) δ 150.77, 141.82, 136.17, 134.39, 133.85, 133.29, 132.52, 131.52, 131.32, 130.05, 129.77, 125.41, 124.20, 122.89, 120.59, 119.46, 118.63, 117.94, 43.32, 21.28, 17.70, 16.99. HRMS for C 24 H 26 N3(M +The calculated value of 3-Cl) is 356.2121, and the found value is 356.2139.

[0562]

[0563]

[0266] 2-(2,6-Diisopropylphenyl)-5-(2-(dimethylamino)phenyl)imidazo[1,5-a]pyridin-2-ium chloride (16). Prepared according to step 3 in general procedure B, reaction of 2-(6-(1,3-dioxolan-2-yl)pyridin-2-yl)-N,N-dimethylaniline (270 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (304 mg) as a white solid in 70% yield. 1 H NMR (500MHz, CDCl3) δ9.19 (s, 1H), 8.95 (d, J = 9.9Hz, 1H), 8.06 (s, 1H), 7.58–7. 49(m,3H),7.48(d,J=6.0Hz,1H),7.33(d,J=7.8Hz,1H),7.30(d,J=7.2Hz,2H),7 .22–7.13(m,2H),2.54(s,6H),2.39–2.30(m,1H),1.97–1.93(m,1H),1.25(d,J= 6.7Hz, 3H), 1.20 (d, J = 6.7Hz, 3H), 1.17 (d, J = 6.9Hz, 3H), 0.97 (d, J = 6.7Hz, 3H). 13 C NMR (125 MHz, CDCl3) δ 149.47, 143.91, 143.49, 135.06, 132.57, 131.71, 131.26, 130.27, 129.56, 125.67, 124.44, 123.80, 123.43, 121.92, 121.06, 120.11, 119.59, 119.44, 117.70, 43.14, 27.78, 27.71, 24.42, 24.04, 23.57, 23.36. HRMS for C 27 H 32 N3(M + The calculated value of 3-Cl) was 398.2591, and the found value was 398.2608.

[0564]

[0565] 2-(2,6-bis(2-benzhydryl-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride (17). An oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with 6-mesityl pyridinecarboxaldehyde (450 mg, 2.0 mmol, 1.0 equiv), 2,6-bis(2-benzhydryl-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride. 6-mesityl pyridinecarboxaldehyde (450 mg, 2.0 mmol, 1.0 equiv), 2,6-bis(2-benzhydryl-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride (17) was added to a 100 mL round-bottom flask dried in an oven and equipped with a stir bar. Paraformaldehyde (90 mg, 3.0 mmol, 1.5 equiv) and toluene (10 mL) were added. The reaction mixture was stirred at 100 ° C and 4 M HCl in dioxane (1 mL, 4.0 mmol, 2 equiv) was added. The resulting reaction mixture was stirred at 100 ° C for 12 h. The crude product was purified by column chromatography (CHCl / MeOH 50 / 1 to 15 / 1). The title product was obtained as a white solid in 87% yield by trituration from diethyl ether / ethyl acetate (1.21 g). 1 H NMR(500MHz, CDCl3)δ9.19(s,1H),8.65(d,J=9.3Hz,1H),7.40(dd,J=9.3,6.8Hz,1H),7.29–7.25(m,4H),7.18–7.09(m,6H),7 .06–6.99(m,5H),6.87(d,J=6.7Hz,1H),6.84(s,2H),6.81–6.72(m,6H),5.08(s,2H),2.35(s,3H),2.21(s,3H),1.57(s,6H). 13 C NMR (125 MHz, CDCl3) δ 142.15, 141.89, 141.75, 141.00, 140.18, 136.64, 132.96, 131.48, 130.87, 130.74, 129.80, 129.31, 128.81, 128.75, 128.53, 127.24, 127.19, 125.91, 125.43, 122.89, 120.50, 120.44, 119.95, 51.31, 21.93, 21.33, 19.54. HRMS for C 49 H 43 N2(M + The calculated value of 1-Cl) was 659.3421, and the found value was 659.3466.

[0566]

[0567] 2-(2,6-bis(2-benzhydryl)-4-methoxyphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride (18). An oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with 6-mesityl pyridinecarboxaldehyde (450 mg, 2.0 mmol, 1.0 equiv), 2,6-bis(2-benzhydryl)-4-methoxyaniline (911 mg, 2 mmol, 1.0 equiv), paraformaldehyde (90 mg, 3.0 mmol, 1.5 equiv) and toluene (10 mL). The reaction mixture was stirred at 100 ° C and 4M HCl in dioxane (1 mL, 4.0 mmol, 2 equiv) was added. The resulting reaction mixture was stirred at 100 ° C for 12 h. The crude product was purified by column chromatography (CHCl / MeOH 50 / 1 to 15 / 1). The title product was obtained as a white solid in 89% yield by trituration from diethyl ether / ethyl acetate (1.26 g). 1 H NMR(500MHz, CDCl3)δ9.28(s,1H),8.68(d,J=9.4Hz,1H),7.45(dd,J=9.4,6.8Hz,1H),7.35–7.31(m,4H),7.30–7.26(m,2H) ,7.24–7.17(m,6H),7.13–7.06(m,5H),6.94–6.83(m,7H),6.54(s,2H),5.15(s,2H),3.59(s,3H),2.41(s,3H),1.62(s,6H). 13 C NMR (125 MHz, CDCl3) δ 161.10, 142.23, 141.95, 141.57, 141.00, 136.62, 132.99, 131.40, 129.72, 129.33, 128.85, 128.78, 128.48, 127.37, 127.27, 125.94, 125.91, 125.32, 123.21, 120.47, 120.34, 115.72, 55.41, 51.56, 21.34, 19.54. HRMS for C 49 H 43 N2O(M + -Cl) was calculated to be 675.3370 and found to be 675.3413.

[0568]

[0569] 2-(2,6-Bis(2-phenylmethyl)-4-methoxyphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (19). An oven-dried 100 mL round-bottom flask equipped with a stir bar was charged with 6-(2,4,6-triisopropylphenyl)picolinaldehyde (450 mg, 2.0 mmol, 1.0 eq), 2,6-bis(2-phenylmethyl)-4-methylaniline (879 mg, 2 mmol, 1.0 eq), paraformaldehyde (90 mg, 3.0 mmol, 1.5 eq) and toluene (10 mL). The reaction mixture was stirred at 100° C. and 4 M HCl in dioxane (1 mL, 4.0 mmol, 2 eq) was added. The resulting reaction mixture was stirred at 100° C. for 12 h. The crude product was purified by column chromatography (CH2Cl2 / MeOH 50 / 1 to 15 / 1).The title product (1.11 g) was obtained in 71% yield as a white solid by trituration from diethyl ether / ethyl acetate. 1 H NMR (500MHz, CDCl3) δ8.71(s,1H),7.76(s,2H),7.26–7.17(m,14H),7.14–7.09(m,1H),6.90(d,J=6.7Hz,4H),6.79–6.71(m,6H),6.40(s, 1H), 4.89 (s, 2H), 3.05–2.97 (m, 1H), 2.35–2.27 (m, 2H), 2.21 (s, 3H), 1.34 (d, J = 7.0Hz, 6H), 1.15 (d, J = 6.7Hz, 6H), 1.08 (d, J = 6.9Hz, 6H). 13 C NMR (125 MHz, CDCl3) δ 153.24, 147.98, 142.50, 142.05, 141.76, 140.85, 140.81, 133.14, 130.76, 130.50, 129.29, 129.23, 128.85, 128.70, 127.90, 127.36, 127.32, 124.18, 122.74, 122.52, 121.95, 119.02, 118.73, 52.17, 34.63, 31.64, 29.84, 25.18, 24.55, 24.01, 22.01. HRMS for C 55 H 55 N2(M + The calculated value of 1-Cl) was 743.4360 and the found value was 743.4390.

[0570]

[0571]

[0146] 2-(2,6-Bis(2-phenylmethyl)-4-fluorophenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (20). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-triisopropylphenyl)pyridine (354 mg, 1 mmol, 1 eq), 2,6-bis(2-phenylmethyl)-4-fluoroaniline (444 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (682 mg) as a white solid in 87% yield. 1 H NMR(500MHz, CDCl3)δ9.56(s,1H),7.65–7.47(m,2H),7.26–7.11(m,14H),7.04–7.01(m,1H),7.01–6.90(m,4H),6.75(s,4H),6.6 9–6.58(m,2H),6.39–6.19(m,1H),5.01(s,2H),3.06–2.96(m,1H),2.36–2.25(m,2H),1.34(d,J=4.8Hz,6H),1.20–1.08(m,12H). 13 C NMR (125MHz, CDCl3) δ163.48(d,J=253.9Hz),153.15,147.80,144.45(d,J=5.4Hz),141.21,140.18(d,J=8.7Hz),133.77,129.33,129.27,1 28.98,128.64,127.94,127.55,124.15,122.76,121.52,118.81,118 .20,117.44(d,J=24.5Hz),52.24,34.55,31.69,25.13,24.56,24.00. 19 F NMR (471 MHz, CDCl3) δ -105.11. HRMS for C 54 H 52 FN2(M + The calculated value of 1-Cl) was 747.4109, and the found value was 747.4136.

[0572]

[0573]

[0146] 5-Cyclohexyl-2-mesitylphenylimidazo[1,5-a]pyridin-2-ium chloride (21). Prepared according to step 3 in general procedure B, reaction of 2-cyclohexyl-6-(1,3-dioxolan-2-yl)pyridine (233 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (248 mg) as a white solid in 70% yield. 1 H NMR (500MHz, CDCl3) δ11.65(s,1H),7.63(d,J=8.9Hz,2H),7.27–7.25(m,1H),7.02(s,2H),6.90(d,J=7.0Hz,1H),4.07–3.99(m ,1H),2.33(s,3H),2.21–2.16(m,2H),2.09(s,6H),2.01–1.92(m,2H),1.85–1.77(m,3H),1.46–1.38(m,2H),1.32–1.19(m,1H). 13 C NMR (125 MHz, CDCl3) δ 144.36, 141.34, 134.16, 131.54, 131.10, 129.95, 128.32, 126.21, 115.36, 113.54, 113.12, 38.29, 31.45, 26.33, 25.41, 21.28, 17.86. HRMS for C 22 H 27 N2(M + The calculated value of 3-Cl) was 319.2169, and the found value was 319.2184.

[0574]

[0575]

[0146] 5-Cyclohexyl-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (22). Prepared according to step 3 in general procedure B, reaction of 2-cyclohexyl-6-(1,3-dioxolan-2-yl)pyridine (233 mg, 1 mmol, 1 eq), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (310 mg) as a white solid in 78% yield. 1H NMR (500MHz, CDCl3) δ11.94(s,0.2H),11.58(s,0.8H),7.80–7.67(m,2H),7.54(t,J=7.9Hz,1H),7.38–7.27(m,3H),6.95(d,J=7.0Hz,1H),4 .05(t,J=11.5Hz,1H),2.19–2.14(m,3H),2.01–1.92(m,2H),1.86–1.7 6(m,3H),1.48–1.38(m,2H),1.33–1.24(m,7H),1.15(d,J=6.9Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 145.09, 144.10, 131.99, 131.05, 130.99, 128.58, 126.45, 124.66, 115.76, 115.04, 113.43, 38.28, 31.34, 28.97, 26.33, 25.39, 24.66, 24.48. HRMS for C 25 H 33 N2(M + The calculated value of 3-Cl) was 361.2638, and the found value was 361.2656.

[0576]

[0577]

[0146] 5-(Adamantan-1-yl)-2-mesitylphenylimidazo[1,5-a]pyridin-2-ium chloride (23). Prepared according to Step 3 in General Procedure B, reaction of 2-(adamantan-1-yl)-6-(1,3-dioxolan-2-yl)pyridine (285 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (334 mg) as a white solid in 82% yield. 1 H NMR(500MHz, CDCl3)δ9.40–9.26(m,1H),8.15(s,1H),7.80(d,J=9.2Hz,1H),6.86–6.74(m,1H),6.60–6.4 9(m,3H),1.84(s,3H),1.71(s,3H),1.67(s,6H),1.54(s,6H),1.41(d,J=11.9Hz,3H),1.35–1.27(m,3H). 13C NMR (125 MHz, CDCl3) δ 143.59, 140.62, 133.46, 132.35, 130.84, 129.12, 124.95, 124.62, 117.72, 115.43, 115.34, 37.64, 37.43, 35.56, 27.33, 20.60, 17.10, 17.05. HRMS for C 26 H 31 N2(M + The calculated value of 3-Cl) was 371.2482, and the found value was 371.2501.

[0578]

[0579]

[0146] 5-(Adamantan-1-yl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (24). Prepared according to Step 3 in General Procedure B, reaction of 2-(adamantan-1-yl)-6-(1,3-dioxolan-2-yl)pyridine (285 mg, 1 mmol, 1 eq), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (386 mg) as a white solid in 86% yield. 1 H NMR(500MHz, CDCl3)δ9.29(s,1H),8.73(s,1H),8.33(d,J=9.2Hz,1H),7.39(t,J=7.9Hz,1H),7.20–7.13(m,3H),6.96(d, J=7.2Hz,1H),2.03–1.99(m,3H),1.97–1.89(m,8H),1.64(d,J=12.4Hz,7H),1.00(d,J=6.9Hz,6H),0.97(d,J=6.9Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 144.43, 142.95, 132.73, 131.75, 130.33, 125.48, 124.27, 123.92, 118.89, 117.48, 116.22, 37.88, 37.59, 35.81, 28.31, 27.45, 24.33, 23.64. HRMS for C 29 H 37 N2(M + The calculated value of 4-Cl) was 413.2951, and the found value was 413.2971.

[0580]

[0581] 5-(3,5-Dimethylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (25). The corresponding imine (225 mg, 0.68 mmol), paraformaldehyde (21 mg, 0.68 mmol), trimethylsilyl chloride (146 mg, 1.36 mmol) were reacted in toluene (4 mL) at 70 ° C. for 15 h, and then the solvent was removed and the residue was triturated with ethyl acetate and diethyl ether to give the title compound (238 mg, 93%) as a white solid. 1 H NMR (500MHz, CDCl3) δ9.05 (s, 1H), 8.84 (s, 1H), 8.64 (d, J = 9.2Hz, 1H), 7.49–7.42 (m, 1H), 7. 34–7.28(m,3H),7.14(d,J=6.9Hz,1H),7.07(s,2H),2.45(s,6H),2.40(s,3H),2.11(s,6H). 13 C NMR (125 MHz, CDCl3) δ 141.79, 140.27, 135.49, 134.13, 133.21, 132.61, 131.31, 130.87, 129.99, 126.05, 125.78, 122.23, 120.16, 119.20, 118.47, 21.52, 21.26, 17.79. HRMS for C 24 H 25 N2(M + The calculated value of -Cl) is 341.2012, and the found value is 341.2026.

[0582]

[0583] 2-(2,6-diisopropylphenyl)-5-(3,5-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (26). The corresponding imine (370 mg, 1 mmol), paraformaldehyde (30 mg, 1 mmol), trimethylsilyl chloride (217 mg, 2 mmol) were reacted in toluene (4 mL) at 70° C. for 15 h, then the solvent was removed and the residue was triturated with ethyl acetate and diethyl ether to give the title compound (369 mg, 88%) as a white solid. 1H NMR (500MHz, CDCl3) δ9.34(s,1H),8.92(d,J=9.3Hz,1H),8.58(s,1H),7.56(t,J=7.9Hz,1H),7.50–7.43(m,1H),7.33(d,J=7. 8Hz, 2H), 7.20 (s, 3H), 7.14 (d, J = 6.9Hz, 1H), 2.38 (s, 6H), 2.17 (p, J = 6.8Hz, 2H), 1.26 (d, J = 6.9Hz, 6H), 1.12 (d, J = 6.8Hz, 6H). 13 C NMR (125 MHz, CDCl3) δ 145.11, 140.35, 134.82, 133.20, 132.76, 132.29, 130.94, 130.73, 126.01, 125.80, 124.82, 122.04, 121.15, 120.08, 119.58, 28.86, 24.86, 24.26, 21.46. HRMS for C 27 H 31 N2(M + The calculated value of 3-Cl) is 383.2482, and the found value is 383.2501.

[0584]

[0585] 5-(3,5-di-tert-butylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (27). The corresponding imine (350 mg, 0.85 mmol), paraformaldehyde (26 mg, 0.85 mmol), trimethylsilyl chloride (185 mg, 1.7 mmol) were reacted in toluene (4 mL) at 70° C. for 15 h, and then the solvent was removed and the residue was triturated with ethyl acetate and diethyl ether to give the title compound (372 mg, 95%) as a white solid. 1 H NMR (500MHz, CDCl3) δ9.26 (s, 1H), 8.73 (d, J = 9.3Hz, 1H), 8.49 (s, 1H), 7.63 (s, 1H), 7.45–7. 37(m,3H),7.12(d,J=5.0Hz,1H),7.01(s,2H),2.34(s,3H),2.05(s,6H),1.35–1.31(m,18H). 13C NMR (125 MHz, CDCl3) δ 153.35, 141.82, 135.68, 133.95, 132.86, 131.26, 130.55, 130.03, 125.73, 125.64, 122.37, 121.39, 120.80, 119.37, 119.32, 35.30, 31.45, 21.24, 17.67. HRMS for C 30 H 37 N2(M + The calculated value of 4-Cl) was 425.2951, and the found value was 425.2970.

[0586]

[0587] 5-(3,5-di-tert-butylphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (28). The corresponding imine (330 mg, 0.72 mmol), paraformaldehyde (22 mg, 0.72 mmol), trimethylsilyl chloride (156 mg, 1.44 mmol) were reacted in toluene (4 mL) at 70° C. for 15 h, then the solvent was removed and the residue was triturated with ethyl acetate and diethyl ether to give the title compound (315 mg, 87%) as a white solid. 1 H NMR(500MHz, CDCl3)δ8.89(s,1H),8.65(d,J=9.4Hz,1H),8.39(s,1H),7.64(s,1H),7.59–7.51(m,2H),7.43(d,J=1.8Hz,2H),7 .32(d,J=7.9Hz,2H),7.17(d,J=6.9Hz,1H),2.23(p,J=6.8Hz,2H),1.34(s,18H),1.25(d,J=6.8Hz,6H),1.11(d,J=6.8Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 153.38, 145.29, 135.72, 132.69, 132.32, 130.71, 130.57, 126.46, 125.74, 124.78, 122.52, 121.99, 120.47, 119.91, 119.47, 35.33, 31.46, 28.83, 24.77, 24.46. HRMS for C 33 H 43 N2(M + The calculated value of 4-Cl) was 467.3421, and the found value was 467.3445.

[0588]

[0589]

[00155] 5-([1,1':3',1"-terphenyl]-5'-yl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (29). Prepared according to step 3 in general procedure B, reaction of 2-([1,1':3',1"-terphenyl]-5'-yl)-6-(1,3-dioxolan-2-yl)pyridine (379 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 eq) in toluene (5 mL) gave the title compound (436 mg) as a white solid in 87% yield. 1 H NMR (500MHz, CDCl3) δ9.01(s,1H),8.86(s,1H),8.51(d,J=9.3Hz,1H),7.97(s,1H),7.88(s,2H),7.69(d,J=7.8 Hz,4H),7.53–7.44(m,5H),7.37(t,J=7.2Hz,2H),7.32(d,J=6.9Hz,1H),6.99(s,2H),2.30(s,3H),2.07(s,6H). 13 C NMR (125 MHz, CDCl3) δ 142.95, 140.72, 138.59, 134.12, 133.18, 131.62, 131.37, 130.39, 129.10, 128.42, 127.95, 127.61, 126.53, 125.43, 125.05, 121.84, 119.20, 118.99, 117.09, 20.40, 16.99. HRMS for C 34 H 29 N2(M + The calculated value of 4-Cl) was 465.2325 and the found value was 465.2344.

[0590]

[0591]

[0266] 5-([1,1':3',1"-terphenyl]-5'-yl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (30). Prepared according to step 3 in general procedure B, reaction of 2-([1,1':3',1"-terphenyl]-5'-yl)-6-(1,3-dioxolan-2-yl)pyridine (379 mg, 1 mmol, 1 equiv), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 equiv), paraformaldehyde (45 mg, 1.5 mmol, 1.5 equiv) and 4M HCl in dioxane (1 mL, 4.0 mmol, 4 equiv) in toluene (5 mL) gave the title compound (500 mg) as a white solid in 92% yield. 1 H NMR(500MHz, CDCl3)δ9.30(s,1H),9.20(s,1H),8.90(d,J=9.5Hz,1H),8.24(s,1H),8.11(s,2H),7.97–7.90(m,4H),7.87–7.77(m,2 H),7.73–7.66(m,5H),7.62(d,J=7.6Hz,2H),7.55(d,J=7.9Hz,2H),2.58–2.44(m,2H),1.48(d,J=6.9Hz,6H),1.35(d,J=6.9Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 144.08, 143.00, 138.33, 133.72, 131.61, 131.43, 131.19, 129.65, 128.31, 127.82, 127.61, 126.36, 125.88, 124.67, 123.87, 121.91, 119.54, 119.22, 118.19, 27.88, 23.66, 23.55. HRMS for C 37 H 35 N2(M + The calculated value of 5-Cl) was 507.2795, and the found value was 507.2818.

