Ligands for transition metal catalysts

Abstract

A new class of sterically extremely large, easily prepared N-heterocyclic carbene (NHC) ligands of Formula I or salts, solvates, geometric isomers or stereoisomers thereof is provided herein. The ligands are readily synthesized using cost-effective, modular alkylation of the commercially available chemical aniline. The NHC ligands form effective catalysts with transition metals such as Pd.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 958,565, filed on January 8, 2020, entitled “LIGANDS FOR TRANSITION METALCATALYSTS,” the disclosure of which is incorporated herein by reference in its entirety.

[0003] Statement Regarding Federally Funded Research

[0004] This invention was made with government support under Grants CHE-1650766 from the National Science Foundation and GM133326 from the National Institutes of Health. The government has certain rights in this invention. Background Art

[0005] N-Heterocyclic carbenes (NHCs) have emerged as very valuable ligands in homogeneous catalysis. The widespread application of NHC ligands is a result of the strong σ-donation of the carbene center and the variable steric bulk of the wingtip groups, which are often not easily accessible using other types of ligands, including phosphines. Furthermore, by exploiting the flexible steric bulk of the wingtips, NHC ligands allow for kinetic stabilization of metals and intermediates in unusual oxidation states, while their well-defined topology has been widely applied to fine-tune the reactivity of metal centers.

[0006] In this context, the most important NHC ligands in the field of homogeneous catalysis to date are the bulky IPr( Figure 1 , 1). Although it is easily synthesized from Dipp (Dipp = 2,6-diisopropylaniline), the problem lies in the preparation of the Dipp precursor. The preparation of Dipp is severely limited by the challenge of controlling the selectivity of alkylation, and the most common industrial route adopts a lengthy and inflexible route through phenol alkylation.

[0007] Therefore, there remains a need for economically and synthetically available transition metal ligands to form efficient and stable catalysts. The present disclosure addresses and solves this need. Summary of the invention

[0008] Provided herein are compounds of Formula I having the following structure:

[0009]

[0010] In certain embodiments, is a single bond or a double bond. In certain embodiments, A1 and A2 are each independently C 6-18 Aryl or C 6-18In certain embodiments, R 1 and R 2 are each independently C substituted by at least one aryl or heteroaryl 1-3 Alkyl, where R 1 and R 2 The aryl or heteroaryl in the formula (a) is optionally substituted by at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 In certain embodiments, R 3 and R 4 are each independently hydrogen, optionally substituted C 3-10 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C12 heteroaryl or optionally substituted C 1-12 Acyl) or OC 1-12 Alkyl, wherein optionally the substituents independently include at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 In certain embodiments, R 3 and R 4 Together with the rings to which they are attached, they form C 4-20 Cycloalkyl, C 6-20 Aryl or C 6-20 Heteroaryl, each of which is independently optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 In certain embodiments, X is a counter anion. In certain embodiments, R is independently hydrogen or C 1-10 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl and optionally substituted C 1-10 In some embodiments, k is 1, 2, 3 or 4. In some embodiments, m is an integer from 0 to 6. In some embodiments, n is an integer from 0 to 6. In some embodiments, if A1 and A2 are phenyl, at least one of m or n is 3, 4 or 5.

[0011] Also provided are compounds of formula II or salts thereof:

[0012]

[0013] In certain embodiments, M is an element of Group VIII to Group XVI with an atomic weight greater than 25. In certain embodiments, L is a ligand of M, wherein L may be the same or different at each occurrence. In certain embodiments, p is an integer from 0 to 5. In certain embodiments, is a single bond or a double bond. In certain embodiments, A1 and A2 are each independently C 6-10 Aryl or C 6-10 In certain embodiments, R 1 and R 2are each independently C substituted by at least one aryl or heteroaryl 1-3 Alkyl, where R 1 and R 2 The aryl or heteroaryl in the formula (a) is optionally substituted by at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 In certain embodiments, R 3 and R 4 are each independently hydrogen, optionally substituted C 3-10 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl) or OC1-12 Alkyl, wherein the optional substitution independently comprises at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 In certain embodiments, R 3 and R 4 Together with the rings to which they are attached, they form C 4-20 Cycloalkyl, C 6-20 Aryl or C 6-20 Heteroaryl, each of which is independently optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 In certain embodiments, R is independently hydrogen or C 1-10 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl or optionally substituted C 1-10 In some embodiments, k is 1, 2, 3 or 4. In some embodiments, m is an integer from 0 to 5. In some embodiments, n is an integer from 0 to 5. In some embodiments, if A1 and A2 are phenyl, at least one of m or n is 3, 4 or 5. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] The drawings generally illustrate various embodiments of the application by way of example and not by way of limitation.