[0592]

[0593]

[0146] 5-(2-Isopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (31). Prepared according to step 2 in general procedure A, reaction of 6-(2-isopropylphenyl)picolinaldehyde (225 mg, 1 mmol, 1 eq), 2,4,6-trimethylaniline (135 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (0.5 mL, 2.0 mmol, 2 eq) in toluene (5 mL) gave the title compound (317 mg) as a white solid in 81% yield. 1 H NMR(500MHz, CDCl3)δ9.23(s,1H),8.85(d,J=9.4Hz,1H),8.02(s,1H),7.58(t,J=6.7Hz,1H),7.52(d,J=7.7Hz,1H),7.47–7.38(m,3H),7.08 (d,J=6.8Hz,1H),6.99–6.95(m,2H),2.50–2.43(m,1H),2.31(s,3H),2.00(s,3H),1.94(s,3H),1.15(d,J=6.7Hz,3H),1.12(d,J=6.9Hz,3H). 13 C NMR (125 MHz, CDCl3) δ 147.90, 141.86, 134.17, 133.84, 133.79, 132.54, 132.22, 131.13, 129.99, 129.96, 129.80, 128.74, 127.82, 127.12, 125.48, 121.41, 121.19, 120.29, 119.39, 30.94, 25.20, 23.44, 21.21, 17.63, 17.25. HRMS for C 25 H 27 N2(M + The calculated value of 3-Cl) is 355.2169, and the found value is 355.2186.

[0594]

[0595]

[0266] 2-(2,6-Diisopropylphenyl)-5-(2-isopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (32). Prepared according to step 2 in general procedure A, reaction of 6-(2-isopropylphenyl)picolinaldehyde (225 mg, 1 mmol, 1 eq), 2,6-diisopropylaniline (177 mg, 1 mmol, 1.0 eq), paraformaldehyde (45 mg, 1.5 mmol, 1.5 eq) and 4M HCl in dioxane (0.5 mL, 2.0 mmol, 2 eq) in toluene (5 mL) gave the title compound (351 mg) as a white solid in 81% yield. 1 H NMR (500MHz, CDCl3) δ9.14(s,1H),8.85(d,J=9.3Hz,1H),7.97(s,1H),7.58–7.48(m,4H),7.38(t,J=7.5Hz,1H),7.31(d,J=7.6 Hz,1H),7.27–7.23(m,2H),7.11(d,J=6.9Hz,1H),2.55–2.49(m,1H),2.11–1.97(m,2H),1.20–1.06(m,12H),1.04–0.97(m,6H). 13 C NMR (125 MHz, CDCl3) δ 147.95, 145.02, 144.89, 133.56, 132.36, 132.27, 130.51, 129.51, 128.62, 127.78, 127.19, 126.02, 124.72, 124.64, 121.92, 121.02, 120.59, 120.00, 30.93, 28.83, 28.74, 24.96, 24.58, 24.26, 24.16, 23.58. HRMS for C 28 H 33 N2(M + The calculated value of 3-Cl) was 397.2638, and the found value was 397.2658.

[0596] 2,5-Dimesityl imidazo[1,5-a]pyridin-2-ium chloride (33)

[0597]

[0598] Step 1. Activated magnesium turnings (346 mg, 14.4 mol, 1.44 equiv) were suspended in anhydrous THF (10 mL). 2-Bromo-1,3,5-trimethylbenzene (478 mg, 2.4 mmol) was slowly added to the mixture at 60°C. The Grignard reaction was then initiated by the addition of catalytic 1,2-dibromoethane (approximately 80 μL). The remaining 2-bromo-1,3,5-trimethylbenzene (1.91 g, 9.6 mmol, 1.2 equiv total) was slowly added. After the addition was complete, the reaction mixture was heated at 60°C for 2 h. To a well-stirred suspension of 2-bromo-6-(1,3-dioxolan-2-yl)pyridine (2.3 g, 10 mmol, 1.0 equiv) and Ni(PCy3)Cl2 (69 mg, 0.1 mmol, 1 mol%) in anhydrous THF (5 mL) was slowly added the above Grignard solution over 10 minutes. The gained brown solution is heated at 50 DEG C for 12h, after which the mixture is poured onto NH4Cl aqueous solution (30mL). The aqueous layer is extracted with ethyl acetate (30mL×2), and the combined organic extracts are washed with salt water (30mL×2) and dried over anhydrous Na2SO4, filtered and concentrated in a vacuum. The residue is loaded onto a short silica gel pad. After washing with hexane, the residue is eluted with hexane / ethyl acetate (4 / 1) until the product is fully recovered. The filtrate is concentrated in a vacuum to obtain the desired product (2.47g) as a white solid in a yield of 91%. 1 H NMR (500MHz, CDCl3) δ7.80(t,J=7.7Hz,1H),7.52(d,J=7.8Hz,1H),7.22(d,J=7.6Hz ,1H),5.86(s,1H),4.28–4.15(m,2H),4.15–4.03(m,2H),2.31(s,3H),2.02(s,6H). 13 C NMR (125MHz, CDCl3) δ159.54,157.03,137.64,137.50,137.14,135.93,128.46,125.28,118.55,104.33,65.72,21.21,20.36.

[0599] Step 2. To a mixture of 2-(2,4,6-trimethylphenyl)-6-(1,3-dioxolane-2-yl)pyridine (2.15 g, 8 mmol, 1 equivalent), 2,4,6-trimethylaniline (1.08 g, 8 mmol, 1 equivalent), paraformaldehyde (360 mg, 12 mmol, 1.5 equivalents) in toluene (16 mL, 0.5 M) was added 4 M HCl (8 mL, 32 mmol, 4 equivalents) in dioxane. The mixture was then heated at 100 ° C for 12 h. The solvent was removed under reduced pressure. The residue was dried under high vacuum and then ground with ethyl acetate (15 mL) / hexane (5 mL) to obtain the desired product (3.06 g) as a white solid in 95% yield. The spectral data matched the literature value.

[0600]

[0601] 2-(2,6-Diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride (34). Prepared according to step 3 in general procedure B, reaction of 2-(2,4,6-trimethylphenyl)-6-(1,3-dioxolan-2-yl)pyridine (539 g, 2 mmol, 1 eq), 2,6-diisopropylaniline (354 mg, 2 mmol, 1.0 eq), paraformaldehyde (90 mg, 3 mmol, 1.5 eq) and 4M HCl in dioxane (2 mL, 8.0 mmol, 4 eq) in toluene (10 mL) gave the title compound (736 mg) as a white solid in 85% yield. Spectral data matched literature values.

[0602]

[0603] 2-Mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (35). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-triisopropylphenyl)pyridine (708 mg, 2 mmol, 1.0 eq), 2,4,6-trimethylaniline (270 mg, 2 mmol, 1 eq), paraformaldehyde (90 mg, 3 mmol, 1.5 eq) and 4M HCl in dioxane (2 mL, 8.0 mmol, 4 eq) in toluene (10 mL) gave the title compound (784 mg) as a white solid in 82% yield. Spectral data matched literature values.

[0604]

[0605] 2-(2,6-Diisopropylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (36). Prepared according to step 3 in general procedure B, reaction of 2-(1,3-dioxolan-2-yl)-6-(2,4,6-triisopropylphenyl)pyridine (708 mg, 2 mmol, 1.0 equiv), 2,6-diisopropylaniline (354 mg, 2 mmol, 1.0 equiv), paraformaldehyde (90 mg, 3 mmol, 1.5 equiv) and 4M HCl in dioxane (2 mL, 8.0 mmol, 4 equiv) in toluene (10 mL) gave the title compound (915 mg) as a white solid in 88% yield. Spectral data matched literature values.

[0606] Example 2: Representative gram-scale synthesis of NHC ligands

[0607] 5-(2,6-Diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride (9)

[0608]

[0609] Step 1. Activated magnesium turnings (1.38 g, 57.6 mol, 1.44 equivalents) were suspended in anhydrous THF (30 mL). 1-Bromo-2,6-diisopropylbenzene (2.32 g, 9.6 mmol) was slowly added to the mixture at 60°C. The Grignard reaction was then initiated by the addition of catalytic 1,2-dibromoethane (approximately 100 μL). The remaining 1-Bromo-2,6-diisopropylbenzene (9.26 g, 38.4 mmol, 1.2 equivalents total) was slowly added. After the addition was complete, the reaction mixture was heated at 60°C for 2 h. The above Grignard solution was slowly added to a well-stirred suspension of 2-bromo-6-(1,3-dioxolane-2-yl)pyridine (9.20 g, 40 mmol, 1.0 equiv) and Ni(PCy3)Cl2 (276 mg, 0.4 mmol, 1 mol%) in anhydrous THF (20 mL) over 15 minutes. The resulting brown solution was heated at 50 ° C for 12 h, after which the mixture was poured onto an NH4Cl aqueous solution (50 mL). The aqueous layer was extracted with ethyl acetate (100 mL × 2), and the combined organic extracts were washed with brine (100 mL × 2), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was loaded onto a short silica gel pad. After washing with hexane, the residue was eluted with hexane / ethyl acetate (4 / 1) until the product was completely recovered. The filtrate was concentrated in vacuo to give the desired product (12.10 g) as a white solid with a yield of 96%.

[0610] Step 2. To a mixture of 2-(2,6-diisopropylphenyl)-6-(1,3-dioxolane-2-yl)pyridine (9.34 g, 30 mmol, 1 equivalent), 2,4,6-trimethylaniline (4.05 g, 30 mmol, 1 equivalent), paraformaldehyde (1.35 g, 45 mmol, 1.5 equivalents) in toluene (60 mL, 0.5 M) was added 4 M HCl (30 mL, 120 mmol, 4 equivalents) in dioxane. The mixture was then heated at 100 ° C for 12 h. The solvent was removed under reduced pressure. The residue was dried under high vacuum and then ground with ethyl acetate (45 mL) / hexane (15 mL) to obtain the desired product (11.09 g) as a white solid in 89% yield. Spectral data matched the values ​​reported elsewhere herein.

[0611] 5-(2,6-diisopropyloxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (14)

[0612]

[0613] See the synthesis of 5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (14) as described elsewhere herein.

[0614] 2-(2,6-Bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (19)

[0615]

[0616] Step 1. Activated magnesium turnings (1.38 g, 57.6 mol, 1.44 equiv) were suspended in anhydrous THF (30 mL). 1-Bromo-2,4,6-triisopropylbenzene (2.72 g, 9.6 mmol) was slowly added to the mixture at 60°C. The Grignard reaction was then initiated by the addition of catalytic 1,2-dibromoethane (approximately 100 μL). The remaining 1-Bromo-2,4,6-triisopropylbenzene (10.88 g, 38.4 mmol, 1.2 equiv total) was slowly added. After the addition was complete, the reaction mixture was heated at 60°C for 2 h. The above Grignard solution was slowly added to a well-stirred suspension of 2-bromo-6-(1,3-dioxolane-2-yl)pyridine (9.20 g, 40 mmol, 1.0 equiv) and Ni(PCy3)Cl2 (276 mg, 0.4 mmol, 1 mol%) in anhydrous THF (20 mL) over 15 minutes. The resulting brown solution was heated at 50 ° C for 12 h, after which the mixture was poured onto an NH4Cl aqueous solution (50 mL). The aqueous layer was extracted with ethyl acetate (100 mL × 2), and the combined organic extracts were washed with brine (100 mL × 2), dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was loaded onto a short silica gel pad. After washing with hexane, the residue was eluted with hexane / ethyl acetate (4 / 1) until the product was completely recovered. The filtrate was concentrated in vacuo to give the desired product (12.08 g) as a white solid with a yield of 85%.

[0617] Step 2. To a mixture of 2-(2,4,6-triisopropylphenyl)-6-(1,3-dioxolane-2-yl)pyridine (7.07 g, 20 mmol, 1 eq), 2,6-bis(diphenylmethyl)-4-methylaniline (8.79 g, 20 mmol, 1 eq), paraformaldehyde (0.9 g, 30 mmol, 1.5 eq) in toluene (40 mL, 0.5 M) was added 4 M HCl (20 mL, 80 mmol, 4 eq) in dioxane. The mixture was then heated at 100 ° C for 12 h. The solvent was removed under reduced pressure. The residue was dried under high vacuum and then ground with ethyl acetate (60 mL) / hexane (20 mL) to obtain the desired product (14.15 g) as a white solid in 89% yield. The spectral data matched the values ​​reported in the previous section.

[0618] Example 3: Synthesis of imidazo[1,5-α]pyridine NHC ligand-metal complex

[0619] Cinnamyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (37)

[0620]

[0621] The corresponding NHC HCl salt (391 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (256 mg, 0.5 mmol, 0.5 equiv) were placed in an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 65% (398 mg). 1 H NMR(500MHz, CDCl3)δ7.37(s,1H),7.33(d,J=7.5Hz,1H),7.21–7.17(m,3H),7.06–7.01(m,4H),6.93–6.87(m,3H),6.35(d,J=6.6Hz,1H),4 .50–4.40(m,1H),4.04(d,J=12.5Hz,1H),3.06–3.00(m,1H),2.55(s, 1H),2.44(s,3H),2.40(s,3H),2.34(s,6H),1.91(s,3H),1.88(s,3H). 13 C NMR (125 MHz, CDCl3) δ 174.24, 139.78, 139.11, 139.05, 138.53, 138.46, 137.43, 136.84, 134.05, 133.72, 132.46, 129.95, 129.52, 128.22, 128.06, 127.52, 126.83, 122.66, 116.77, 115.70, 113.54, 109.88, 90.08, 60.53, 46.38, 21.82, 21.50, 21.29, 20.08, 19.46, 17.58. HRMS for C 34 H 35 N2Pd(M + The calculated value of -Cl) is 577.1842, the found value is 577.1855. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0622] Allyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (38)

[0623]

[0624] The corresponding NHC·HCl salt (391 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(allyl)Cl]2 (183 mg, 0.5 mmol, 0.5 equiv) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 78% (452 ​​mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 31 H 37 N2Pd(M + The calculated value of -Cl) is 543.1986, the found value is 543.1969. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0625] Cinnamyl[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (39)

[0626]

[0627] The corresponding NHC·HCl salt (433 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (256 mg, 0.5 mmol, 0.5 equiv) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 73% (478 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 37 H 41 N2Pd(M + The calculated value of -Cl) is 619.2313, the found value is 619.2333. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0628] 1-tert-Butyl-indenyl[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (40)

[0629]

[0630] The corresponding NHC HCl salt (433 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [(1-tBu-ind)PdCl] 2 (313 mg, 0.5 mmol, 0.5 equiv) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 37% (262 mg). 1 H NMR (500MHz, CDCl3) δ7.47(t,J=7.7Hz,1H),7.32–7.28(m,3H),7.12(s,1H),7.06(d,J=7.7Hz,2H),6. 95–6.89(m,2H),6.61(t,J=7.6Hz,1H),6.45–6.38(m,1H),6.23(t,J=7.2Hz,1H),5.76(d,J=7.0Hz,1H) ,5.22(d,J=3.0Hz,1H),4.77(s,1H),3.40–3.28(m,1H),2.66(s,3H),2.46(s,3H),1.86–1.75(m,4H),1 .41(d,J=6.8Hz,3H),1.29(s,9H),1.15(d,J=6.8Hz,3H),0.94(d,J=6.9Hz,3H),0.73(d,J=6.6Hz,3H). 13C NMR (125MHz, CDCl3) δ167.42,147.15,145.55,141.64,139.60,139.52,139.12,138.0 8,136.84,136.76,133.49,133.31,130.59,130.13,127.27,125.49,125.02,123.16,1 22.92,122.77,119.55,119.36,117.09,116.71,116.36,116.01,108.73,65.99,61.22,34.39,29.44,28.21,27.79,26.15,26.10,24.09,22.86,22.16,21.34,19.46,15.43. HRMS for C 41 H 47 N2Pd(M + The calculated value of -Cl) is 673.2784, the found value is 673.2762. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0631] Cinnamyl[2-mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (41)

[0632]

[0633] The corresponding NHC·HCl salt (475 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (256 mg, 0.5 mmol, 0.5 equiv) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 71% (495 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 40 H 47 N2Pd(M + The calculated value of -Cl) is 661.2783, the found value is 661.2807. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0634] Cinnamyl[5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium chloride (42)

[0635]

[0636] The corresponding NHC·HCl salt (433 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (256 mg, 0.5 mmol, 0.5 equiv) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 68% (445 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 37 H 41 N2Pd(M + The calculated value of -Cl) is 619.2313, the found value is 619.2331. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0637] Cinnamyl[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (43)

[0638]

[0639] The corresponding NHC·HCl salt (695 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (256 mg, 0.5 mmol, 0.5 equiv) were placed in an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with CHCl2 and eluted with CHCl2 through a short silica gel pad covered with a diatomaceous earth pad until the product was completely recovered. The solution was collected and concentrated. The desired product was obtained as a yellow solid after trituration with hexane and drying under high vacuum. Yield 85% (780 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 58 H 52 N2Pd(M+ The calculated value of -Cl) is 881.3101, the found value is 881.3170. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0640] Cinnamyl[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (44)

[0641]

[0642] The corresponding NHC·HCl salt (780 mg, 1.0 mmol, 1.0 equiv), KOtBu (157 mg, 1.4 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (256 mg, 0.5 mmol, 0.5 equiv) were placed in an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (10 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with CHCl2 and eluted with CHCl2 through a short silica gel pad covered with a diatomaceous earth pad until the product was completely recovered. The solution was collected and concentrated. The desired product was obtained as a yellow solid after grinding with hexane and drying under high vacuum. Yield 83% (832 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 64 H 63 N2Pd(M + The calculated value of -Cl) is 965.4042, the found value is 965.4097. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0643] Cinnamyl[5-(2,6-diisopropyloxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (45)

[0644]

[0645] The corresponding NHC·HCl salt (51 mg, 0.1 mmol, 1.0 equiv), KOtBu (15.7 mg, 0.14 mmol, 1.4 equiv) and [Pd(cin)Cl]2 (25.6 mg, 0.05 mmol, 0.5 equiv) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 72% (52.5 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 40 H 47 N2O2Pd(M + The calculated value of 4-Cl) was 693.2667, and the found value was 693.2689.

[0646] Pyridinium[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride (46)

[0647]

[0648] The corresponding NHC HCl salt (433 mg, 1.0 mmol, 1.0 equivalent), KOtBu (157 mg, 1.4 mmol, 1.4 equivalent) and PdCl2 (177 mg, 1.0 mmol, 1.0 equivalent) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Pyridine (5 mL) was added and the resulting reaction mixture was stirred at 80 ° C for 12 h. After cooling to room temperature, the reaction mixture was diluted with CHCl and passed through a short silica gel pad covered with a diatomaceous earth pad, eluted with CHCl until the product was completely recovered. The filtrate was concentrated in vacuo and purified via silica gel flash chromatography (hexane / ethyl acetate 10: 1 to 4: 1). The catalyst (496 mg, 76%) was obtained as a yellow solid. 1H NMR(500MHz, CDCl3)δ8.15(d,J=4.9Hz,2H),7.54(t,J=7.6Hz,1H),7.49(t,J=7.8Hz,1H),7.39(s,1H),7.31(d,J=7.6Hz,3H),7.10–7.02(m,4H) ,6.98(dd,J=9.2,6.7Hz,1H),6.60(dd,J=6.5,1.3Hz,1H),2.70(hept,J=6.7Hz,2H),2.30(s,9H),1.41(d,J=6.7Hz,6H),1.06(d,J=6.9Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 151.25, 146.85, 142.16, 139.82, 138.85, 138.63, 137.21, 135.71, 132.89, 132.62, 130.61, 128.63, 123.75, 123.70, 117.23, 117.11, 116.61, 28.79, 26.91, 23.24, 21.60, 21.34. HRMS for C 33 H 37 N3PdCl(M + The calculated value of 4-Cl) was 616.1714, and the found value was 616.1742.

[0649] 3-Chloropyridinium[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride (47)

[0650]

[0651] The corresponding NHC HCl salt (433 mg, 1.0 mmol, 1.0 equivalent), KOtBu (157 mg, 1.4 mmol, 1.4 equivalent) and PdCl2 (177 mg, 1.0 mmol, 1.0 equivalent) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. 3-Chloropyridine (5 mL) was added and the resulting reaction mixture was stirred at 80 ° C for 12 h. After cooling to room temperature, the reaction mixture was diluted with CHCl and passed through a short silica gel pad covered with a diatomaceous earth pad, eluted with CHCl until the product was completely recovered. The filtrate was concentrated in vacuo and purified via flash chromatography on silica gel (hexane / ethyl acetate 10: 1 to 4: 1). The catalyst (371 mg, 54%) was obtained as a yellow solid. 1HNMR(500MHz, CDCl3)δ8.19–8.13(m,2H),7.57–7.53(m,1H),7.50(t,J=7.8Hz,1H),7.40(s,1H),7.34–7.30(m,3H),7.06(s,2H),7.04 –6.98(m,2H),6.61(dd,J=6.7,1.3Hz,1H),2.72–2.63(m,2H),2.32(s,3H),2.29(s,6H),1.40(d,J=6.6Hz,6H),1.06(d,J=6.8Hz,6H). 13 CNMR (125 MHz, CDCl3) δ 150.30, 149.26, 146.84, 140.58, 139.81, 138.90, 138.78, 137.30, 135.61, 132.97, 132.53, 131.68, 130.68, 128.65, 124.12, 123.78, 122.98, 117.35, 117.24, 116.64, 28.80, 26.90, 23.22, 21.60, 21.34. HRMS for C 33 H 36 N3PdCl2(M + The calculated value of -Cl) is 650.1322, the found value is 650.1354. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solution.

[0652] 3-Chloropyridinium[2-mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride (48)

[0653]

[0654] The corresponding NHC HCl salt (475 mg, 1.0 mmol, 1.0 equivalent), KOtBu (157 mg, 1.4 mmol, 1.4 equivalent) and PdCl2 (177 mg, 1.0 mmol, 1.0 equivalent) were loaded into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. 3-Chloropyridine (5 mL) was added and the resulting reaction mixture was stirred at 80 ° C for 12 h. After cooling to room temperature, the reaction mixture was diluted with CHCl and passed through a short silica gel pad covered with a diatomaceous earth pad, eluted with CHCl until the product was completely recovered. The filtrate was concentrated in vacuo and purified via silica gel flash chromatography (hexane / ethyl acetate 10: 1 to 4: 1). The catalyst was obtained as a yellow solid. (453 mg, 62%). 1HNMR(500MHz, CDCl3)δ8.26(d,J=2.4Hz,1H),8.12(d,J=4.1Hz,1H),7.53(d, J=8.3Hz,1H),7.35(s,1H),7.33(d,J=9.3Hz,1H),7.19(s,2H),7.02–6.97(m, 3H),6.96–6.90(m,1H),6.68(d,J=6.2Hz,1H),3.05–2.97(m,1H),2.73–2.63 (m,2H),2.35(s,3H),2.21(s,6H),1.32–1.26(m,12H),1.05(d,J=6.7Hz,6H). 13 C NMR (125 MHz, CDCl3) δ 150.36, 150.29, 149.55, 149.09, 140.10, 139.44, 137.72, 137.35, 136.28, 136.16, 134.31, 131.65, 131.18, 129.20, 123.98, 122.09, 121.26, 119.35, 117.10, 115.35, 34.42, 31.52, 27.01, 24.27, 22.72, 21.39, 19.03. HRMS for C 36 H 42 N3PdCl2(M + The calculated value of 4-Cl) was 694.1788, and the found value was 694.1825.

[0655] 2-Dimethylaminomethylphenyl[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (49)

[0656]

[0657] The corresponding NHC HCl salt (390 mg, 0.5 mmol, 1.0 equiv), KOtBu (79 mg, 0.7 mmol, 1.4 equiv) and dimer [Pd(C6H4-CH2-NMe2)Cl]2 (138 mg, 0.25 mmol, 0.5 equiv) were placed in an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (5 mL, 0.1 M) was added, and the resulting reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with CHCl and passed through a short silica gel pad covered with a diatomaceous earth pad, eluted with CHCl until the product was completely recovered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 81% (413 mg). 1 HNMR(500MHz,CDCl3)δ7.74(d,J=6.7Hz,2H),7.26–7.22(m,3H),7.19–7.13(m,4H),7.06–7.01(m,3H),6.99(s,1H),6.96(d,J=7.1Hz,1H ),6.91(t,J=7.4Hz,2H),6.73–6.63(m,8H),6.61–6.55(m,2H),6.50–6.46(m,1H),6.43(d,J=5.7Hz,1H),6.35(d,J=7.1Hz,2H),5.79(s, 1H),5.50–5.44(m,2H),5.00(s,1H),3.64(d,J=14.3Hz,1H),3.36(d,J=14.4Hz,1H),2.97–2.91(m,1H),2.75–2.63(m,2H),2.43(s,3H), 2.18(s,3H),2.13(s,3H),1.69(d,J=6.6Hz,3H),1.29–1.27(m,6H),1.05(d,J=6.7Hz,3H),0.85(d,J=6.7Hz,3H),0.14(d,J=6.6Hz,3H). 13C NMR (125MHz, CDCl3) δ163.56,149.54,149.40,149.16,148.08,147.39,145.71,144.85,143.91,143.63,142.83,141.44, 138.43,137.62,136.48,136.17,131.61,131.39,131.16,130.13,129.63,129.46,129.41,128.07,128.04,127.28,126.2 5,126.01,125.61,125.58,124.08,121.63,121.59,120.92,119.84,119.78,119.50,117.56,72.73,51.73,51.05,50.08,49.87,34.50,32.08,31.88,31.41,29.85,29.81,29.51,28.06,25.27,24.75,23.71,22.84,22.44,22.04,20.75,14.27. Crystals suitable for X-ray crystallography were obtained from saturated hexane / DCM solutions. HRMS for C 64 H 66 N3Pd(M + The calculated value of 2-Cl) was 982.4386 and the found value was 982.4417.

[0658] 2-Acetamido-phenyl[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride (50)

[0659]

[0660] The corresponding NHC·HCl salt (390 mg, 0.5 mmol, 1.0 equiv), KOtBu (79 mg, 0.7 mmol, 1.4 equiv) and dimer [Pd(C6H4-NHC(O)Me)Cl]2 (138 mg, 0.25 mmol, 0.5 equiv) were charged into an oven-dried flask equipped with a stirring bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (5 mL, 0.1 M) was added and the resulting reaction mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with CHCl and eluted with CHCl through a short silica gel pad covered with a celite pad until the product was completely recovered. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 84% (428 mg). Due to the presence of different conformers, the NMR spectrum was too complex to analyze. HRMS for C 63 H 62 N3OPd(M + The calculated value of 1-Cl) was 982.3922 and the found value was 982.3963.

[0661] (2,5-Dimesityl imidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride (51)

[0662]

[0663] 2,5-dimesityl imidazo [1,5-a] pyridin-2-ium chloride (39 mg, 0.10 mmol, 1.0 equivalent), chloro (dimethyl sulfide) gold (I) (30 mg, 0.10 mmol, 1.0 equivalent) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under the positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH2Cl2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (54.6 mg) of a white solid was obtained in a yield of 93% from hexane by grinding. 1 H NMR(500MHz, CDCl3)δ7.45(d,J=9.2Hz,1H),7.26(s,1H),7.10–7.02(m,3H),6.92(s, 2H), 6.55 (dd, J=6.6, 1.4Hz, 1H), 2.41 (s, 3H), 2.31 (s, 3H), 2.07 (s, 6H), 1.94 (s, 6H). 13C NMR (125 MHz, CDCl3) δ 164.49, 140.95, 139.78, 138.74, 136.90, 136.25, 134.21, 131.67, 130.80, 129.44, 129.08, 123.61, 116.83, 116.34, 112.45, 21.58, 21.29, 20.03, 17.80. HRMS for C 25 H 30 N3AuClN2(M + +NH4) was calculated to be 604.1788, and the measured value was 604.1826.

[0664] (5-(2,6-diisopropylphenyl)-2-mesitylphenylimidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride (52)

[0665]

[0666] The corresponding NHC·HCl salt (43 mg, 0.10 mmol, 1.0 equiv), chloro(dimethyl sulfide)gold(I) (30 mg, 0.10 mmol, 1.0 equiv) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equiv) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (51.8 mg) was obtained as a white solid in 82% yield from hexane by grinding. 1 H NMR(500MHz, CDCl3)δ7.62(t,J=7.8Hz,1H),7.49(d,J=9.2Hz,1H),7.35–7.28(m,3H),7.10–7.04(m,1H),6.92(s,2H) ,6.57(d,J=6.6Hz,1H),2.42(p,J=6.9Hz,2H),2.29(s,3H),1.93(s,6H),1.28(d,J=6.9Hz,6H),1.14(d,J=6.8Hz,6H). 13C NMR (125 MHz, CDCl3) δ 165.10, 147.46, 139.68, 138.02, 136.33, 134.20, 131.61, 131.59, 131.00, 129.47, 123.95, 123.22, 117.04, 116.94, 112.44, 31.77, 25.30, 23.69, 21.25, 17.69. HRMS for C 28 H 33 N2AuClN2(M + The calculated value of H+H was 629.1992, and the measured value was 629.2015.

[0667] (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (53)

[0668]

[0669] The corresponding NHC·HCl salt (70 mg, 0.10 mmol, 1.0 equiv), chloro(dimethyl sulfide)gold(I) (30 mg, 0.10 mmol, 1.0 equiv) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equiv) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (86 mg) was obtained as a white solid in a 96% yield from hexane by grinding. 1 HNMR (500MHz, CDCl3) δ7.25–7.21(m,4H),7.19–7.14(m,8H),7.10(s,2H),7.07–7.04(m,4H),6.86–6.84(m,2H),6. 80–6.75(m,4H),6.66(s,2H),6.49–6.45(m,1H),5.70(s,1H),5.31(s,2H),2.47(s,3H),2.19(s,3H),2.08(s,6H). 13C NMR (125 MHz, CDCl3) δ 164.05, 142.59, 142.08, 141.03, 140.93, 139.78, 138.09, 136.90, 135.75, 130.73, 130.20, 129.87, 129.65, 129.24, 129.07, 128.59, 128.46, 126.71, 126.69, 122.71, 116.83, 116.41, 115.50, 51.66, 21.95, 21.60, 20.08. HRMS for C 49 H 43 N2AuCl(M + The calculated value of H (H) was 891.2775, and the found value was 891.2803.

[0670] (2-(2,6-bis(diphenylmethyl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (54)

[0671]

[0672] The corresponding NHC·HCl salt (71 mg, 0.10 mmol, 1.0 equiv), chloro(dimethyl sulfide)gold(I) (30 mg, 0.10 mmol, 1.0 equiv) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equiv) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (87 mg) was obtained as a white solid in a 96% yield from hexane by grinding. 1 HNMR(500MHz, CDCl3)δ7.26–7.21(m,4H),7.20–7.14(m,8H),7.11(s,2H),7.07(d,J=7.4Hz,4H),6.88–6.84(m,2H), 6.83–6.78(m,4H),6.50–6.45(m,1H),6.38(s,2H),5.69(s,1H),5.34(s,2H),3.53(s,3H),2.48(s,3H),2.09(s,6H). 13C NMR (125 MHz, CDCl3) δ 164.39, 159.83, 142.90, 142.32, 141.82, 140.87, 137.99, 136.87, 131.22, 130.71, 129.79, 129.58, 129.14, 129.03, 128.62, 128.47, 126.80, 126.76, 122.67, 116.81, 116.40, 115.74, 114.98, 55.16, 51.89, 21.58, 20.06. HRMS for C 49 H 43 N2OAuCl(M + The calculated value of H (H) was 907.2724 and the found value was 907.2763.

[0673] (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (55)

[0674]

[0675] The corresponding NHC·HCl salt (78 mg, 0.10 mmol, 1.0 equiv), chloro(dimethyl sulfide)gold(I) (30 mg, 0.10 mmol, 1.0 equiv) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equiv) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (91 mg) was obtained as a white solid in a 93% yield from hexane by grinding. 1 HNMR (500MHz, CDCl3) δ7.21–7.13(m,14H),7.07–7.03(m,4H),6.86–6.81(m,2H),6.80–6.74(m,4H),6.65(s,2H),6.53–6.48(m,1H),5.58( s,1H),5.24(s,2H),3.06–2.98(m,1H),2.53–2.42(m,2H),2.18(s,3H),1.41(d,J=7.0Hz,6H),1.29(d,J=7.0Hz,6H),1.15(d,J=6.7Hz,6H). 13C NMR (125 MHz, CDCl3) δ 164.66, 152.36, 147.03, 142.74, 142.34, 140.99, 139.82, 137.72, 135.83, 130.17, 129.73, 129.58, 129.18, 129.16, 128.56, 128.48, 126.68, 126.63, 122.34, 122.18, 117.15, 116.86, 115.71, 51.55, 34.87, 32.00, 25.31, 24.59, 24.07, 21.99. HRMS for C 55 H 55 N2AuCl(M + The calculated value of H (H) was 975.3714, and the found value was 975.3729.

[0676] (5-(2,6-diisopropyloxyphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (56)

[0677]

[0678] The corresponding NHC·HCl salt (51 mg, 0.10 mmol, 1.0 equivalent), chloro(dimethyl sulfide)gold(I) (30 mg, 0.10 mmol, 1.0 equivalent) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalent) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (61 mg) was obtained as a white solid in 87% yield from hexane by grinding. 1 HNMR (500MHz, CDCl3) δ7.50–7.40(m,3H),7.21(d,J=7.8Hz,2H),7.07(dd,J=9.1,6.7Hz,1H),6.64(d,J=8.5H z,2H),6.58(d,J=6.1Hz,1H),4.57–4.49(m,2H),2.28–2.18(m,2H),1.22–1.18(m,12H),1.14–1.09(m,12H). 13C NMR (125 MHz, CDCl3) δ 165.00, 157.52, 145.23, 135.93, 134.43, 131.77, 131.53, 130.49, 124.12, 123.97, 117.52, 116.28, 114.83, 113.04, 106.97, 70.98, 28.42, 24.80, 24.32, 22.79, 22.47. HRMS for C 31 H 38 AuN2O2(M + The calculated value of 4-Cl) was 667.2593, and the found value was 667.2624.

[0679] (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride (57)

[0680]

[0681] The corresponding NHC HCl salt (70 mg, 0.10 mmol, 1.0 equivalent), copper (I) chloride (19.8 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (71 mg) was obtained as a white solid in a yield of 94% from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.24–7.20(m,4H),7.18–7.13(m,8H),7.06(s,2H),7.00(d,J=7.5Hz,4H),6.95–6.91(m,1H),6.87–6.83( m,1H),6.82–6.75(m,4H),6.67(s,2H),6.42(d,J=6.4Hz,1H),5.93(s,1H),5.25(s,2H),2.44(s,3H),2.17(s,3H),2.01(s,6H). 13C NMR (125 MHz, CDCl3) δ 169.45, 142.80, 142.06, 141.00, 140.88, 139.61, 138.47, 136.22, 135.74, 130.11, 130.05, 130.00, 129.58, 129.54, 129.26, 128.67, 128.42, 126.64, 126.62, 122.87, 116.54, 115.23, 115.13, 51.68, 21.89, 21.58, 19.71. HRMS for C 49 H 42 N2Cu(M + The calculated value of 1-Cl) was 721.2139, and the found value was 721.2676.

[0682] (2-(2,6-bis(diphenylmethyl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride (58)

[0683]

[0684] The corresponding NHC HCl salt (71 mg, 0.10 mmol, 1.0 equivalent), copper (I) chloride (19.8 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (72 mg) was obtained as a white solid in a yield of 93% from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.25–7.20(m,4H),7.19–7.13(m,8H),7.07(s,2H),7.02(d,J=7.5Hz,4H),6.92(d,J=9.2Hz,1H),6.87–6.83 (m,1H),6.82–6.76(m,4H),6.43(d,J=6.6Hz,1H),6.38(s,2H),5.91(s,1H),5.27(s,2H),3.52(s,3H),2.45(s,3H),2.02(s,6H). 13C NMR (125 MHz, CDCl3) δ 168.91, 158.77, 141.79, 141.63, 140.82, 140.06, 137.50, 135.24, 130.27, 129.07, 128.97, 128.62, 128.53, 128.23, 127.77, 127.47, 125.77, 125.74, 121.84, 115.55, 114.42, 114.23, 113.95, 54.14, 50.97, 20.61, 18.75. HRMS for C 49 H 42 N2OCu(M + The calculated value of 1-Cl) was 737.2588, and the found value was 737.2630.

[0685] (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride (59)

[0686]

[0687] The corresponding NHC HCl salt (78 mg, 0.10 mmol, 1.0 equivalent), copper (I) chloride (19.8 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (74 mg) as a white solid was obtained in an 88% yield from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.25–7.14(m,14H),7.04–7.00(m,4H),6.87–6.83(m,2H),6.80–6.76(m,4H),6.67(s,2H),6.53–6.49(m,1H),5.64(s ,1H),5.19(s,2H),3.09–2.99(m,1H),2.54–2.44(m,2H),2.18(s,3H),1.41(d,J=6.9Hz,6H),1.23(d,J=6.9Hz,6H),1.17(d,J=6.8Hz,6H). 13C NMR (125 MHz, CDCl3) δ 169.52, 152.43, 146.68, 142.85, 142.38, 140.99, 139.64, 138.12, 135.81, 130.09, 129.74, 129.59, 129.14, 128.47, 128.44, 128.17, 126.65, 126.54, 122.75, 122.47, 116.61, 115.99, 115.82, 51.60, 34.80, 31.75, 25.21, 24.46, 24.43, 21.95. HRMS for C 55 H 54 N2Cu(M + The calculated value of 1-Cl) was 805.3578, and the found value was 805.3613.

[0688] (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride (60)

[0689]

[0690] The corresponding NHC·HCl salt (70 mg, 0.10 mmol, 1.0 equivalent) and silver (I) oxide (46 mg, 0.20 mmol, 2.0 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Dichloromethane (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (71 mg) was obtained as a white solid in 88% yield from hexane by grinding. 1 H NMR(500MHz, CDCl3)δ7.26–7.23(m,4H),7.21–7.16(m,8H),7.06–7.03(m,3H),6.97–6.90(m,5H),6.82–6.76 (m,4H),6.69(s,2H),6.48(d,J=6.4Hz,1H),6.19(s,1H),5.16(s,2H),2.45(s,3H),2.20(s,3H),1.96(s,6H). 13C NMR (125 MHz, CDCl3) δ 173.84 (d, J = 272.8 Hz), 173.84 (d, J = 237.0 Hz), 142.83, 141.81, 141.39, 140.87, 139.88, 138.46, 136.13, 135.98, 130.24, 129.53, 129.41, 129.30, 128.88, 128.48, 126.77, 126.73, 122.94, 116.74, 115.68, 115.47, 115.41, 51.61, 21.90, 21.65, 19.83. HRMS for C 49 H 42 N2Ag(M + The calculated value of 1-Cl) was 765.2393 and the found value was 765.2427.

[0691] (2-(2,6-bis(diphenylmethyl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride (61)

[0692]

[0693] The corresponding NHC·HCl salt (71 mg, 0.10 mmol, 1.0 equivalent) and silver (I) oxide (46 mg, 0.20 mmol, 2.0 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Dichloromethane (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (71 mg) was obtained as a white solid in 87% yield from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.26–7.23(m,4H),7.20–7.16(m,8H),7.07–7.02(m,3H),6.99–6.95(m,4H),6.93–6.88(m,1H),6.83– 6.77(m,4H),6.48(d,J=5.2Hz,1H),6.40(s,2H),6.17(d,J=1.8Hz,1H),5.18(s,2H),3.54(s,3H),2.45(s,3H),1.97(s,6H). 13C NMR (125 MHz, CDCl3) δ 174.24 (d, J = 273.4 Hz), 174.24 (d, J = 237.0 Hz), 159.85, 142.76, 142.60, 141.57, 141.37, 138.39, 136.13, 131.46, 130.60, 130.54, 129.52, 129.37, 129.22, 128.93, 128.51, 126.87, 126.81, 122.89, 116.73, 115.73, 115.66, 115.04, 55.17, 51.85, 21.65, 19.83. HRMS for C 49 H 42 N2OAg(M + The calculated value of 1-Cl) was 781.2343, and the found value was 781.2372.

[0694] (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride (62)

[0695]

[0696] The corresponding NHC·HCl salt (78 mg, 0.10 mmol, 1.0 equivalent) and silver (I) oxide (46 mg, 0.20 mmol, 2.0 equivalent) were loaded into an oven-dried flask equipped with a stir bar, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Dichloromethane (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (80 mg) was obtained as a white solid in a 90% yield from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.29–7.19(m,12H),7.18–7.13(m,2H),7.04–6.97(m,5H),6.96–6.90(m,1H),6.86–6.79(m,4H),6.74(s,2H),6.61– 6.56(m,1H),5.89(s,1H),5.14(s,2H),3.12–3.03(m,1H),2.56–2.44(m,2H),2.22(s,3H),1.45(d,J=7.2Hz,6H),1.18(d,J=4.1Hz,12H). 13C NMR (125MHz, CDCl3) δ173.39 (d, J = 270.5Hz), 173.39 (d, J = 234.7Hz), 172.38 (d, J = 17 .9Hz),152.43,146.72,142.78,142.11,140.89,139.88,137.89,136.01,130.37,130 .32,130.14,129.43,129.10,128.55,128.46,127.67,126.72,126.58,122.59,122.51,116.82,116.52,116.24,116.19,51.40,34.68,31.64,25.12,24.45,24.32,21.87. HRMS for C 55 H 54 N2Ag(M + The calculated value of -Cl) is 849.3332, and the found value is 849.3330.