[0015] Figure 1 Various sterically demanding N-heterocyclic carbenes for catalysis are shown.

[0016] Figure 2 The X-ray crystal structure of complex 9 is shown. Two views: front view (upper panel); side view (lower panel). Hydrogen atoms are omitted for clarity. The bond lengths are chosen and bond angles [°]: Au–C1, 1.972; Au–Cl, 2.2768; C1–N1, 1.356; C3–N1, 1.442(2); C1–Au–Cl, 180.0; N1–C1–N1, 104.9; C3–N1–C1, 122.7; N1–C1–Au, 127.5. Note the symmetry across the Cl-Au-C1 axis in 9.

[0017] Figure 3 The X-ray crystal structure of complex 13 is shown. Two views: front view (upper panel); side view (lower panel). Hydrogen atoms are omitted for clarity. The bond lengths are chosen and bond angles [°]: Pd–C1, 2.044(4); Pd–Cl, 2.374(1); Pd–C49, 2.121(4); Pd–C50, 2.130(6); Pd–C51, 2.210(7); C1–N1, 1.364(5); C1–N2, 1.368(4); C4–N1, 1.452(4); C58–N2, 1.440(5); C 1–Pd–C49, 103.2(2); C1–Pd–C50, 138.5(2); C1–Pd–C51, 169.4(2); C49–Pd–C51, 67.0(2 ); C1–Pd–Cl, 93.7(1); N1–C1–N2, 103.3(3); C4–N1–C1, 124.9(3); C58–N2–C1, 124.7(3).

[0018] Figure 4 Topographic stereograms of [Au(IPr#)Cl](9) and [Pd(IPr#)(cin)Cl](13) are shown, with %V for each quadrant bur . DETAILED DESCRIPTION

[0019] 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.

[0020] Throughout this document, values ​​expressed in range format should be interpreted in a flexible manner to include not only the values ​​explicitly listed as range limits, but also all individual values ​​or subranges contained 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 as including 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 specified range. Unless otherwise specified, the statement "about X to Y" has the same meaning as "about X to about Y". Similarly, unless otherwise specified, the statement "about X, Y or about Z" has the same meaning as "about X, about Y or about Z".

[0021] In this document, unless the context clearly dictates otherwise, the terms "a", "an", or "the" are used to include one or more. Unless otherwise specified, the term "or" is used to refer to a non-exclusive "or". The statements "at least one of A and B" or "at least one of A or B" have the same meaning as "A, B, or A and B". In addition, it should be understood that the expressions or terms used herein are for descriptive purposes only and not for limiting purposes unless otherwise defined. The use of any section headings is to assist in reading the document and should not be construed as limiting; 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 incorporated by reference individually.

[0022] In the methods described herein, actions may be performed in any order unless a time or order of operations is explicitly enumerated. In addition, specified actions may be performed simultaneously unless explicit declarative language indicates that they are performed separately. For example, a claimed action of doing X and a claimed action of doing Y may be performed simultaneously in a single operation, and the resulting process will fall within the literal scope of the claimed method.

[0023] definition

[0024] As used herein, the term "about" can allow a degree of variability in a value or range, for example, within 10%, within 5%, or within 1% of the limits of the stated value or stated range, and includes the exact stated value or range.

[0025] As used herein, the term "substantially" means mostly or mainly, 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 of" can mean free of or having an insignificant amount such that the amount of material present does not affect the material properties of the composition including the material, such that the composition contains about 0 wt % to about 5 wt % of the material or about 0 wt % to about 1 wt % or about 5 wt % or less or less than, equal to or more 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. The term "substantially free" can mean having an insignificant amount, such that the composition contains 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 more 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 %.