[0697] Cyclooctadiene[5-(2,6-diisopropylphenyl)-2-mesitylphenylimidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride (63)

[0698]

[0699] The corresponding NHC HCl salt (43 mg, 0.10 mmol, 1.0 equivalent), [Rh (COD) Cl] 2 (24.6 mg, 0.05 mmol, 1.0 equivalent) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 53% (34 mg). 1H NMR (500MHz, CDCl3) δ7.58–7.48(m,2H),7.26–7.22(m,2H),7.18(d,J=7.5Hz,1H),7.13(s,1H),6.93(s,1H),6.79(dd,J=9.1,6.5 Hz,1H),6.40(d,J=6.0Hz,1H),4.60–4.52(m,1H),4.26–4.17(m,1H),3.76–3.67(m,1H),3.19–3.10(m,1H),2.88–2.80(m,1H),2.5 8(s,3H),2.38(s,3H),1.94–1.83(m,1H),1.77–1.72(m,1H),1.72(s,3H),1.61(d,J=6.6Hz,3H),1.56–1.51(m,1H),1.47–1.41(m, 1H),1.36–1.29(m,2H),1.25(d,J=6.7Hz,3H),1.21–1.16(m,1H),1.14–1.03(m,2H),1.00(d,J=6.9Hz,3H),0.81(d,J=6.7Hz,3H). 13 C NMR (125MHz, CDCl3) δ174.92 (d, J = 50.4Hz), 149.92, 147.13, 139.00, 138.03, 137.96, 137.2 0,134.99,134.45,134.06,129.99,129.83,127.79,124.62,122.35,121.68,117.80,117.19 ,114.72,93.54(d,J=9.1Hz),91.51(d,J=7.7Hz),69.68(d,J=14.1Hz),69.45(d,J=14.1Hz),32.58,31.73,31.15,30.23,27.96,27.79,27.73,26.04,23.89,22.02,21.20,20.36,17.34. HRMS for C 36 H 44 N2Rh(M + The calculated value of 4-Cl) was 607.2554, and the found value was 607.2559.

[0700] Dicarbonyl[5-(2,6-diisopropylphenyl)-2-mesitylphenylimidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride (64)

[0701]

[0702] In a 10mL vial, the corresponding (NHC)Rh(cod)Cl (32mg, 0.05mmol) was dissolved in dichloromethane (0.5mL). Carbon monoxide was bubbled into the solution for 3h at room temperature. The dichloromethane was then removed under vacuum. The product was obtained as a yellow solid from hexane by grinding. Yield 88% (26mg). 1 H NMR(500MHz,)δ7.49(t,J=7.8Hz,1H),7.44–7.39(m,2H),7.38(s,1H),7.28(d,J=7.6Hz,1H),7.02–6.93(m,3H),6.66(d,J=6.6Hz,1H),3.1 9–3.06(m,1H),2.35(s,3H),2.24(s,3H),2.00–1.93(m,1H),1.90(s,3H),1.50(d,J=6.6Hz,3H),1.22–1.16(m,6H),0.94(d,J=6.7Hz,3H). 13 C NMR (125 MHz, CDCl3) δ 185.49 (d, J = 55.4 Hz), 183.07 (d, J = 75.8 Hz), 169.69 (d, J = 45.0 Hz), 149.03, 147.54, 139.30, 137.30, 136.55, 135.52, 133.67, 132.71, 130.23, 129.87, 128.65, 124.07, 122.67, 122.16, 118.55, 117.10, 114.47, 31.83, 30.58, 27.30, 26.50, 23.63, 21.16, 19.17, 17.47. HRMS for C 30 H 32 N2O2Rh(M + The calculated value of 5-Cl) was 555.1513, and the found value was 555.1541.

[0703] Cyclooctadiene[2,5-dimesitylphenylimidazo[1,5-a]pyridin-2-ylidene]rhodium(I) chloride (65)

[0704]

[0705] The corresponding NHC HCl salt (39 mg, 0.10 mmol, 1.0 equivalent), [Rh (COD) Cl] 2 (24.6 mg, 0.05 mmol, 1.0 equivalent) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 61% (37 mg). 1 H NMR (500MHz, CDCl3) δ7.24–7.18(m,3H),7.14(s,1H),6.93(s,1H),6.89(s,1H),6.82(dd,J =9.2,6.6Hz,1H),6.32(d,J=6.0Hz,1H),4.56–4.49(m,1H),4.28–4.23(m,1H),3.29–3.22( m,1H),2.87–2.81(m,1H),2.69(s,3H),2.60(s,3H),2.43(s,3H),2.40(s,3H),1.75(s,3H) ,1.70(s,3H),1.58–1.54(m,2H),1.48–1.40(m,2H),1.31–1.25(m,2H),1.13–1.05(m,2H). 13 C NMR (125MHz, CDCl3) δ173.67 (d, J = 50.9Hz), 139.77, 138.97, 138.95, 138.27, 137.66, 1 37.11,136.90,134.83,133.65,133.56,129.74,129.51,127.67,127.58,122.41,116. 45,116.19,114.53,93.45(d,J=2.7Hz),93.38(d,J=4.5Hz),71.07(d,J=14.5Hz),67.11(d,J=14.5Hz),34.13,29.88,28.31,26.47,22.15,21.28,21.10,20.23,19.79,17.47. HRMS for C 33 H 38 N2Rh(M + The calculated value of 5-Cl) was 565.2085, and the found value was 565.2093.

[0706] Dicarbonyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-2-ylidene]rhodium(I) chloride (66)

[0707]

[0708] In a 10 mL vial, the corresponding (NHC)Rh(cod)Cl (30 mg, 0.05 mmol) was dissolved in dichloromethane (0.5 mL). Carbon monoxide was bubbled into the solution at room temperature for 3 h. The dichloromethane was then removed under vacuum. The product was obtained as a yellow solid from hexane by grinding. Yield 91% (25 mg). 1 H NMR(500MHz, CDCl3)δ7.38(d,J=9.2Hz,1H),7.36(s,1H),7.12(s,1H),7.01–6.95(m,4H),6.53( d,J=6.6Hz,1H),2.38(s,3H),2.35(s,3H),2.33(s,3H),2.19(s,3H),1.98(s,3H),1.92(s,3H). 13 C NMR (125 MHz, CDCl3) δ 185.11 (d, J = 55.4 Hz), 183.13 (d, J = 75.8 Hz), 168.48 (d, J = 45.0 Hz), 139.64, 139.55, 139.11, 138.89, 137.42, 136.68, 135.88, 133.74, 133.68, 131.57, 129.80, 129.51, 128.75, 128.15, 123.12, 116.72, 116.47, 114.38, 21.87, 21.33, 21.32, 20.25, 19.17, 17.61. HRMS for C 27 H 26 N2O2Rh(M + -Cl) was calculated to be 513.1044 and found to be 513.1067.

[0709] Cyclooctadiene[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride (67)

[0710]

[0711] The corresponding NHC HCl salt (78 mg, 0.10 mmol, 1.0 equivalent), [Rh (COD) Cl] 2 (24.6 mg, 0.05 mmol, 1.0 equivalent) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product was purified by silica gel column chromatography to obtain the desired product as a yellow solid. Yield 46% (46 mg). 1 H NMR (500MHz, CDCl3) δ7.51–7.43(m,3H),7.25–7.19(m,4H),7.19–7.02(m,9H),6.99(s,2H),6.96–6.88(m,4H),6.63(s,1H),6.50(d,J=6. 7Hz,2H),6.46(d,J=7.6Hz,1H),6.32(s,1H),6.31–6.28(m,1H),4.81–4.72(m,1H),4.69(s,2H),4.58–4.50(m,1H),3.93–3.83(m,1H),3.7 3–3.64(m,1H),3.41–3.33(m,1H),3.10–3.02(m,1H),2.28(s,3H),2.25–2.19(m,1H),1.78–1.69(m,2H),1.62(d,J=6.6Hz,4H),1.41(d,J =7.0Hz,6H),1.39–1.34(m,2H),1.29(d,J=6.7Hz,3H),1.27–1.26(m,2H),1.20(d,J=6.7Hz,3H),0.87–0.84(m,2H),0.79(d,J=6.7Hz,3H). 13C NMR (125MHz, CDCl3) δ172.07 (d, J = 50.4Hz), 149.76, 149.73, 146.34, 145.19, 144.52, 143.86, 143.84, 142.42, 142.31, 138.61, 137.55, 137.00,132.91,131.52,130.45,130.41,130.04,129.82,129.02,128.60,128.44,128.10,127.97,127.91,126.63,126.59,125.99,125 .93,123.05,120.14,119.40,119.05,117.42,94.01(d,J=6.8Hz),93.48(d,J=8.2Hz),71.46(d,J=14.1Hz),66.54(d,J=14.1Hz),51.99,50.34,34.82,34.62,33.98,31.74,31.51,30.72,29.86,28.76,27.97,26.94,25.45,24.24,24.17,24.06,22.80,22.62,21.97,14.27. 63 H 66 N2Rh(M + The calculated value of 1-Cl) was 953.4276 and the found value was 953.4283.

[0712] Dicarbonyl[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride (68)

[0713]

[0714] In a 10mL vial, the corresponding (NHC)Rh(cod)Cl (40mg, 0.04mmol) was dissolved in dichloromethane (0.4mL). Carbon monoxide was bubbled into the solution at room temperature for 24h. The dichloromethane was then removed under vacuum. The product was obtained as a yellow solid from hexane by grinding. Yield 90% (38mg). 1H NMR (500MHz, CDCl3) δ7.32 (s, 1H), 7.26–7.05 (m, 15H), 6.99 (d, J = 7.5Hz, 2H), 6.86–6.79 (m, 2 H),6.73(s,1H),6.71–6.67(m,1H),6.65(s,1H),6.59(d,J=6.6Hz,1H),6.57–6.48(m,3H),6. 40(s,1H),5.03(s,1H),4.86(s,1H),3.27–3.16(m,1H),3.05–2.96(m,1H),2.26–2.17(m,4H) ,1.55(d,J=6.6Hz,3H),1.34(dd,J=7.0,3.8Hz,6H),1.23–1.16(m,6H),0.94(d,J=6.7Hz,3H). 13 C NMR (125MHz, CDCl3) δ185.90 (d, J = 55.9Hz), 183.79 (d, J = 75.4Hz), 167.85 (d, J = 44.1Hz), 151.03, 149.31, 147. 07,144.50,143.51,143.25,142.26,141.81,139.07,136.94,136.69,131.29,130.78,130.46,130.32,129.91 ,129.87,129.80,129.16,128.25,128.12,128.06,127.92,126.78,126.57,126.24,126.04,122.33,121.02,120.75,119.22,118.77,117.19,51.62,50.03,34.86,31.69,31.00,27.57,26.46,24.27,23.89,21.93,21.90. HRMS for C 57 H 54 N2O2Rh(M + The calculated value of HCl was 901.3235 and the found value was 901.3260.

[0715] 2,5-Dimesityl imidazo[1,5-a]pyridine-3(2H)-selensulfone (69)

[0716]

[0717] 2,5-di-mesitylphenylimidazo [1,5-a] pyridine -2- ium chloride (39 mg, 0.10 mmol, 1.0 equivalent), selenium (16 mg, 0.20 mmol, 2.0 equivalent) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalent) were loaded into an oven-dried flask equipped with a stirring rod, placed under the positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH2Cl2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (39.4 mg) in a yellow solid yield of 91% was obtained from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.23 (d, J = 9.3Hz, 1H), 7.13 (s, 1H), 6.96 (s, 2H), 6.87 (s, 2H), 6.84 –6.78(m,1H),6.27(d,J=6.4Hz,1H),2.33(s,3H),2.32(s,3H),2.09(s,6H),1.95(s,6H). 13 C NMR (125MHz, CDCl3) δ147.92,139.68,139.18,138.56,137.69,135.22,134.99,131.59 ,131.18,129.29,127.31,122.59,117.24,115.77,109.81,21.46,21.37,20.97,18.29. 77 Se NMR (95MHz, CDCl3) δ 100.66. HRMS for C 25 H 27 N2Se(M + The calculated value of H (H) was 434.1257, and the found value was 434.1274.

[0718] 5-(2,6-Diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridine-3(2H)-selensulfone(70)

[0719]

[0720] The corresponding NHC HCl salt (43 mg, 0.10 mmol, 1.0 equivalent), selenium (16 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (44.8 mg) was obtained as a yellow solid in a yield of 94% from hexane by grinding. 1 H NMR(500MHz, CDCl3)δ7.40(t,J=7.7Hz,1H),7.25(d,J=11.4Hz,1H),7.18–7.08(m,3H),6.96(s,2H),6.77(dd,J=9.1,6.6 Hz,1H),6.26(d,J=6.3Hz,1H),2.68–2.53(m,2H),2.31(s,3H),1.94(s,6H),1.28(d,J=6.9Hz,6H),1.13(d,J=6.8Hz,6H). 13 C NMR (125MHz, CDCl3) δ147.84,139.09,139.06,135.11,135.09,131.84,130.96,12 9.48,129.25,121.96,117.48,116.16,109.67,31.76,25.26,22.53,21.33,18.25. 77 Se NMR (95MHz,CDCl3)δ144.89. HRMS for C 28 H 33 N2Se(M + The calculated value of H (H) was 477.1805, and the found value was 477.1825.

[0721] 2-(2,6-Bisdiphenylmethyl-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridine-3(2H)-selensulfone (71)

[0722]

[0723] The corresponding NHC HCl salt (70 mg, 0.10 mmol, 1.0 equivalent), selenium (16 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (67 mg) of a yellow solid was obtained in a yield of 91% from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.25–7.21(m,8H),7.18–7.13(m,8H),6.97(s,2H),6.82(d,J=5.7Hz,4H),6.70(s,2H),6.57–6.52( m,1H),6.51–6.47(m,1H),6.18(dd,J=6.3,1.5Hz,1H),5.27(s,1H),5.23(s,2H),2.42(s,3H),2.21(s,6H),2.20(s,3H). 13 C NMR (125MHz, CDCl3) δ146.98,143.03,142.34,142.02,138.87,138.78,138.55,137.88,134.50,131.88,130.10,129.96 ,129.32,129.14,128.27,128.24,127.32,126.46,126.41,121.20,117.33,115.68,113.20,52.21,21.99,21.57,21.06. 77 Se NMR (95MHz, CDCl3) δ 119.35. HRMS for C 49 H 43 N2Se(M + The calculated value of H (H) was 739.2586, and the found value was 739.2603.

[0724] 2-(2,6-Bis-diphenylmethyl-4-methoxyphenyl)-5-mesityl imidazo[1,5-a]pyridine-3(2H)-selensulfone (72)

[0725]

[0726] The corresponding NHC HCl salt (71 mg, 0.10 mmol, 1.0 equivalent), selenium (16 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (69 mg) of a yellow solid was obtained in a yield of 92% from hexane by grinding. 1 H NMR(500MHz, CDCl3)δ7.23–7.19(m,8H),7.17–7.12(m,8H),6.96(s,2H),6.84–6.79(m,4H),6.55–6.50(m,1H),6.49 –6.45(m,1H),6.40(s,2H),6.16(d,J=6.3Hz,1H),5.24(s,1H),5.21(s,2H),3.53(s,3H),2.41(s,3H),2.19(s,6H). 13 C NMR (125MHz, CDCl3) δ159.39,147.40,143.88,142.79,142.13,138.88,138.58,137.90,131.92,130.03,129.93,129 .27,129.08,128.31,127.34,126.61,126.49,121.17,117.34,115.69,114.86,113.47,55.11,52.42,21.58,21.07. 77 SeNMR (95MHz,CDCl3)δ118.02.HRMS for C 49 H 43 N2SeO(M + The calculated value of H (H) was 755.2535 and the found value was 755.2544.

[0727] 2-(2,6-Bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridine-3(2H)-selensulfone(73)

[0728]

[0729] The corresponding NHC HCl salt (78 mg, 0.10 mmol, 1.0 equivalent), selenium (16 mg, 0.20 mmol, 2.0 equivalents) and KOtBu (16.8 mg, 0.15 mmol, 1.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. THF (1.0 mL, 0.10 M) was added and the resulting solution was stirred at room temperature for 12 h. The reaction mixture was diluted with CH 2 Cl 2 and filtered through diatomaceous earth. The solution was collected and concentrated. The product (77 mg) of a yellow solid was obtained in a yield of 94% from hexane by grinding. 1 H NMR (500MHz, CDCl3) δ7.23–7.17(m,8H),7.16–7.10(m,8H),7.02(s,2H), 6.81(d,J=6.5Hz,4H),6.68(s,2H),6.48(s,2H),6.24–6.19(m,1H),5.26( s,1H),5.19(s,2H),3.01(p,J=7.0Hz,1H),2.73(p,J=6.7Hz,2H),2.18(s ,3H),1.37(d,J=6.9Hz,6H),1.35(d,J=6.9Hz,6H),1.16(d,J=6.8Hz,6H). 13 C NMR (125MHz, CDCl3) δ150.01,148.34,147.55,143.05,142.67,141.93,138.72,138.68,134.59,130.03,129.94,129.39,129.28,1 29.01,128.27,128.19,126.39,126.34,120.68,120.10,117.31,116.13,112.80,52.22,34.45,31.99,25.20,24.35,22.88,22.01. 77 Se NMR (95MHz,CDCl3)δ170.40. HRMS for C 55 H 55 N2Se(M + The calculated value of H (H) was 823.3525, and the found value was 822.3549.

[0730] (5-(2,4,6-triethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (74)

[0731]

[0732] The corresponding NHC·HCl salt (47.5 mg, 0.10 mmol, 1.0 equivalent), chloro(dimethyl sulfide)gold(I) (29.5 mg, 0.1 mmol, 1.0 equivalent) and potassium carbonate (27.6 mg, 0.2 mmol, 2 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Acetone (1.0 mL, 0.10 M) was added and the resulting solution was heated and stirred at 60 ° C for 24 h. The reaction mixture was diluted with CHCl and filtered through diatomaceous earth. The solution was collected and concentrated. The residue was loaded onto a short silica gel pad and eluted with CHCl until the product was fully recovered. After grinding with pentane and drying under high vacuum, the desired product was obtained as a white solid. Yield 83% (55.8 mg). 1 H NMR(500MHz, CDCl3) δ7.48(d,J=8.4Hz,1H),7.44(t,J=7.8Hz,1H),7.32(s,1 H),7.20(d,J=7.8Hz,2H),7.11(s,2H),7.10–7.06(m,1H),6.62(dd,J=6.6,1. 1Hz,1H),2.74(q,J=7.6Hz,2H),2.50–2.42(m,2H),2.32–2.25(m,2H),2.17–2 .10(m,2H),1.34(t,J=7.6Hz,3H),1.21(d,J=6.8Hz,6H),1.15–1.10(m,12H). 13 C NMR (125 MHz, CDCl3) δ 166.05, 147.47, 145.16, 142.60, 138.29, 135.68, 131.35, 130.71, 129.83, 126.39, 124.16, 123.59, 117.05, 116.90, 113.62, 29.09, 28.62, 26.82, 24.46, 15.50. HRMS for C 31 H 39 AuN2Cl(M + The calculated value of H (+H) was 670.2384, the found value was 670.2415; the calculated value of H (+H) was 672.2357, the found value was 672.2383.

[0733] Cinnamyl (5-(2,4,6-triethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)palladium(II) chloride (75)

[0734]

[0735] The corresponding NHC HCl salt (998 mg, 2.1 mmol, 1.05 equivalents), KOtBu (314 mg, 2.8 mmol, 1.4 equivalents) and [Pd (cin) Cl] 2 (518 mg, 1 mmol, 0.5 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Anhydrous tetrahydrofuran (20 mL) was added, and the resulting reaction mixture was stirred at room temperature for 4 h. The reaction mixture was diluted with CH 2 Cl 2 and passed through a short diatomaceous earth pad. The solution was collected and concentrated. The residue was loaded onto a short silica gel pad and eluted with hexane / ethyl acetate (4: 1) until the product was fully recovered. After grinding with pentane and drying under high vacuum, the desired product was obtained as a yellow solid. Yield 79% (1.1 g). NMR data were obtained at -30 ° C. 1 H NMR showed the presence of two isomers with a ratio of 3:7 between the two isomers. 1 H NMR (500 MHz, CDCl 3, 243K)δ7.52–7.39(m,2H),7.39–7.30(m,2H),7.28–7.12(m,5H),7.03–6.84(m,4H),6.57(d,J=6.4Hz,0.3H),6.47(d,J=6.5Hz,0.7H), 4.79–4.68(m,0.3H),4.31–4.21(m,0.7H),3.90(d,J=12.5Hz,0.7H),3.22(d,J=12.6Hz,0.3H),3.20–3.13(m,0.7H),3.12–3.06(m,0.3 H),3.04–2.98(m,0.3H),2.96–2.88(m,0.7H),2.86–2.65(m,4H),2.26–2.15(m,1H),2.14–2.08(m,0.7H),2.06–2.00(m,0.3H),1.97– 1.86(m,1H),1.47–1.38(m,1H),1.36(t,J=7.6Hz,2H),1.33–1.19(m,8H),1.15(t,J=7.5Hz,2H),1.10–1.03(m,8H),1.01–0.92(m,1H). 13C NMR (126MHz, CDCl3, 243K) δ175.56,175.28,147.17,146.06,145.19,144.88,144.80,144.60,144.45,142.46,141.92,138.43,138.30,1 38.03,137.84,136.84,136.73,132.54,131.42,131.04,129.98,129.86,128.25,128.02,127.33,126.88,126.58,126.08,125.73,124. 29,124.01,122.94,122.79,122.63,122.56,116.69,116.08,115.69,115.37,109.55,108.14,90.16,89.54,47.66,46.25,28.99,28.93,28.59,28.36,28.24,28.10,27.89,27.27,26.96,26.67,25.61,25.48,23.32,22.76,22.29,22.03,16.49,15.50,15.23,14.24,14.10. 40 H 48 N2PdCl(M + The calculated value of H (+H) was 719.2366, the found value was 719.2341; 721.2359, the found value was 719.2328.

[0736] (5-(2,4,6-Trimethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (76)

[0737]

[0738] The corresponding NHC HCl salt (43 mg, 0.1 mmol, 1.0 equivalent), chloro(dimethyl sulfide)gold(I) (30 mg, 1 mmol, 1.0 equivalent) and potassium carbonate (42 mg, 0.3 mmol, 3 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Acetone (1 mL, 0.10 M) was added and the resulting solution was heated and stirred at 60 ° C for 3 h. The reaction mixture was diluted with CH2Cl2 and filtered through diatomaceous earth. The solution was collected and concentrated. The residue was loaded onto a short silica gel pad and eluted with CH2Cl2 until the product was fully recovered. After grinding with pentane and drying under high vacuum, the desired product was obtained as a white solid. Yield 74% (46 mg). 1 H NMR(500MHz, CDCl3)δ7.49–7.43(m,2H),7.32(s,1H),7.21(d,J=7.8Hz,2H),7.11–7.07(m,1H),7.05(s,2H),6.58 (dd,J=6.6,1.2Hz,1H),2.41(s,3H),2.18–2.12(m,2H),2.08(s,6H),1.23(d,J=6.9Hz,6H),1.12(d,J=6.9Hz,6H). 13 C NMR (126MHz, CDCl3) δ165.55,145.18,141.00,138.73,136.91,135.60,131.34,130.75 ,129.09,124.17,123.88,116.81,116.51,113.70,28.60,24.51,24.47,21.55,19.95.

[0739] (5-(2,6-diisopropylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (77)

[0740]

[0741] The corresponding NHC HCl salt (48 mg, 0.1 mmol, 1.0 equivalent), chloro(dimethyl sulfide)gold(I) (30 mg, 1 mmol, 1.0 equivalent) and potassium carbonate (42 mg, 0.3 mmol, 3 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Acetone (1 mL, 0.10 M) was added and the resulting solution was heated and stirred at 60 ° C for 4 h. The reaction mixture was diluted with CH Cl and filtered through diatomaceous earth. The solution was collected and concentrated. The residue was loaded onto a short silica gel pad and eluted with CH Cl until the product was fully recovered. After grinding with pentane and drying under high vacuum, the desired product was obtained as a white solid. Yield 78% (52 mg). 1 H NMR (500MHz, CDCl3) δ7.62(t,J=7.8Hz,1H),7.50(dd,J=9.3,1.1Hz,1H),7.44(t,J =7.8Hz,1H),7.34(s,1H),7.31(d,J=7.9Hz,2H),7.21(d,J=7.8Hz,2H),7.13–7.08 (m,1H),6.60(dd,J=6.6,1.2Hz,1H),2.46–2.39(m,2H),2.18–2.10(m,2H),1.27(d ,J=6.9Hz,6H),1.20(d,J=6.8Hz,6H),1.15(d,J=6.8Hz,6H),1.12(d,J=6.9Hz,6H). 13 C NMR (126MHz, CDCl3) δ166.22,147.46,145.13,138.03,135.63,131.53,131.30,131.08,130.6 9,124.20,123.97,123.48,117.09,117.03,113.59,31.88,28.63,25.34,24.58,24.33,23.60.

[0742] (5-(2,6-Diisopropylphenyl)-2-cyclohexyl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride (78)

[0743]

[0744] The corresponding NHC HCl salt (40 mg, 0.1 mmol, 1.0 equivalent), chloro(dimethyl sulfide)gold(I) (30 mg, 1 mmol, 1.0 equivalent) and potassium carbonate (42 mg, 0.3 mmol, 3 equivalents) were loaded into an oven-dried flask equipped with a stirring rod, placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Acetone (1 mL, 0.10 M) was added and the resulting solution was heated and stirred at 60 ° C for 8 h. The reaction mixture was diluted with CH Cl and filtered through diatomaceous earth. The solution was collected and concentrated. The residue was loaded onto a short silica gel pad and eluted with CH Cl until the product was fully recovered. After grinding with pentane and drying under high vacuum, the desired product was obtained as a white solid. Yield 53% (31 mg). 1 H NMR(500MHz, CDCl3)δ7.63(t,J=7.8Hz,1H),7.43(s,1H),7.40(d,J=9.2Hz,2H),7.33 (d,J=7.9Hz,2H),7.01–6.94(m,1H),6.48(d,J=6.4Hz,1H),4.98–4.88(m,1H),2.36–2 .27(m,2H),2.18–2.12(m,2H),1.91–1.84(m,2H),1.80–1.73(m,1H),1.73–1.61(m,2H ),1.54–1.42(m,2H),1.26(d,J=6.9Hz,7H),1.24–1.17(m,1H),1.09(d,J=6.8Hz,6H). 13 C NMR (126MHz, CDCl3) δ162.37,147.58,137.53,131.73,131.50,130.93,123.95,1 22.74,116.90,116.76,107.92,63.20,34.48,31.63,25.41,25.39,25.27,23.77.

[0745] Example 4: Catalysis

[0746] General Procedure for the Suzuki-Miyaura Cross-Coupling of Nitroarenes Using the [Pd(NHC)(allyl)Cl] Complex (General Procedure I)

[0747]

[0748] An oven-dried vial equipped with a stir bar was charged with nitroarene (neat, 1.0 equiv), boronic acid (typically, 1.5 equiv), K3PO4 (typically, 3.0 equiv), Pd-NHC catalyst (typically, 5 mol%), water (typically, 3 equiv), TDA (typically, 10 mol%), placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, dioxane (typically 0.2 M) was added at room temperature, and the reaction mixture was placed in a preheated oil bath (typically, 130°C) and stirred for 15 h. After 15 h, the reaction mixture was cooled to room temperature, diluted with CH2Cl2 (10 mL), filtered, and concentrated. 1 The samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion and yield. Purification by silica gel chromatography afforded the product.

[0749] Synthesis of 4-methoxybiphenyl (General Procedure I)

[0750]

[0751] According to the general procedure, nitrobenzene (0.2 mmol), 4-methoxyphenylboronic acid (1.5 equiv), K 3 PO 4 (3.0 equiv), 39 (5 ​​mol%), water (3 equiv) and TDA (10 mol%) were reacted at 130° C. for 16 h to provide the title compound (32.4 mg) in 88% yield after work-up and chromatography as a white solid. 1 H NMR (500MHz, CDCl3) δ7.59–7.51(m,4H),7.42(t,J=7.7Hz,2H),7.30(t,J=7.4Hz,1H),6.98(d,J=8.7Hz,2H),3.86(s,3H). 13 C NMR (125MHz, CDCl3) δ159.30,140.99,133.94,128.86,128.30,126.89,126.80,114.35,55.50.

[0752] General procedure for the Suzuki-Miyaura cross-coupling of nitroarenes using the [Pd(NHC)(py)Cl2] complex (General procedure II)

[0753]

[0754] An oven-dried vial equipped with a stir bar was charged with nitroarene (neat, 1.0 equiv), boronic acid (typically, 1.5 equiv), K3PO4 (typically, 3.0 equiv), Pd-NHC catalyst (typically, 5 mol%), water (typically, 3 equiv), TDA (typically, 10 mol%), placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, dioxane (typically 0.2 M) was added at room temperature, and the reaction mixture was placed in a preheated oil bath (typically, 130°C) and stirred for 15 h. After 15 h, the reaction mixture was cooled to room temperature, diluted with CH2Cl2 (10 mL), filtered, and concentrated. 1 The samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion and yield. Purification by silica gel chromatography (EtOAc / hexanes) afforded the product.

[0755] Synthesis of 4-methoxybiphenyl (General Procedure II)

[0756]

[0757] According to the general procedure, nitrobenzene (0.2 mmol), 4-methoxyphenylboronic acid (1.5 equiv), K 3 PO 4 (3.0 equiv), 47 (5 mol%), water (3 equiv) and TDA (10 mol%) were reacted at 130° C. for 36 h to afford the title compound (26.1 mg) in 71% yield after workup and chromatography as a white solid. 1 H NMR (500MHz, CDCl3) δ7.61–7.51(m,4H),7.42(t,J=7.7Hz,2H),7.31(t,J=7.3Hz,1H),6.99(d,J=8.8Hz,2H),3.86(s,3H). 13 C NMR (125MHz, CDCl3) δ159.30,140.98,133.94,128.86,128.30,126.89,126.80,114.35,55.49.

[0758] General Procedure for Amination of Alkyl Sulfoxides (General Procedure III)

[0759]

[0760] An oven-dried vial equipped with a stir bar was charged with sulfoxide (neat, 1.0 equiv), aniline (typically 1.5 equiv), [Pd(cin)Cl]2 (typically 2.5 mol%), Pd-NHC catalyst (typically 10 mol%), placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, THF (typically 0.2 M) and LiHMDS in THF (typically 2 equiv) were added at room temperature, and the reaction mixture was placed in a preheated oil bath (typically 100°C) and stirred for 12 h. After 12 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. 1 Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0761] Synthesis of 4-methyl-N-phenylaniline (General Procedure III)

[0762]

[0763] An oven-dried vial equipped with a stir bar was charged with methylphenylsulfoxide (28 mg, 0.2 mmol, 1.0 equiv), p-toluidine (32 mg, 0.3 mmol, 1.5 equiv), [Pd(cin)Cl]2 (2.6 mg, 0.005 mmol, 2.5 mol%), and 9 (8.7 mg, 0.02 mmol, 10 mol%), placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, THF (1 mL, 0.2 M) and 1 M LiHMDS in THF (0.4 mL, 0.4 mmol, 2 equiv) were added at room temperature. The reaction mixture was placed in a preheated oil bath and stirred at 100°C for 12 h. After 12 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL), and extracted with ethyl acetate (2 x 5 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product (31.5 mg) in 86% yield as a white solid. 1 H NMR (500MHz, CDCl3) δ7.25–7.19(m,2H),7.07(d,J=8.2Hz,2H),7.02–6.95(m,4H),6.86(t,J=7.3Hz,1H),5.64(s,1H),2.29(s,3H).13 C NMR (125MHz, CDCl3) δ144.06,140.39,131.11,130.00,129.45,120.47,119.06,117.02,20.83.

[0764] General Procedure for the Amination of Thiophenols (General Procedure IV)

[0765]

[0766] In an oven-dried vial equipped with a stirring bar, thiophenol (neat, 1.0 equiv), aniline (typically, 2 equiv), Pd-NHC catalyst (typically, 5 mol%) were charged, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, toluene (typically, 0.2 M) and LiHMDS in toluene (typically, 4 equiv) were added at room temperature, and the reaction mixture was placed in a preheated oil bath (typically, 130° C.) and stirred for 12 h. After 12 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over anhydrous Na 2 SO 4 and concentrated under reduced pressure. 1 Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0767] Synthesis of 2-methyl-N-phenylaniline (General Procedure IV)

[0768]

[0769] Thiophenol (22 mg, 0.2 mmol, 1.0 equiv.), o-toluidine (43 mg, 0.4 mmol, 2 equiv.), 37 (6.1 mg, 0.01 mmol, 5 mol%) were charged into an oven-dried vial equipped with a stirring bar, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Under vigorous stirring, toluene (1 mL, 0.2 M) and 1 M LiHMDS (0.8 mL, 0.8 mmol, 4 equiv.) in toluene were added, the reaction mixture was placed in a preheated oil bath and stirred at 130 ° C for 12 h. After 12 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2 × 5 mL). The combined organic layers were dried over anhydrous Na SO and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexane) provided the title product (29.7 mg) in 85% yield. White solid.1 H NMR (500MHz, CDCl3) δ7.26–7.20(m,3H),7.18(d,J=6.8Hz,1H),7.12(t,J=7.7Hz,1H),6.98–6.82(m,4H),5.37(s,1H),2.24(s,3H). 13 C NMR (125MHz, CDCl3) δ144.10,141.34,131.08,129.45,128.42,126.90,122.12,120.62,118.91,117.60,18.04.

[0770] General Procedure for Monoarylation of Hydrines (General Procedure V)

[0771]

[0772] Halobenzene (neat, 1.0 equiv), Pd-NHC catalyst (typically, 5 mol%) and rubidium carbonate (typically, 3 equiv) were charged into an oven-dried vial equipped with a stir bar, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Dioxane (typically, 0.1 M) and hydrazine monohydrate (typically, 5 equiv) were then added to the reaction, and the reaction was heated at 120 ° C for 12 h. After the indicated time, acetylacetone (typically, 9.0 equiv) and 2M TFA in EtOH (typically, 4 equiv) were added to the reaction. The reaction was then heated at 100 ° C for 6 h under stirring. The reaction mixture was then diluted with CH2Cl2 (10 mL), filtered, and concentrated. By 1 Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0773] Synthesis of 1-(4-methoxyphenyl)-3,5-dimethyl-1H-pyrazole (General Procedure V)

[0774]

[0775] In the oven-dried vial equipped with a stirring rod, fill 4-chloroanisole (28.4mg, 0.20mmol, 1.0 equivalents), 44 (9.7mg, 0.01mmol, 5mol%) and rubidium carbonate (139mg, 0.6mmol, 3 equivalents), be placed under the positive pressure of argon, and under high vacuum, undergo three evacuation / backfill cycles. Then dioxane (2mL, 0.1M) and hydrazine monohydrate (50 μ L, 1mmol, 5 equivalents) are added to the reaction, and the reaction is heated at 120 ℃ for 12h. After the time indicated, acetylacetone (184 μ L, 1.8mmol, 9.0 equivalents) and the 2M TFA (0.4mL, 0.8mmol, 4 equivalents) in EtOH are added to the reaction. Then the reaction is heated at 100 ℃ for 6h under agitation. Then, the reaction mixture is diluted with CH cl (10mL), filtered, and concentrated. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product as a yellow oil. Yield 87% (35.2 mg). 1 H NMR (500MHz, CDCl3) δ7.32 (d, J = 8.9 Hz, 2H), 6.95 (d, J = 8.9 Hz, 2H), 5.96 (s, 1H), 3.84 (s, 3H), 2.29 (s, 3H), 2.24 (s, 3H). 13 C NMR (125MHz, CDCl3) δ158.90,148.63,139.60,133.21,126.50,114.23,106.36,55.66,13.64,12.28.

[0776] General Procedure for the Suzuki-Miyaura Cross-Coupling of Aryl Mesylates and Tosylates (General Procedure VI)

[0777]

[0778] An oven-dried vial equipped with a stir bar was charged with aryl methanesulfonate (neat, 1.0 equiv), boronic acid (typically, 4.5 equiv), potassium phosphate (typically, 3.0 equiv), Pd-NHC catalyst (typically, 5 mol%), placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Isopropyl alcohol (typically 0.25 M) was added with vigorous stirring and the reaction mixture was placed in an oil bath at 130° C. and stirred for the indicated time. After the indicated time, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), filtered, and concentrated. By 1Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion, selectivity, and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0779] Synthesis of 4-methoxy-4'-(trifluoromethyl)-1,1'-biphenyl (General Procedure VI)

[0780]

[0781] According to the general procedure, 4-methoxyphenyl methanesulfonate (0.20 mmol), 4-trifluoromethylphenylboronic acid (0.90 mmol), K3PO4 (0.60 mmol) and 43 (0.01 mmol) were reacted in isopropanol (0.25 M) at 130°C for 12 h to afford the title compound (50.3 mg) as a white solid in 99% yield after work-up and chromatography. 1 H NMR (500 MHz, CDCl3) 1 H NMR (500MHz, CDCl3) δ7.68-7.64 (m, 4H), 7.55 (d, J = 8.8Hz, 2H), 7.01 (d, J = 8.7Hz, 2H), 3.87 (s, 3H). 13 C NMR (125 MHz, CDCl3) δ 13 C NMR (125MHz, CDCl3) δ159.84, 144.29, 132.18, 128.69 (q, J = 32.4Hz), 128.35, 126.87, 125.67 (q, J = 3.8Hz), 124.38 (q, J = 271.8Hz), 55.39.

[0782] General Procedure for the Buchwald-Hartwig Amination of Aryl Mesylates and Tosylates (General Procedure VII)

[0783]

[0784] An oven-dried vial equipped with a stir bar was charged with aryl methanesulfonate (neat, 1.0 equiv), aniline (typically 1.2 equiv), potassium phosphate (typically 2.0 equiv), Pd-NHC catalyst (typically 5 mol%), placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Tert-amyl alcohol (typically 0.25 M) was added with vigorous stirring and the reaction mixture was placed in an oil bath at 120° C. and stirred for the indicated time. After the indicated time, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), filtered, and concentrated. By 1 Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion, selectivity, and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0785] Synthesis of N-(p-Tolyl)quinolin-6-amine (General Procedure VII)

[0786]

[0787] According to the general procedure, quinolin-6-yl methanesulfonate (0.20 mmol), p-toluidine (0.24 mmol), K 3 PO 4 (0.40 mmol) and 42 (0.01 mmol) were reacted in tert-amyl alcohol (0.25 M) at 130° C. for 12 h to afford the title compound (46.4 mg) as a brown oil in 99% yield after work-up and chromatography. 1 H NMR (500MHz, CDCl3) δ8.60(dd,J=4.3,1.7Hz,1H),7.88(d,J=9.0Hz,1H),7.82(dd,J=8.3,1.6Hz,1H),7.29(dd,J= 9.1, 2.6Hz, 1H), 7.20 (dd, J=8.3, 4.3Hz, 1H), 7.18 (t, J=2.4Hz, 1H), 7.10–7.02 (m, 4H), 5.89 (s, 1H), 2.27 (s, 3H). δ 13 C NMR (125MHz, CDCl3) δ147.25,144.07,142.53,139.31,134.28,132.27,130.49,130.06,129.70,122.68,121.47,120.20,108.14,20.82.

[0788] General Procedure for the Suzuki-Miyaura Cross-Coupling of Arylsulfamates (General Procedure VIII)

[0789]

[0790] An oven-dried vial equipped with a stir bar was charged with arylsulfamate (neat, 1.0 equiv), boronic acid (typically, 4.5 equiv), potassium phosphate (typically, 3.0 equiv), Pd-NHC catalyst (typically, 5 mol%), placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Isopropyl alcohol (typically 0.25 M) was added with vigorous stirring and the reaction mixture was placed in an oil bath at 130° C. and stirred for the indicated time. After the indicated time, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), filtered, and concentrated. By 1 Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion, selectivity, and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0791] Synthesis of 1-(4'-methoxy-[1,1'-biphenyl]-4-yl)ethan-1-one (General Procedure VIII)

[0792]

[0793] According to the general procedure, 4-methoxy-N,N-dimethylaminosulfonate (0.20 mmol), (4-acetylphenyl)boronic acid (0.90 mmol), K3PO4 (0.60 mmol) and 42 (0.01 mmol) were reacted in isopropanol (0.25 M) at 130 ° C. for 12 h to afford the title compound (41.7 mg) as a white solid in 92% yield after work-up and chromatography. 1 H NMR (500 MHz, CDCl3) 1 H NMR (500MHz, CDCl3) δ 8.01 (d, J = 8.5 Hz, 2H), 7.65 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.00 (d, J = 8.7 Hz, 2H), 3.87 (s, 3H), 2.63 (s, 3H). δ 13 C NMR (125MHz, CDCl3) δ197.73,159.92,145.38,135.30,132.27,128.95,128.38,126.63,114.41,55.40,26.64.55.39.

[0794] General Procedure for the Buchwald-Hartwig Amination of Arylsulfamates (General Procedure IX)

[0795]

[0796] An oven-dried vial equipped with a stir bar was charged with arylsulfamate (neat, 1.0 equiv), aniline (typically 1.2 equiv), potassium phosphate (typically 2.0 equiv), Pd-NHC catalyst (typically 5 mol%), placed under a positive pressure of argon and subjected to three evacuation / backfill cycles under high vacuum. Tert-amyl alcohol (typically 0.25 M) was added with vigorous stirring and the reaction mixture was placed in an oil bath at 130° C. and stirred for the indicated time. After the indicated time, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (10 mL), filtered, and concentrated. By 1 Samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using an internal standard and comparison with authentic samples to obtain conversion, selectivity, and yield. Purification by silica gel chromatography (EtOAc / hexanes) provided the title product.