[0026] As used herein, the term "organic group" refers to any carbon-containing functional group. Examples may include oxygen-containing groups such as alkoxy, aryloxy, aralkyloxy, oxo (carbonyl) groups; carboxyl groups, including carboxylic acids, carboxylates and carboxylates; sulfur-containing groups such as alkyl, aryl thioether groups, etc.; and other heteroatom-containing groups. 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 examples including other carbon atoms) or a carbyl moiety, and wherein the carbyl moiety can be substituted or unsubstituted.

[0027] The term "substituted" used with a molecule or organic group as defined herein 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 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), carboxyl groups including carboxylic acids, carboxylates, and carboxylates; sulfur atoms in groups such as thiol, alkyl and aryl thioether, sulfoxide, sulfone, sulfonyl, and sulfonamide; nitrogen atoms in groups such as amines, hydroxylamines, nitriles, nitro, 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, SOR, SO2R, 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 and C(=NOR)R, wherein R can be hydrogen or a carbonyl moiety; for example, R can be hydrogen, (C1-C 100 ) a hydrocarbon group, an alkyl group, an acyl group, a cycloalkyl group, an aryl group, an aralkyl group, a heterocyclic group, a heteroaryl group or a heteroaralkyl group; or wherein the two R groups bonded to a nitrogen atom or adjacent nitrogen atoms may form a heterocyclic group together with one or more nitrogen atoms.

[0028] As used herein, the term "alkyl (alkyl)" refers to straight and branched alkyl and cycloalkyl groups having 1 to 40 carbon atoms, 1 to about 20 carbon atoms, 1 to 12 carbons, or in some embodiments 1 to 8 carbon atoms. Examples of straight chain alkyl groups include those having 1 to 8 carbon atoms, such as methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl and n-octyl. Examples of branched alkyl groups include, but are not limited to, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl, isopentyl and 2,2-dimethylpropyl. As used herein, the term "alkyl (alkyl)" includes n-alkyl, isoalkyl and anteisoalkyl and other branched forms of alkyl. Representative substituted alkyl groups can be substituted once or multiple times by any group listed herein, such as amino, hydroxyl, cyano, carboxyl, nitro, sulfenyl, alkoxy and halogen groups.

[0029] As used herein, the term "alkenyl" refers to straight and branched chains and cyclic alkyl groups as defined herein, except that there is at least one double bond between two carbon atoms. Therefore, alkenyl has 2 to 40 carbon atoms or 2 to about 20 carbon atoms or 2 to 12 carbon atoms or 2 to 8 carbon atoms in some embodiments. Examples 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, etc.

[0030] As used herein, the term "alkynyl" refers to straight and branched alkyl groups, except that there is at least one triple bond between two carbon atoms. Thus, alkynyl groups have 2 to 40 carbon atoms, 2 to about 20 carbon atoms, or 2 to 12 carbons, or in some embodiments 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), etc.

[0031] As used herein, the term "acyl" refers to a group containing a carbonyl moiety, wherein the group is bonded via a carbonyl carbon atom. The carbonyl carbon atom is bonded to a hydrogen forming a "formyl" group or to another carbon atom, which may be a part of an alkyl, aryl, aralkylcycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroaralkyl, etc. The acyl group may 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 may include double or triple bonds within the meaning of this article. Acryloyl is an example of an acyl group. Acyl groups may also include heteroatoms within the meaning of this article. Nicotinoyl (pyridyl-3-carbonyl) is an example of an acyl group within the meaning of this article. 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.

[0032] 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, and in other embodiments, the number of ring carbon atoms is 3 to 4, 5, 6, or 7. Cycloalkyl further includes polycyclic cycloalkyl groups, such as, but not limited to, norbornyl, adamantyl, bornyl, camphenyl, isocamphenyl, and carenyl groups, and fused rings, such as, but not limited to, decahydronaphthyl, etc. Cycloalkyl groups also include rings substituted with straight or branched 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 or mono-, di- or tri-substituted norbornyl or cycloheptyl, which may be substituted, for example, with amino, hydroxyl, cyano, carboxyl, nitro, sulfenyl, alkoxy and halogen groups. The term "cycloalkenyl", used alone or in combination, means a cyclic alkenyl group.