[0797] Synthesis of N-(p-Tolyl)naphthalene-2-amine (General Procedure IX)

[0798]

[0799] According to the general procedure, naphthalen-2-yldimethylsulfamate (0.20 mmol), p-toluidine (0.24 mmol), K 3 PO 4 (0.40 mmol) and 42 (0.01 mmol) were reacted in tert-amyl alcohol (0.25 M) at 130° C. for 12 h to afford the title compound (46.0 mg) as a brown oil in 99% yield after work-up and chromatography. 1 H NMR (500MHz, CDCl3) δ7.63(d,J=8.8Hz,1H),7.53(d,J=8.2Hz,1H),7.34–7.26(m,1H),7.27(d,J=2.2Hz ,1H),7.19(t,J=7.5Hz,1H),7.09(dd,J=8.8,2.3Hz,1H),7.07–6.96(m,4H),5.68(s,1H),2.25(s,3H). δ 13 C NMR (125MHz, CDCl3) δ141.71,140.10,134.73,131.40,129.97,129.15,128.88,127.64,126.42,126.37,123.19,119.59,119.37,110.28,20.78.

[0800] General Procedure for the Hydroxylation of Aryl Chlorides: Synthesis of 3-Methoxyphenol (General Procedure X)

[0801]

[0802] In the oven-dried vial equipped with a stirring rod, 3-chloroanisole (28.4 mg, 0.20 mmol, 1.0 equivalent), 44 (9.7 mg, 0.01 mmol, 5 mol%) and cesium hydroxide monohydrate (67 mg, 0.4 mmol, 2 equivalents) were filled, placed under the positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Then dioxane (1 mL, 0.2 M) was added to the reaction, and the reaction was heated at 120 ° C for 16 h. After the indicated time, quenched with saturated 1 M HCl aqueous solution (2 mL) and extracted with ethyl acetate (2 × 5 mL). The organic layer merged was dried over anhydrous Na SO and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexane) provided the title product (24.3 mg) in a 98% yield. Yellow oil. Spectral data matched literature values.

[0803] General Procedure for the Amination of Aryl Methyl Sulfides: Synthesis of Diphenylamines (General Procedure XI)

[0804]

[0805] Thioanisole (25 mg, 0.2 mmol, 1.0 equivalent), aniline (37.2 mg, 0.4 mmol, 2 equivalents), 42 (6.6 mg, 0.01 mmol, 5 mol%) were loaded into an oven-dried vial equipped with a stirring rod, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Under vigorous stirring, at room temperature, toluene (1 mL, 0.2 M) and 1 M NaHMDS (0.4 mL, 0.4 mmol, 2 equivalents) in toluene were added, the reaction mixture was placed in a preheated oil bath and stirred at 100 ° C for 12 h. After 12 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2 × 5 mL). The combined organic layers were dried over anhydrous Na SO and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexane) provided the title product (31.8 mg) in a 94% yield. White solid. 1 H NMR (500MHz, CDCl3) δ7.26 (t, J = 7.7Hz, 4H), 7.07 (d, J = 8.5Hz, 4H), 6.92 (t, J = 7.3Hz, 2H), 5.78 (s, 1H). 13 C NMR (125MHz, CDCl3) δ143.22, 129.49, 121.19, 117.99.

[0806] General Procedure for the Amination of Aryl Sulfoxides: Synthesis of 4-Methyl-N-phenylaniline (General Procedure XII)

[0807]

[0808] In an oven-dried vial equipped with a stirring rod, diphenyl sulfoxide (61 mg, 0.3 mmol, 1.5 equivalents), p-toluidine (21.4 mg, 0.2 mmol, 1 equivalent), 42 (6.6 mg, 0.01 mmol, 5 mol%) were loaded, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Under vigorous stirring, at room temperature, THF (1 mL, 0.2 M) and 1 M LiHMDS (0.4 mL, 0.4 mmol, 2 equivalents) in THF were added, the reaction mixture was placed in a preheated oil bath and stirred at 80 ° C for 12 h. After 12 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2 × 5 mL). The combined organic layers were dried over anhydrous Na SO and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexane) provided the title product (33.7 mg) in a 92% yield. White solid. 1 H NMR (500MHz, CDCl3) δ7.25–7.19(m,2H),7.07(d,J=8.2Hz,2H),7.02–6.95(m,4H),6.86(t,J=7.3Hz,1H),5.64(s,1H),2.29(s,3H). 13 C NMR (125MHz, CDCl3) δ144.06,140.39,131.11,130.00,129.45,120.47,119.06,117.02,20.83.

[0809] General Procedure for Amination of Aryl Chlorides: Synthesis of 4-(p-Tolyl)morpholine (General Procedure XIII)

[0810]

[0811] 4-Chlorotoluene (25.3 mg, 0.2 mmol, 1.5 equivalents), morpholine (24.2 mg, 0.28 mmol, 1.4 equivalents), 42 (1.3 mg, 0.002 mmol, 1 mol%) and KOtBu (31.4 mg, 0.28 mmol, 1.4 equivalents) were loaded into an oven-dried vial equipped with a stirring rod, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Under vigorous stirring, at room temperature, CPME (1 mL, 0.2 M) was added, the reaction mixture was placed in a preheated oil bath and stirred at 60 ° C for 16 h. After 16 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2 × 5 mL). The combined organic layers were dried over anhydrous Na SO and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexane) provided the title product (35 mg) in a 99% yield. White solid. Spectral data matched literature values.

[0812] General Procedure for Amination of Aryl Chlorides: Synthesis of 4-Methyl-N-phenylaniline (General Procedure XIV)

[0813]

[0814] 4-Chlorotoluene (25.3 mg, 0.2 mmol, 1.5 equiv), aniline (26 mg, 0.28 mmol, 1.4 equiv), 42 (1.3 mg, 0.002 mmol, 1 mol%) and NaOtBu (26.9 mg, 0.28 mmol, 1.4 equiv) were charged into an oven-dried vial equipped with a stir bar, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, THF (1 mL, 0.2 M) was added at room temperature, the reaction mixture was placed in a preheated oil bath and stirred at 60° C. for 16 h. After 16 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography (EtOAc / hexane) provided the title product (36.3 mg) in a 99% yield. White solid. 1 H NMR (500MHz, CDCl3) δ7.25–7.19(m,2H),7.07(d,J=8.2Hz,2H),7.02–6.95(m,4H),6.86(t,J=7.3Hz,1H),5.64(s,1H),2.29(s,3H). 13C NMR (125MHz, CDCl3) δ144.06,140.39,131.11,130.00,129.45,120.47,119.06,117.02,20.83.

[0815] General Procedure for the Suzuki-Miyaura Cross-Coupling of Aryl Chlorides: Synthesis of 4-Methoxy-1,1'-Biphenyl (General Procedure XV)

[0816]

[0817] 4-Chloroanisole (28.5 mg, 0.2 mmol, 1.5 equivalents), phenylboronic acid (36.6 mg, 0.3 mmol, 1.5 equivalents), 42 (1.3 mg, 0.002 mmol, 1 mol%) and KOtBu (33.6 mg, 0.3 mmol, 1.5 equivalents) were loaded into an oven-dried vial equipped with a stirring bar, placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. Under vigorous stirring, at room temperature, nBuOH (1 mL, 0.2 M) was added, the reaction mixture was placed in a preheated oil bath and stirred at 60 ° C for 16 h. After 16 h, the reaction mixture was diluted with CH2Cl2 (10 mL), filtered, and concentrated. The title product was provided as a white solid by purification by silica gel chromatography (EtOAc / hexane). Yield 93% (34.2 mg). 1 H NMR (500MHz, CDCl3) δ7.59-7.52 (m, 4H), 7.43 (t, J = 7.8Hz, 2H), 7.31 (t, J = 7.4Hz, 1H), 6.99 (d, J = 8.8Hz, 2H), 3.86 (s, 3H). 13 C NMR (125MHz, CDCl3) δ159.28, 140.97, 133.92, 128.86, 128.29, 126.88, 126.79, 114.34, 55.49.

[0818] General Procedure for the Amination of Aryl Fluorides (Ar-F) (General Procedure XVI)

[0819]

[0820] An oven-dried vial equipped with a stir bar was charged with aryl fluoride (neat, 1.0 equiv), aniline (typically 1.5 equiv), [Pd(ligand)Cl]2 (typically 2.5 mol%) and NHC·HCl (10 mol% or 20 mol%), placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, toluene (typically 0.2 M) and LiHMDS in toluene (1 M solution, 2 equiv) were added at room temperature, and the reaction mixture was placed in a preheated oil bath (typically 130°C) and stirred for 16 h. After 16 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2×5 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. 1 H NMR (CDCl3, 500 MHz) and GC-MS were used to analyze the samples using internal standards and comparison with authentic samples to obtain conversion and yield. The title product was purified by silica gel chromatography. In certain embodiments, the "ligand" is cinnamyl. In certain embodiments, NHC is 5-(2,4,6-phenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride. In certain embodiments, [Pd(ligand)Cl]2 and NHC·HCl react to form compound 74 in situ.

[0821] Synthesis of 4-methoxy-N-phenylaniline (General Procedure XVI)

[0822]

[0823] An oven-dried vial equipped with a stir bar was charged with 4-fluoroanisole (25.2 mg, 0.2 mmol, 1.0 equiv), aniline (28 mg, 0.3 mmol, 1.5 equiv), [Pd(cin)Cl]2 (2.6 mg, 0.0025 mmol, 2.5 mol%) and 5-(2,4,6-phenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride (9.5 mg, 0.01 mmol, 10 mol%), placed under a positive pressure of argon, and subjected to three evacuation / backfill cycles under high vacuum. With vigorous stirring, toluene (1 mL, 0.2 M) and LiHMDS in toluene (1 M, 0.4 mL, 0.4 mmol, 2 equiv) were added at room temperature, and the reaction mixture was placed in a preheated oil bath (130°C) and stirred for 16 h. After 16 h, the reaction mixture was cooled to room temperature, quenched with saturated ammonium chloride solution (5 mL) and extracted with ethyl acetate (2 × 5 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by silica gel chromatography provided 4-methoxy-N-phenylaniline as a brown solid. Yield 90% (35.8 mg). 1 H NMR (500MHz, CDCl3) δ7.22(t,J=7.5Hz,2H),7.08(d,J=8.9Hz,2H),6.92(d,J=7. 6Hz, 2H), 6.87 (d, J = 8.9Hz, 2H), 6.84 (t, J = 7.4Hz, 1H), 5.50 (s, 1H), 3.81 (s, 3H). 13 C NMR (126MHz, CDCl3) δ155.42, 145.31, 135.86, 129.44, 122.35, 119.70, 115.78, 114.81, 55.72.

[0824] General Procedure for the Reductive Amination of Alkynes with Nitroarenes (General Procedure XVII)

[0825]

[0826] An oven-dried vial equipped with a stir bar was charged with alkyne (neat if solid, 1.0 equiv), nitroarene (typically, 2.0 equiv), [(NHC)AuCl] (typically, 5 mol%), Lewis acid (10 mol%), and Molecular sieves (MS) (typically 100 mg). Toluene or trifluorotoluene (typically 0.25 M), phenylsilane (typically 10 equiv.) and alkyne (pure if liquid, 1.0 equiv.) are added with vigorous stirring. Water (typically 5 equiv.) is added if necessary, and the reaction mixture is placed in a preheated oil bath (typically 40° C.) and stirred for 16 h. After 16 h, the reaction mixture is cooled to room temperature, diluted with CH2Cl2 (10 mL), filtered, and concentrated. 1 The samples were analyzed by H NMR (CDCl3, 500 MHz) and GC-MS using internal standards and comparison with authentic samples to obtain conversion and yield. Purification by silica gel chromatography provided the title product. In certain embodiments, (NHC)AuX is compound 52. In certain embodiments, the Lewis acid is [Ag(MeCN)2] + BARF - .

[0827] Synthesis of 4-methoxy-N-(1-phenylethyl)aniline (General Procedure XVII)

[0828]

[0829] An oven-dried vial equipped with a stir bar was charged with 4-nitroanisole (61.2 mg, 0.4 mmol, 2.0 equiv), (52)[(5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride] (6.3 mg, 0.01 mg, 5 mol%), [Ag(MeCN)2] + BARF – (21 mg, 0.02 mmol, 10 mol%) and Molecular sieves (MS) (100 mg). Toluene (0.8 mL, 0.25 M), phenylsilane (216 mg, 0.2 mmol, 10 equivalents) and phenylacetylene (20.4 mg, 0.2 mmol, 1.0 equivalents) were added under vigorous stirring. The reaction mixture was placed in a preheated oil bath (40 ° C) and stirred for 16 h. After 16 h, the reaction mixture was cooled to room temperature, diluted with CH2Cl2 (10 mL), filtered, and concentrated. Purification by silica gel chromatography provided 4-methoxy-N-(1-phenylethyl)aniline as a colorless oil. Yield 91% (41.4 mg).

[0830] Example 5: Characterization of NHC ligands and ligand-metal complexes

[0831] Electronic characterization

[0832] NHC-Se (5 complexes) and NHC-Rh(I) complexes (3 complexes) were synthesized for the characterization purpose of p-acceptance and s-donation. 119.35 ppm of (71)(CDCl3), 118.02 ppm of (72), 170.40 ppm of (73), 143.44 ppm of (70), and 100.66 ppm of (69) were obtained. Se Value and IPr(d Se =90ppm), IPr*(d Se =106ppm) and IMes(d Se =27ppm), indicating that this type of ligand has stronger p-accepting properties. CO =2031.6cm -1 (2045.3cm -1 TEP), for (64) average n CO =2032.2cm -1 (2045.8cm -1 TEP) and for (66) average n Co =2031.2cm -1 (2045.0cm -1 The TEP of the ligand provides a combined measure of the electronic properties of the ligand and can be compared with IPr (2051.5 cm -1 TEP), IPr*(2052.7cm -1 TEP) and IMe S (2050.8cm -1 This indicates the strong σ-donation of this type of ligand. 1 H NMR spectrum (NHC salt) 13 The single-bond C—H J coupling constant of the C satellite provides a good indication of the σ-donating properties of the NHC ligand. The value of 225 Hz for the ImPy-Dipp-IMes L-type ligand (CDCl3) is consistent with the strong σ-donating properties of this ligand (see, IPr: 1 J CH =223.7Hz).

[0833] Complexation studies

[0834] Complexation studies demonstrate that the ligands of the present disclosure can be readily used to synthesize well-defined, moisture- and air-stable complexes with Pd(II), Au(I), Ag(I), Cu(I), Rh(I), and Se. All prepared complexes were found to be air- and moisture-stable in the solid state, allowing for their application in catalysis.

[0835] X-ray structural analysis

[0836] The structures of eight Pd(II) complexes, six Au(I) complexes, and representative Cu(I) and Rh(I) complexes have been fully characterized by X-ray crystallographic analysis (Table 2 and Figure 7A-7B 、 Figure 8A-8B as well as Figure 9A-9B ).

[0837] Table 2. Buried volume (V) of selected compounds bur %)

[0838] Compound Metal <![CDATA[V bur %]]> <![CDATA[51 a ]]> Au 46.4％ <![CDATA[52 a ]]> Au 49.5％ <![CDATA[53 a ]]> Au 59.6％ <![CDATA[54 a ]]> Au 68.7％ <![CDATA[56 a ]]> Au 52.6％ <![CDATA[[Au(34)Cl] a ]]> Au 50.9％ <![CDATA[37 b ]]> Pd 42.0％ <![CDATA[39 b ]]> Pd 43.2％ <![CDATA[41 b ]]> Pd 42.1％ <![CDATA[43 b ]]> Pd 45.6％ 38c Pd 41.7％ <![CDATA[40 d ]]> Pd 40.9％ <![CDATA[47 e ]]> Pd 43.8％ <![CDATA[49 f ]]> Pd 39.0％ <![CDATA[59 g ]]> Cu 62.0％ <![CDATA[64 h ]]> Rh 42.0％

[0839] a [Au(NHC)Cl]; b [Pd(NHC)(cin)Cl]; c [Pd(NHC)(allyl)Cl]; d [Pd(NHC)(1-t-Bu-ind)Cl]; e [Pd(NHC)(3-Cl-py)Cl2]; f [Pd(NHC)(C6H4-CH2NMe2)Cl]; g [Cu(NHC)Cl]; h [Rh(NHC)(CO)2Cl].

[0840] Structural characterization

[0841] The buried volume % (V bur %) is 50.9%, which is comparable to the 51.9% (V bur %) and 52.6% (V bur %). These values ​​define an ideal catalytic pocket to accommodate substrates for Pd-catalyzed cross-coupling of this class of biaryl L-type ligands with commonly used substrates. In comparison, the 54.1% (V bur %) and 46.4% (V bur %) are too large and too small, respectively, for efficient catalysis in Pd-catalyzed cross-couplings of common substrates.

[0842] In addition, for 52, 49.5% of (V bur %) is within the expected range for opening the catalytic pocket by removing the 4-substitution while maintaining the 2,6-di-ortho substitution of the biaryl ring (cf. [Au(35)Cl], 51.9%). Finally, 59.6% (V bur %) and 58.7% (V bur%) indicates a bulky but flexible biaryl L-type ligand and can be combined with the 50.4% (V bur The spatial extent of this catalytic pocket is ideal for Pd-catalyzed cross-coupling of small nucleophiles, where the flexibility of the bis-diphenylmethyl motif provides a selective steric environment for the catalytic pocket.

[0843] The linear metal-NHC complexes of the spatially confined biaryl L-type NHC ligands and their square planar complexes in the same series of ligands (V bur %) can show that these ligands can adapt to the space environment. For example, using (34) as a representative ligand, from [Pd(34)(1-t-Bu-ind)Cl] to [Au(34)Cl] complex, (V bur %) changes from 40.9% to 50.9% (25% of D). In addition, even in square planar Pd(II) complexes with different ligands on Pd, there is spatial differentiation, corresponding to (V bur %) decreases with increasing ligand space demand, [Pd(34)(1-t-Bu-ind)Cl](V bur %=40.9%)<[Pd(34)(allyl)Cl](V bur %=41.7%)<[Pd(34)(cin)Cl](V bur %=43.2%)<[Pd(34)(3-Cl-py)Cl2](V bur %=43.8%).

[0844] Finally, the space-demanding bulky but flexible (59) buried volume % (V bur The rigid spatial arrangement of the biaryl motif, combined with the adaptability and flexibility of the C5 / N2 substituents to the steric environment, provides a unique steric environment for catalysis that is unavailable in other classes of NHC ligands developed to date.

[0845] DFT analysis

[0846] To gain insight into the spatial and electronic structures of the spatially confined L-type ligands, calculations at the B3LYP 6-311++g(d,p) level of theory ( Figures 10A-10F ).

[0847] Spatial Effect

[0848] To evaluate the steric effect, the geometry and buried volume percentage (V bur%). The buried volume % (V bur %) in the series of ligands 33, 34, and 17, respectively, and in the series of ligands 35, 36, and 19, respectively, 49.8%, 52.4%, 54.2%. The steric requirements of the N2 wing tip substituent vary with the steric requirements of the C5 substituent, and there is an excellent linear correlation between the two (R 2 =0.99).

[0849] The steric match between the C5 and N2 substituents supports the findings of X-ray crystallography. The biaryl L-type ligands with C5 / N2 Dipp / IMes combinations are sterically similar (V bur % = 49.8% - 50.1%), whose catalytic pocket accommodates substrates for Pd-catalyzed cross-coupling. Substitution of C5 / N2 with more sterically demanding substituents results in a reduction in the catalytic pocket size (V bur % = 51.8% - 54.2%), while the substitution of C5 / N2 with less sterically demanding substituents results in a low buried volume % (V bur % = 46.8%). For each quadrant, the quadrant distribution for 34 is 55.3%, 55.3%, 45.0%, 45.0%, and for 35 is 60.9%, 61.4%, 38.5%, 38.2%.

[0850] The buried volume % values ​​can be compared with the 36.4%, 42.6% and 49.7% (V) values ​​of the reference imidazolylidenes [Cu(IMes)Cl], [Cu(IPr)Cl] and [Cu(IPr*)Cl] determined at the same theoretical level. bur %)compared to.

[0851] Electronic properties

[0852] To evaluate the electronic properties of the spatially confined L-type ligands, the HOMO and LUMO energy levels were determined at the B3LYP 6-311++g(d,p) level of theory ( Figures 11A-11CThe HOMO-1 (s-bonding orbital) is -5.86 eV, -5.91 eV, -5.96 eV in the series of 51, 34, and 17, and -5.87 eV, -5.91 eV, -5.95 eV in the series of 35, 36, and 19, which are in the same range as those of the standard imidazolyl ligands IMes (-5.90 eV), IPr (-6.01 eV), and IPr* (-6.12 eV) determined at the same level of theory. In addition, the LUMO (p-accepting orbital) is -1.24 eV, -1.29 eV, -1.25 eV in the series of 33, 34 and 17, and -1.25 eV, -1.30 eV, -1.25 eV in the series of 35, 36 and 19, which are much lower than those of the standard imidazolyl ligands IMes (-0.33 eV), IPr (-0.48 eV), IPr* (-0.90 eV) determined at the same theoretical level.

[0853] In addition, the HOMO (p-donating orbital) is -5.43 eV, -5.49 eV, -5.42 eV in the series of 33, 34 and 17 and -5.44 eV, -5.50 eV, -5.40 eV in the series of 35, 36 and 19, which are much higher than the p-donating orbitals of the standard imidazolyl ligands IMes (-6.44 eV), IPr (-6.55 eV), IPr* (-6.28 eV) determined at the same theoretical level.

[0854] This demonstrates that: (1) the sterically confined L-type ligands are strong nucleophiles, as expected for sterically bulky N-Ar NHC ligands, with σ-donations matching those of IPr and IMes and significantly stronger than those of phosphines (e.g., dialkylbiarylphosphines), and (2) they are significantly better π-acceptors than standard imidazolylidene IPr and IMes ligands. Furthermore, the biaryl L-type ligands are characterized by strong p-donation capabilities that are not available in standard imidazolylidene IPr and IMes ligands.

[0855] catalytic

[0856] Catalytic studies were conducted to evaluate the activity of the ligands of the present disclosure and / or their catalyst complexes. These ligands were designed from the outset to utilize a pivotal biaryl arrangement that stabilizes the reactive ligand-metal intermediate via rigid, spatially confined, five-membered interactions in palladium cross-coupling catalysis. Palladium-catalyzed cross-coupling reactions represent an important application of ligands in contemporary transition metal catalysis, which has fundamental and practical significance in medicinal chemistry, drug discovery, biochemistry, agricultural chemistry, natural product synthesis, small molecule synthesis, and polymer synthesis.

[0857] In particular, the activation of non-reactive bonds such as CN, CS, and CO is targeted, which is one of the most underexplored areas in cross-coupling chemistry. Activation of stronger CX bonds (X = N, S, O) requires strong σ-donating ligands to promote oxidative addition, while the stabilizing interaction between the idio position of the biaryl ring and palladium further reduces the barrier to oxidative addition. The end result is the cross-coupling of normally non-reactive CX bonds, which has many synthetic advantages: (1) it displays orthogonal reactivity with classic aryl halides and pseudohalides, (2) it provides a synthetic handle in molecular functionalization, (3) it can be applied to highly desirable late-stage functionalizations, and (4) it is derived from a different precursor library than aryl halides and pseudohalides.

[0858] The following non-limiting reactions have been demonstrated using the sterically confined biaryl L-type ligands of the present disclosure:

[0859] (a) Suzuki-Miyaura cross-coupling of nitroarenes (Ar-NO2) using a well-defined air- and moisture-stable [Pd(NHC)(cin)Cl] precatalyst ( Figures 12A-12B ).

[0860] (b) Suzuki-Miyaura cross-coupling of nitroarenes (Ar-NO2) using a well-defined air- and moisture-stable [Pd–PEPPSI] precatalyst ( Figures 13A-13B ).

[0861] (c) Buchwald-Hartwig amination of alkyl sulfoxides (Ar-S(O)R, R = alkyl) Figures 14A-14E ). *This reaction requires a sterically constrained L-type ligand. Classical NHCs showed negligible reactivity (<20%). Phosphine ligands showed negligible reactivity.

[0862] (d) Buchwald-Hartwig amination of thiophenol (Ar-SH) Figures 15A-15C ). The spatially confined L-type ligands showed higher reactivity than the classical NHC. Without wishing to be bound by theory, the difference in reactivity may be due to the steric tuning of the catalytic pocket that is not possible for imidazolylidenes and related ligands. The phosphine ligands showed negligible reactivity.

[0863] (e) Monoarylation of the parent hydrazine with an aryl chloride (Ar-Cl) Figures 16A-16D). *This reaction requires a sterically defined L-type ligand. Classical NHCs showed negligible reactivity (<20%). Phosphine ligands showed limited reactivity. Aryl bromides (Ar-Br) are also effective substrates. NHC=ImPy-Trip-IPr* is the ligand of choice, as a well-defined [Pd(NHC)(cin)Cl] complex. Since the reaction requires a weak base to achieve broad functional group tolerance, without wishing to be bound by theory, the reaction may be ideal for a well-defined Pd-NHC catalyst (i.e., in situ preparation is ineffective).

[0864] (f) Suzuki-Miyaura cross-coupling of aryl methanesulfonates and aryl toluenesulfonates (Ar-OR, R = methanesulfonyloxy or 4-toluenesulfonyloxy) Figures 17A-17C ). Spatially confined L-type ligands showed higher reactivity than classical NHCs. IPr* was the only comparable, but less reactive NHC ligand, which, without wishing to be bound by theory, could indicate that the high reactivity of L-type biaryl ligands is due to steric tuning of the catalytic pocket. In situ prepared catalysts (Pd(acac)2 / K3PO4 or Pd2(dba)3 / K3PO4) were also effective but less reactive. The described method represents the first universal Suzuki-Miyaura cross-coupling of aryl mesylates / aryl toluenesulfonates catalyzed by a Pd-NHC system.

[0865] (g) Buchwald-Hartwig amination of aryl methanesulfonates and aryl sulfonates (Ar-OR, R = methanesulfonyloxy or 4-toluenesulfonyloxy) Figures 18A-18B ). This reaction requires a spatially confined L-type ligand. Alternative NHCs showed negligible reactivity (<10%). In situ prepared catalysts (Pd(acac)2 / K3PO4 or Pd2(dba)3 / K3PO4) were also effective but less reactive. This method represents the first universal Buchwald-Hartwig amination of aryl methanesulfonates catalyzed by a Pd-NHC system.

[0866] (h) Suzuki-Miyaura cross-coupling of arylsulfamate (Ar-OR, R=SO2NR2') Figures 19A-19B ). The reaction requires a sterically confined L-type ligand. Alternative NHCs showed negligible reactivity (<10%). IPr* was the only comparable, but much less reactive NHC ligand (50%), which could indicate that the high reactivity of the L-type biaryl ligand is due to steric tuning of the catalytic pocket. In situ prepared catalysts (Pd(acac)2 / K3PO4 or Pd2(dba)3 / K3PO4) were also effective but less reactive. The described method represents the first Suzuki-Miyaura cross-coupling of arylsulfamates catalyzed by a Pd-NHC system.

[0867] (i) Buchwald-Hartwig amination of arylsulfamates (Ar-OR, R=SO2NR2') Figure 20A-Figure 20B ). This reaction requires a spatially confined L-type ligand. Classical NHC shows negligible reactivity (<20%). In situ prepared catalysts (Pd(acac)2 / K3PO4 or Pd2(dba)3 / K3PO4) are also effective, but less reactive. This method represents the first Buchwald-Hartwig amination of arylsulfamates catalyzed by a Pd-NHC system.

[0868] Additionally, feasibility studies have been conducted that further demonstrate the utility of the catalyst complexes described herein:

[0869] (a) Hydroxylation of aryl chlorides (Ar-Cl). This reaction requires the sterically confined L-type ligands of the present disclosure. Alternative NHCs showed negligible reactivity (<5%) ( Figure 21A ).

[0870] (b) Buchwald-Hartwig amination of aryl methyl sulfide (Ar-SMe) Figure 21B ).

[0871] (c) Buchwald-Hartwig amination of aryl sulfoxides (Ar-S(O)R, R = aryl) Figure 21C ).

[0872] (d) A comparative study of the Buchwald-Hartwig amination of aryl chlorides (Ar-Cl) has been conducted. The spatially confined L-type ligands of the present disclosure show improved reactivity compared to the standard [Pd(IPr)(cin)Cl] (Neolyst CX31, CAS: 884879-23-6). (Conditions: KOt-Bu, CPME, 60°C; NaOt-Bu, THF, 60°C) Figure 21D ).

[0873] (e) A comparative study of the Suzuki-Miyaura cross-coupling of aryl chlorides (Ar-Cl) has been performed. The spatially confined L-type ligand showed comparable reactivity to the standard [Pd(IPr)(cin)Cl] (Neolyst CX31, CAS: 884879-23-6). (Conditions: KOt-Bu, n-BuOH, 60°C; K3PO4, 2-MeTHF, 60°C) Figure 21E ).

[0874] (f) Suzuki-Miyaura cross-coupling of aryl pivalates (Ar-OR, R=COt-Bu). This reaction requires the sterically constrained L-type ligands of the present disclosure. Classical NHC showed negligible reactivity (<5%). This method represents the first activation of O-acylated phenols by Pd catalysis.

[0875] Listed implementation plans

[0876] The following exemplary embodiments are provided, and their numbering should not be construed as designating a level of importance:

[0877] Embodiment 1 provides a compound of formula (I):

[0878]

[0879] in:

[0880] T 1 Is N or CR 1a ;

[0881] T 2 Is N or CR 1b ;

[0882] T 3 Is N or CR 1c ;

[0883] R 1a 、R 1b and R 1c Each is independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0884] where R 1a 、R 1b and R 1c Each optional substituent in each of is independently selected from halogen,

[0885] C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group,

[0886] Among them, R 1a 、R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 Heterocyclic group

[0887] or optionally substituted C6-C 10 aryl;

[0888] R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 heterocyclic group;

[0889] R 3 Selected from optionally substituted C6-C 10 aryl, optionally substituted C2-C8 heteroaryl and optionally substituted C3-C8 cycloalkyl,

[0890] where R 3 Each optional substituent is independently selected from at least one of the following: H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、

[0891] N(R A )(R B ), C(=O)R A 、C(=O)N(R A )(R B ), C(=O)OR B 、N(R A )S(=O)2R B 、

[0892] S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C 12 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl,

[0893] wherein the C1-C6 alkyl, C3-C8 cycloalkyl, C2-C12 Heterocyclyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl are each optionally substituted with at least one substituent selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0894] R 4 Selected from optionally substituted C3-C 12 Cycloalkyl and phenyl substituted by at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, phenyl and N(R A )(R B ),

[0895] wherein the C3-C 12 Each optional substituent in the cycloalkyl group is at least one selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclic group;

[0896] X is the counter anion;

[0897] R A and R B Each independently selected from H, C1-C6 alkyl, C1-C3 haloalkyl, C2-C6 alkenyl, benzyl, naphthyl, C4-C 10 Heteroaryl and phenyl, where R A and R B Each substituent in is optionally substituted with at least one substituent selected from the group consisting of CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, and halogen;

[0898] If T 1 It is CH, T 2 It is CH, T 3 is CH, and R 2 is H, then each of the following applies:

[0899] (a) If R 4 is 2,4,6-triisopropylphenyl, then R 3 Not 2,6-diisopropylphenyl, 2,4,6-trimethylphenyl, 2-methylphenyl, or 2,6-diethyl-4-methylphenyl;

[0900] (b) If R 4is 2,4,6-trimethylphenyl, then R 3 Not 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, adamantyl, 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl, or (2-(2-methoxyethoxy)ethoxy)phenyl;

[0901] (c) If R 4 is 2-methylphenyl, then R 3 Not 2,6-diisopropylphenyl;

[0902] (d) If R 4 is 4-tert-butyl-2-pyridyl, then R 3 is not 2,6-diisopropylphenyl; and

[0903] (e) If R 4 is 5-tetrahydroisoquinolinyl, then R 3 Not 2,6-diisopropylphenyl.

[0904] Embodiment 2 provides a compound according to embodiment 1, wherein at least one of the following applies:

[0905] (a)T 1 It's CR 1a ;

[0906] (b)T 2 It's CR 1b ;as well as

[0907] (c)T 3 It's CR 1c .

[0908] Embodiment 3 provides a compound according to embodiment 1 or 2, wherein at least one of the following applies:

[0909] (a)R 1a 、R 1b and R 1c At least one of them is H;

[0910] (b)R 1a 、R 1b and R 1c At least two of are H; and

[0911] (c)R 1a 、R 1b and R 1c Each of them is H.

[0912] Embodiment 4 provides a compound according to any one of embodiments 1-3, wherein R 2 It’s H.

[0913] Embodiment 5 provides a compound according to any one of embodiments 1-4, wherein R 3 yes:

[0914]

[0915] in:

[0916] R 3a 、R 3b 、R 3c 、R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0917] where R 3a 、R 3b 、R 3c 、R 3d and R 3e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

[0918] Embodiment 6 provides a compound according to embodiment 5, wherein R 3a 、R 3b 、R 3c 、R 3d and R 3e Each is independently selected from H, methyl, isopropyl, diphenylmethyl, methoxy and fluorine.

[0919] Embodiment 7 provides a compound according to embodiment 5 or 6, wherein one of the following applies:

[0920] (a)R 3b and R 3d are each independently H; or

[0921] (b)R 3b 、R 3c and R 3d Each independently is H.

[0922] Embodiment 8 provides a compound according to any one of embodiments 5-7, wherein one of the following applies:

[0923] (a)R 3a and R 3e are the same; or

[0924] (b)R 3a、R 3c and R 3e are the same.

[0925] Embodiment 9 provides a compound according to any one of embodiments 5-8, wherein one of the following applies:

[0926] (a)R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b 、R 3c and R 3d It is H;

[0927] (b)R 3a 、R 3c and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b and R 3d is H; or

[0928] (c)R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, R 3c is selected from halogen and C1-C6 alkoxy, and R 3b and R 3d It’s H.

[0929] Embodiment 10 provides a compound according to any one of embodiments 1-9, wherein R 3 Selected from:

[0930] Embodiment 11 provides a compound according to any one of embodiments 1-4, wherein R 3 It is cyclohexyl.

[0931] Embodiment 12 provides a compound according to any one of embodiments 1-11, wherein R 4 yes:

[0932]

[0933] in:

[0934] R 4a 、R 4b 、R 4c 、R 4d and R 4e are each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy,

[0935] where R4a 、R 4b 、R 4c 、R 4d and R 4e Each optional substituent in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

[0936] Embodiment 13 provides a compound according to embodiment 12, wherein R 4a 、R 4b 、R 4c 、R 4d and R 4e Each is independently selected from H, methyl, ethyl, isopropyl, cyclohexyl, tert-butyl, methoxy, isopropoxy, phenyl and dimethylamino.

[0937] Embodiment 14 provides a compound according to embodiment 12 or 13, wherein one of the following applies:

[0938] (a)R 4b 、R 4c 、R 4d and R 4e Each independently is H;

[0939] (b)R 4b 、R 4c and R 4d Each independently is H;

[0940] (c)R 4a 、R 4c and R 4e are each independently H; or

[0941] (d)R 4a 、R 4b 、R 4c 、R 4d and R 4e Neither is H.

[0942] Embodiment 15 provides a compound according to any one of embodiments 12-14, wherein one of the following applies:

[0943] (a)R 4a and R 4e are the same;

[0944] (b)R 4b and R 4d are the same;

[0945] (c)R4a 、R 4c and R 4e are the same;

[0946] (c)R 4a 、R 4b 、R 4c 、R 4d and R 4e are the same.

[0947] Embodiment 16 provides a compound according to any one of embodiments 12-15, wherein one of the following applies:

[0948] (a)R 4a is selected from C1-C6 alkyl and N(C1-C6 alkyl)2, and R 4b 、R 4c 、R 4d and R 4e Each independently is H;

[0949] (b)R 4a and R 4e are each independently C1-C6 alkyl, and R 4b 、R 4c and R 4d Each independently is H;

[0950] (c)R 4a and R 4e are each independently a C1-C6 alkoxy group, and R 4b 、R 4c and R 4d Each independently is H;

[0951] (d)R 4b and R 4d are each independently C1-C6 alkyl or phenyl, and R 4a 、R 4c and R 4e Each independently is H;

[0952] (e)R 4a 、R 4c and R 4e are each independently C1-C6 alkyl or C3-C8 cycloalkyl, and R 4b and R 4d Each independently is H;

[0953] (f)R 4a 、R 4c and R 4e are each independently a C1-C6 alkoxy group, and R 4b and R 4d are each independently H; or

[0954] (g)R 4a 、R 4b 、R 4c 、R 4d and R 4e Each is independently a C1-C6 alkyl group.

[0955] Embodiment 17 provides a compound according to any one of embodiments 1-16, wherein R 4 Selected from:

[0956]

[0957]

[0958] Embodiment 18 provides a compound according to any one of embodiments 1-11, wherein R 4 It is cyclohexyl or adamantyl.

[0959] Embodiment 19 provides a compound according to any one of...

Claims

1. A compound of formula (I): in: T 1 Is N or CR 1a ; T 2 Is N or CR 1b ; T 3 Is N or CR 1c ; R 1a , R 1b and R 1c Each is independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、N(R A )(R B )、C(=O)R A 、C(=O)N(R A )(R B )、C(=O)OR B 、N(R A )S(=O)2R B 、S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl, Where R 1a , R 1b and R 1c Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group, Among them, R 1a , R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 heterocyclic or optionally substituted C6-C 10 Aryl; R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 Heterocyclic group; R 3 is selected from optionally substituted C6-C 10 aryl, optionally substituted C2-C8 heteroaryl and optionally substituted C3-C8 cycloalkyl, Where R 3 Each optional substituent in is independently selected from at least one of the following: H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A , N(R A )(R B )、C(=O)R A 、C(=O)N(R A )(R B )、C(=O)OR B 、N(R A )S(=O)2R B 、 S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C 12 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl, wherein the C1-C6 alkyl, C3-C8 cycloalkyl, C2-C 12 The heterocyclyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl groups are each optionally substituted with at least one substituent selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl groups, and C2-C 12 Heterocyclic group; R 4 is selected from optionally substituted C3-C 12 Cycloalkyl and phenyl substituted by at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, phenyl and N(R A )(R B ), Wherein the C3-C 12 Each optional substituent in the cycloalkyl group is at least one selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group; X is a counter anion; R A and R B Each is independently selected from H, C1-C6 alkyl, C1-C3 haloalkyl, C2-C6 alkenyl, benzyl, naphthyl, C4-C 10 Heteroaryl and phenyl, where R A and R B Each substituent in is optionally substituted with at least one substituent selected from the group consisting of CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl and halogen; If T 1 It is CH, T 2 It is CH, T 3 is CH, and R 2 is H, then each of the following applies: (a) If R 4 is 2,4,6-triisopropylphenyl, then R 3 Not 2,6-diisopropylphenyl, 2,4,6-trimethylphenyl, 2-methylphenyl or 2,6-diethyl-4-methylphenyl; (b) If R 4 is 2,4,6-trimethylphenyl, then R 3 Not 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, adamantyl, 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl or (2-(2-methoxyethoxy)ethoxy)phenyl; (c) If R 4 is 2-methylphenyl, then R 3 Not 2,6-diisopropylphenyl; (d) If R 4 is 4-tert-butyl-2-pyridyl, then R 3 is not 2,6-diisopropylphenyl; and (e) If R 4 is 5-tetrahydroisoquinolinyl, then R 3 Not 2,6-diisopropylphenyl.

2. The compound according to claim 1, wherein at least one of the following applies: (a)T 1 Yes CR 1a ; (b)T 2 Yes CR 1b ;as well as (c)T 3 Yes CR 1c .

3. The compound according to claim 1 or 2, wherein at least one of the following applies: (a)R 1a , R 1b and R 1c At least one of them is H; (b)R 1a , R 1b and R 1c At least two of are H; and (c)R 1a , R 1b and R 1c Each of them is H.

4. A compound according to any one of claims 1 to 3, wherein R 2 It's H.

5. The compound according to any one of claims 1 to 4, wherein R 3 yes: in: R 3a , R 3b , R 3c , R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy, Where R 3a , R 3b , R 3c , R 3d and R 3e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

6. The compound according to claim 5, wherein R 3a , R 3b , R 3c , R 3d and R 3e Each is independently selected from H, methyl, isopropyl, diphenylmethyl, methoxy and fluorine.

7. The compound according to claim 5 or 6, wherein one of the following is applicable: (a)R 3b and R 3d are each independently H; or (b)R 3b , R 3c and R 3d Each independently is H.

8. A compound according to any one of claims 5-7, wherein one of the following applies: (a)R 3a and R 3e are the same; or (b)R 3a , R 3c and R 3e are the same.

9. A compound according to any one of claims 5 to 8, wherein one of the following applies: (a)R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b , R 3c and R 3d It is H; (b)R 3a , R 3c and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b and R 3dis H; or (c)R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, R 3c is selected from halogen and C1-C6 alkoxy, and R 3b and R 3d It's H.

10. A compound according to any one of claims 1 to 9, wherein R 3 Selected from:

11. A compound according to any one of claims 1 to 4, wherein R 3 It is cyclohexyl.

12. A compound according to any one of claims 1 to 11, wherein R 4 yes: in: R 4a , R 4b , R 4c , R 4d and R 4e each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy, Where R 4a , R 4b , R 4c , R 4d and R 4e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

13. The compound according to claim 12, wherein R 4a , R 4b , R 4c , R 4d and R 4e Each is independently selected from H, methyl, ethyl, isopropyl, cyclohexyl, tert-butyl, methoxy, isopropoxy, phenyl and dimethylamino.

14. A compound according to claim 12 or 13, wherein one of the following applies: (a)R 4b , R 4c , R 4d and R 4e Each independently is H; (b)R 4b , R 4c and R 4d Each independently is H; (c)R 4a , R 4c and R 4e are each independently H; or (d) R 4a , R 4b , R 4c , R 4d and R 4e Neither is H.

15. A compound according to any one of claims 12-14, wherein one of the following applies: (a)R4a and R 4e are the same; (b)R 4b and R 4d are the same; (c)R 4a , R 4c and R 4e are the same; (c)R 4a , R 4b , R 4c , R 4d and R 4e are the same.

16. A compound according to any one of claims 12-15, wherein one of the following applies: (a)R 4a is selected from C1-C6 alkyl and N(C1-C6 alkyl)2, and R 4b , R 4c , R 4d and R 4e Each independently is H; (b)R 4a and R 4e are each independently C1-C6 alkyl, and R 4b , R 4c and R 4d Each independently is H; (c)R 4a and R 4e are each independently a C1-C6 alkoxy group, and R 4b , R 4c and R 4d Each independently is H; (d) R 4b and R 4d are each independently C1-C6 alkyl or phenyl, and R 4a , R 4c and R 4e Each independently is H; (e)R 4a , R 4c and R 4e are each independently C1-C6 alkyl or C3-C8 cycloalkyl, and R 4b and R 4d Each independently is H; (f)R 4a , R 4c and R 4e are each independently a C1-C6 alkoxy group, and R 4b and R 4d are each independently H; or (g)R 4a , R 4b , R 4c , R 4d and R 4e Each is independently a C1-C6 alkyl group.

17. A compound according to any one of claims 1 to 16, wherein R 4 Selected from:

18. A compound according to any one of claims 1 to 11, wherein R 4 It is cyclohexyl or adamantyl.

19. The compound according to any one of claims 1 to 18, wherein X is selected from halogen, OS(=O)2R A 、OC(=O)R A 、N(C(=O)R A )2. Tetracoordinated borate and hexacoordinated phosphorus.

20. The compound according to any one of claims 1-19, wherein X is Cl.

21. A compound according to any one of claims 1 to 20, selected from the following: 5-(2,6-Dimethylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 2-Mesityl-5-(2,4,6-triethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(2,4,6-triethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(2,3,4,5,6-pentamethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-Mesityl-5-(2,4,6-tricyclohexylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(2,4,6-tricyclohexylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(2,6-diisopropylphenyl)-2-(2,6-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(2,6-Diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 2,5-Bis(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-Cyclohexyl-5-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(2,6-dimethoxyphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(2,4,6-trimethoxyphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(2-(Dimethylamino)phenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(2-(dimethylamino)phenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-Bis-diphenylmethyl-4-methylphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-Bis-diphenylmethyl-4-methoxyphenyl)-5-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-Bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-Bis(diphenylmethyl)-4-fluorophenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-Cyclohexyl-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 5-Cyclohexyl-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(Adamantane-1-yl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 5-(Adamantane-1-yl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(3,5-dimethylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 2-(2,6-diisopropylphenyl)-5-(3,5-dimethylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(3,5-di-tert-butylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 5-(3,5-di-tert-butylphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-([1,1':3',1"-terphenyl]-5'-yl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; 5-([1,1':3',1"-terphenyl]-5'-yl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride; 5-(2-isopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-2-ium chloride; and 2-(2,6-Diisopropylphenyl)-5-(2-isopropylphenyl)imidazo[1,5-a]pyridin-2-ium chloride salt.

22. A compound of formula (II): in: M is a transition metal; L is a ligand of M, wherein each occurrence of L may be the same or different; Each occurrence of is a single bond or a double bond, There is no more than one bonded C atom and N atom It is a double bond; T 1 Is N or CR 1a ; T 2 Is N or CR 1b ; T 3 Is N or CR 1c ; R 1a , R 1b and R 1c Each is independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A 、N(R A )(R B )、C(=O)R A 、C(=O)N(R A )(R B )、C(=O)OR B 、N(R A )S(=O)2R B 、S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl, Where R 1a , R 1b and R 1c Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group, Among them, R 1a , R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 heterocyclic or optionally substituted C6-C 10 Aryl; R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 Heterocyclic group; R 3 is selected from optionally substituted C6-C 10 aryl, optionally substituted C2-C8 heteroaryl and optionally substituted C3-C8 cycloalkyl, Where R 3 Each optional substituent in is independently selected from at least one of the following: H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, OR A , N(R A )(R B )、C(=O)R A 、C(=O)N(R A )(R B )、C(=O)OR B 、N(R A )S(=O)2R B 、 S(=O)2N(R A ), optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C 12 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl, wherein the C1-C6 alkyl, C3-C8 cycloalkyl, C2-C 12 The heterocyclyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl groups are each optionally substituted with at least one substituent selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl groups, and C2-C 12 Heterocyclic group; R 4 is selected from optionally substituted C3-C 12 Cycloalkyl and phenyl substituted by at least one substituent selected from the group consisting of C1-C6 alkyl, C3-C 12 Cycloalkyl, C1-C6 alkoxy, phenyl and N(R A )(R B ), Wherein the C3-C 12 Each optional substituent in the cycloalkyl group is at least one selected from the group consisting of halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group; X is a counter anion; R A and R B Each is independently selected from H, C1-C6 alkyl, C1-C3 haloalkyl, C2-C6 alkenyl, benzyl, naphthyl, C4-C 10 Heteroaryl and phenyl, where R A and R B Each substituent in is optionally substituted with at least one substituent selected from the group consisting of CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl and halogen; m is an integer selected from 0, 1, 2 and 3; n is an integer selected from 0, 1 and 2; If T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is selected from Cu, Ag and Au, and R 4 is 2,4,6-triisopropylphenyl, then R 3 Not 2,6-diisopropylphenyl or 2,4,6-trimethylphenyl; If T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Cu, and R 4 is 2,4,6-trimethylphenyl, then R 3 Not 2,4,6-trimethylphenyl, 2,6-diisopropylphenyl, adamantyl, 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl or (2-(2-methoxyethoxy)ethoxy)phenyl; If T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Pd, R 4 is 2,4,6-trimethylphenyl, and L is 3-chloropyridyl or pyridyl, then R 3 Not 2,4,6-trimethylphenyl or 4-(2-(2-methoxyethoxy)ethoxy)-2,6-dimethylphenyl; If T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Pd, R 4 is 2,4,6-triisopropylphenyl, and X is an allyl anion (ie, vinylmethanol), then R 3 is not 2,4,6-trimethylphenyl; and If T 1 It is CH, T 2 It is CH, T 3 It is CH, R 2 is H, M is Au, and R 4 is 5-tetrahydroisoquinolinyl, then R 3 Not 2,6-diisopropylphenyl.

23. The compound according to claim 22, wherein at least one of the following applies: (a)T 1 Yes CR 1a ; (b)T 2 Yes CR 1b ;as well as (c)T 3 Yes CR 1c .

24. The compound according to claim 22 or 23, wherein at least one of the following is present: (a)R 1a , R 1b and R 1c At least one of them is H; (b)R 1a , R 1b and R 1c At least two of are H; and (c)R 1a , R 1b and R 1c Each of them is H.

25. A compound according to any one of claims 22 to 24, wherein R 2 It's H.

26. A compound according to any one of claims 22 to 25, wherein R 3 yes: in: R 3a , R 3b , R 3c , R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy, Where R 3a , R 3b , R 3c , R 3d and R 3e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

27. The compound according to claim 26, wherein R 3a , R 3b , R 3c , R 3d and R 3e Each is independently selected from H, methyl, isopropyl, diphenylmethyl, methoxy and fluorine.

28. The compound according to claim 26 or 27, wherein one of the following is applicable: (a)R 3b and R 3d are each independently H; or (b)R 3b , R 3c and R3d Each independently is H.

29. A compound according to any one of claims 26-28, wherein one of the following applies: (a)R 3a and R 3e are the same; or (b)R 3a , R 3c and R 3e are the same.

30. A compound according to any one of claims 26-29, wherein one of the following applies: (a)R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b , R 3c and R 3d It is H; (b)R 3a , R 3c and R 3e are each independently an optionally substituted C1-C6 alkyl group, and R 3b and R 3d is H; or (c)R 3a and R 3e are each independently an optionally substituted C1-C6 alkyl group, R 3c is selected from halogen and C1-C6 alkoxy, and R 3b and R 3d It's H.

31. A compound according to any one of claims 22-30, wherein R 3 Selected from:

32. A compound according to any one of claims 22-25, wherein R 3 It is cyclohexyl.

33. A compound according to any one of claims 22-32, wherein R 4 yes: in: R 4a , R 4b , R 4c , R 4d and R 4e each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy, Where R 4a , R 4b , R 4c , R 4d and R 4e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group.

34. The compound according to claim 33, wherein R 4a , R 4b , R 4c , R 4dand R 4e Each is independently selected from H, methyl, ethyl, isopropyl, cyclohexyl, tert-butyl, methoxy, isopropoxy, phenyl and dimethylamino.

35. A compound according to claim 33 or 34, wherein one of the following applies: (a)R 4b , R 4c , R 4d and R 4e Each independently is H; (b)R 4b , R 4c and R 4d Each independently is H; (c)R 4a , R 4c and R 4e are each independently H; or (d) R 4a , R 4b , R 4c , R 4d and R 4e Neither is H.

36. A compound according to any one of claims 33-35, wherein one of the following applies: (a)R 4a and R 4e are the same; (b)R 4b and R 4d are the same; (c)R 4a , R 4c and R 4e are the same; (c)R 4a , R 4b , R 4c , R 4d and R 4e are the same.

37. A compound according to any one of claims 33-36, wherein one of the following applies: (a)R 4a is selected from C1-C6 alkyl and N(C1-C6 alkyl)2, and R 4b , R 4c , R 4d and R 4e Each independently is H; (b)R 4a and R 4e are each independently C1-C6 alkyl, and R 4b , R 4c and R4d Each independently is H; (c)R 4a and R 4e are each independently a C1-C6 alkoxy group, and R 4b , R 4c and R 4d Each independently is H; (d) R 4b and R 4d are each independently C1-C6 alkyl or phenyl, and R 4a , R 4c and R 4e Each independently is H; (e)R 4a , R 4c and R 4e are each independently C1-C6 alkyl or C3-C8 cycloalkyl, and R 4b and R 4d Each independently is H; (f)R 4a , R 4c and R 4e are each independently a C1-C6 alkoxy group, and R 4b and R 4d are each independently H; or (g)R 4a , R 4b , R 4c , R 4d and R 4e Each is independently a C1-C6 alkyl group.

38. A compound according to any one of claims 22-37, wherein R 4 Selected from:

39. A compound according to any one of claims 22-32, wherein R 4 It is cyclohexyl or adamantyl.

40. The compound according to any one of claims 22-39, wherein X is selected from halogen, OS(=O)2R A 、OC(=O)R A 、N(C(=O)R A )2, tetracoordinate borate, hexacoordinate phosphorus, optionally substituted C6-C 10 Aryl and optionally substituted C2-C 10 Heteroaryl, wherein the C6-C 10Each optional substituent in aryl and C2-C8 heteroaryl is independently selected from halogen, CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C3-C8 cycloalkyl, phenyl and C2-C8 heterocyclyl.

41. A compound according to any one of claims 22-40, wherein X is selected from Cl, an allyl anion (i.e., vinyl methane), a tert-butyl indenyl anion (i.e., 1-tert-butyl inden-1-root and / or 3-tert-butyl inden-1-root) and an allyl benzene anion (i.e., 3-phenyl propene-3-root and / or 1-phenyl propene-3-root).

42. A compound according to any one of claims 22-41, wherein M is selected from Pd, Cu, Ag, Au, Ni, Pt, Co, Rh, Ir, Fe, Ru and Os.

43. The compound of claim 42, wherein M is selected from Pd, Cu, Ag and Rh.

44. according to the compound described in any one of claims 22-43, wherein L is selected from carbon monoxide (CO), optionally substituted C2-C 12 olefins, and optionally substituted C5-C 12 cycloolefin, optionally substituted benzylamine, optionally substituted C2-C8 heteroaryl, wherein the C2-C 12 Olefins, C5-C 12 Each optional substituent in cycloalkene, benzylamine and C2-C8 heteroaryl is independently selected from halogen, CN, NO2, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C3-C8 cycloalkyl, phenyl and C2-C8 heterocyclyl.

45. The compound of claim 44, wherein L is selected from cyclooctadiene (COD), carbon monoxide (CO), pyridine and 3-chloropyridine.

46. ​​A compound according to any one of claims 22-45, selected from the following: Cinnamyl[5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium chloride; Cinnamyl[2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; Cinnamyl[5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; 2-Dimethylaminomethylphenyl[2-(2,6-bis(benzhydryl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; 2-Acetamido-phenyl[2-(2,6-bis(benzhydryl-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; Cinnamyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; Allyl[2,5-dimesitylphenylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; Cinnamyl[2-(2,6-diisopropylphenyl)-5-mesitylimidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; 1-tert-Butyl-indenyl[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; Cinnamyl[2-mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) chloride; Pyridinium[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride; 3-Chloropyridinium[2-(2,6-diisopropylphenyl)-5-mesityl imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride; 3-Chloropyridinium[2-mesityl-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]palladium(II) dichloride; (2,5-dimesityl imidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride; (5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3(2H)-ylidene)gold(I) chloride; (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; (2-(2,6-bis(benzhydryl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; (5-(2,6-diisopropoxyphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride; (2-(2,6-bis(diphenylmethyl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride; (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)copper(I) chloride; (2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride; (2-(2,6-bis(diphenylmethyl)-4-methoxyphenyl)-5-mesityl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride; (2-(2,6-bis(benzhydryl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)silver(I) chloride; Cyclooctadiene[5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride; Dicarbonyl[5-(2,6-diisopropylphenyl)-2-mesityl imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride; Cyclooctadiene[2,5-dimesityl imidazo[1,5-a]pyridin-2-ylidene]rhodium(I) chloride; Dicarbonyl[2,5-dimesityl imidazo[1,5-a]pyridin-2-ylidene]rhodium(I) chloride; Cyclooctadiene[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride; Dicarbonyl[2-(2,6-bis(diphenylmethyl)-4-methylphenyl)-5-(2,4,6-triisopropylphenyl)imidazo[1,5-a]pyridin-3-ylidene]rhodium(I) chloride; (5-(2,4,6-triethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; Cinnamyl (5-(2,4,6-triethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)palladium(II) chloride; (5-(2,4,6-trimethylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; (5-(2,6-diisopropylphenyl)-2-(2,6-diisopropylphenyl)-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride; and (5-(2,6-Diisopropylphenyl)-2-cyclohexyl-2,3-dihydroimidazo[1,5-a]pyridin-3-yl)gold(I) chloride.

47. A method of promoting the reaction between a boronic acid and a nitroarene, the method comprising contacting the boronic acid and the nitroarene in the presence of a compound according to any one of claims 22 to 45 and a base, and optionally in the presence of a phase transfer catalyst.

48. A method for promoting a reaction between an alkyl sulfoxide and aniline, the method comprising contacting the alkyl sulfoxide and the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

49. A method for promoting the reaction between thiophenol and aniline, the method comprising contacting the thiophenol and the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

50. A method of promoting a reaction between an aryl halide and a hydrazine, the method comprising contacting the aryl halide and the hydrazine in the presence of a compound according to any one of claims 22 to 45 and a Lewis acid to provide an aryl hydrazine.

51. The method of claim 50, further comprising contacting the aryl hydrazine and a 1,3-diketone to provide a 1-phenylpyrazole.

52. A method of promoting the reaction of an aryl methanesulfonate or an aryl tosylate with boronic acid, the method comprising contacting the aryl methanesulfonate or the aryl tosylate with the boronic acid in the presence of a compound according to any one of claims 22 to 45 and a base.

53. A method for promoting the reaction of an aryl methanesulfonate or an aryl toluenesulfonate with aniline, the method comprising contacting the aryl methanesulfonate or an aryl toluenesulfonate with the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

54. A method of promoting a reaction between an arylsulfamate and a boronic acid, the method comprising contacting the arylsulfamate and the boronic acid in the presence of a compound according to any one of claims 22 to 45 and a base.

55. A method of promoting the reaction between an arylsulfamate and aniline, the method comprising contacting the arylsulfamate and the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

56. A method of promoting a reaction between an aryl halide and a hydroxide salt, the method comprising contacting the aryl halide and the hydroxide salt in the presence of a compound according to any one of claims 22 to 45.

57. A method for promoting the reaction between an aryl methyl sulfide and aniline, the method comprising contacting the aryl methyl sulfide and the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

58. A method for promoting the reaction between an aryl sulfoxide and aniline, the method comprising contacting the aryl sulfoxide and the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

59. A method of promoting a reaction between an amine and an aryl chloride, the method comprising contacting the amine and the aryl chloride in the presence of a compound according to any one of claims 22 to 45 and a base.

60. A method of promoting a reaction between an aryl chloride and a boronic acid, the method comprising contacting the aryl chloride and the boronic acid in the presence of a compound according to any one of claims 22 to 45 and a base.

61. A method of promoting a reaction between an aryl fluoride and an aniline, the method comprising contacting the aryl fluoride and the aniline in the presence of a compound according to any one of claims 22 to 45 and a base.

62. A method of promoting a reaction between an alkyne and a nitroarene, the method comprising contacting the alkyne and the nitroarene in the presence of a compound according to any one of claims 22 to 45 and a reducing agent, wherein the contacting optionally further occurs in the presence of a Lewis acid.

63. The method of any one of claims 46-62, wherein in the compound of any one of claims 22-45, M is Pd.

64. The method of any one of claims 46-63, wherein at least one of the following applies: (a) the boric acid is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one borate or boronic acid moiety, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (b) the nitroaromatic hydrocarbon is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one NO2 moiety and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (c) the alkyl sulfoxide is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is partially substituted by at least one S(═O) (optionally substituted C1-C6 alkyl), and is further optionally substituted by at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (d) the aniline is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one NH2 moiety and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (e) the thiophenol is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one thiol moiety and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (f) the aryl halide is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted by at least one halogen selected from Cl, Br and I, and is further optionally substituted by at least one substituent selected from the following: C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (g) the aryl toluene sulfonate is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10The aryl or C2-C8 heteroaryl is substituted with at least one tosyloxy moiety, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (h) the aryl methanesulfonate is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one methanesulfonyloxy moiety, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (i) The arylaminosulfonate is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one sulfamate moiety and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (j) the aryl chloride is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10The aryl or C2-C8 heteroaryl is substituted with at least one Cl, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (k) The aryl methyl sulfide is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one methylthio moiety (i.e., -SCH3), and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (l) The aryl sulfoxide is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted by at least one substituent selected from the group consisting of S(═O) (optionally substituted C1-C6 alkyl), S(═O) (optionally substituted C6-C 10 aryl) and S(═O)(optionally substituted C2-C8 heteroaryl), and further optionally substituted by at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2; (m) the amine is selected from N(optionally substituted C1-C6 alkyl)2, N(optionally substituted C1-C6 alkyl) (optionally substituted C6-C 10 Aryl), N (optionally substituted C6-C 10 aryl)2 and optionally substituted C2-C8 heterocycloalkyl, wherein the heterocycloalkyl contains at least one secondary amine; (n) The aryl bromide is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one Br, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl), and C(=O)N(C1-C6 alkyl); and (o) The aryl fluoride is C6-C 10 aryl or C2-C8 heteroaryl, wherein the C6-C 10 The aryl or C2-C8 heteroaryl is substituted with at least one F, and is further optionally substituted with at least one substituent selected from the group consisting of C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 haloalkyl, C1-C6 alkyl, C3-C 12 Cycloalkyl, C2-C 10 Heterocyclyl, C2-C6 alkenyl, phenyl, naphthyl, NH2, N(C1-C6 alkyl)2, halogen, OH, CN, NO2, C(=O)OH, C(=O)O(C1-C6 alkyl), C(=O)NH2, C(=O)NH(C1-C6 alkyl) and C(=O)N(C1-C6 alkyl)2.

65. A method for preparing a compound of formula (IV): in: T 1 Is N or CR 1a ; T 2 Is N or CR 1b ; T 3 Is N or CR 1c ; R 1a , R 1b and R 1c each independently selected from H, halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, CN, NO2, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C2-C8 heterocyclyl, optionally substituted C2-C6 alkenyl, optionally substituted benzyl, optionally substituted phenyl and optionally substituted naphthyl, Where R 1a , R 1b and R 1c Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group, Among them, R 1a , R 1b and R 1c Two adjacent substituents of may combine with the carbon atom to which they are attached to form an optionally substituted C5-C 12 Cycloalkyl, optionally substituted C2-C 12 heterocyclic or optionally substituted C6-C 10 Aryl; R 2 Selected from H, C1-C6 alkyl, C6-C 10 Aryl and C2-C 12 Heterocyclic group; R 3a , R 3b , R 3c , R 3d and R 3e are each independently selected from H, halogen, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy, Where R 3a , R 3b , R 3c , R 3d and R 3e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 Heterocyclic group; R 4a , R 4b , R 4c , R 4d and R 4e each independently selected from H, halogen, N(optionally substituted C1-C6 alkyl)2, optionally substituted C1-C6 alkyl and optionally substituted C1-C6 alkoxy, Where R 4a , R 4b , R 4c , R 4d and R 4e Each of the optional substituents in each of is independently selected from halogen, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkyl, C2-C6 alkenyl, benzyl, phenyl and naphthyl, and C2-C 12 heterocyclyl; and X is a counter ion; The method comprises causing (Z): With (Y): Contact in the presence of paraformaldehyde and acid.

66. The method of claim 65, wherein (Z) is obtained by causing (X): With (W): Prepared by reacting in the presence of a transition metal catalyst; Where X 1 and X 2 Each is independently selected from Cl, Br and I.

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