[0033] 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, heptenyl, biphenyl, indacenyl, fluorenyl, phenanthrenyl, triphenylene, pyrenyl, naphthyl, In some embodiments, the aryl group contains about 6 to about 14 carbons 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 any one or more substituted phenyl groups in the 2-, 3-, 4-, 5-, or 6-positions of the phenyl ring or any one or more substituted naphthyl groups in the 2-8-positions thereof.

[0034] As used herein, the term "aralkyl" refers to an alkyl group as defined herein, wherein a hydrogen bond 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 phenethyl groups and fused (cycloalkylaryl) alkyl groups, such as 4-ethyl-indanyl. Aralkenyl groups are alkenyl groups as defined herein, wherein a hydrogen bond or carbon bond of the alkyl group is replaced by a bond to an aryl group as defined herein.

[0035] As used herein, the term "heterocyclyl" refers to aromatic and non-aromatic ring compounds including three or more ring members, one or more of which are heteroatoms, such as but not limited to N, O and S. Therefore, the heterocyclyl group can be a cycloheteroalkyl or heteroaryl group, or if it is polycyclic, it can be any combination thereof. In some embodiments, the heterocyclyl group includes 3 to about 20 ring members, and other such groups have 3 to about 15 ring members. The heterocyclyl group named as C2-heterocyclyl can be a 5-ring with two carbon atoms and three heteroatoms, a 6-ring with two carbon atoms and four heteroatoms, etc. Similarly, the C4-heterocyclyl group can be a 5-ring with one heteroatom, a 6-ring with two heteroatoms, etc. The number of carbon atoms plus the number of heteroatoms is equal to the total number of ring atoms. The heterocyclyl ring can also include one or more double bonds. The heteroaryl ring is an embodiment of the heterocyclyl group. The phrase "heterocyclyl group" includes fused ring species, which include those comprising fused aromatic and non-aromatic groups. For example, dioxolane and benzodioxolane ring systems (methylenedioxyphenyl ring systems) are heterocyclyls within the meaning of this document. The phrase also includes polycyclic ring systems containing heteroatoms, such as, but not limited to, quinoline. Heterocyclyls may be unsubstituted or may be substituted as discussed herein. Heterocyclic groups include, but are not limited to, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridinyl, thiophenyl, benzothiophenyl, benzofuranyl, dihydrobenzofuranyl, indolyl, dihydroindolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridinyl, isoxazolopyridinyl, thianaphthalenyl, 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 quinolinyl, which are 2-, 3-, 4-, 5-, or 6-substituted or disubstituted with those groups listed herein.

[0036] As used herein, the term "heteroaryl" refers to an aromatic ring compound containing 5 or more ring members, one or more of which are heteroatoms, such as but not limited to N, O and S; for example, a heteroaryl ring can have 5 to about 8-12 ring members. Heteroaryl is a variety of heterocyclic groups with aromatic electronic structures. The heteroaryl group named C2-heteroaryl can be a 5-ring with two carbon atoms and three heteroatoms, a 6-ring with two carbon atoms and four heteroatoms, etc. Similarly, a C4-heteroaryl can be a 5-ring with one heteroatom, a 6-ring with two heteroatoms, etc. The sum of the number of carbon atoms plus the number of heteroatoms is equal to the total number of ring atoms. Heteroaryl includes but is not limited to groups, such as pyrrolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, pyridyl, phenylthio, benzophenylthio, benzofuranyl, indolyl, azaindolyl, indazolyl, benzimidazolyl, azabenzimidazolyl, benzoxazolyl, benzothiazolyl, benzothiadiazolyl, imidazopyridyl, isoxazolopyridyl, thionaphthyl, purinyl, xanthinyl, adeninyl, guaninyl, quinolyl, isoquinolyl, tetrahydroquinolyl, quinoxalinyl and quinazolinyl. Heteroaryl can be unsubstituted or can be replaced by groups discussed herein. Representative substituted heteroaryl can be replaced once or many times by groups such as those listed herein.

[0037] 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), phenylthio (2-phenylthio, 3-phenylthio), furanyl (2-furanyl, 3-furanyl), 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), phenylthio (2-benzo[b]phenylthio, 3-benzo[b]phenylthio, 4-benzo[b]phenylthio, 5-benzo[b]phenylthio, 6-benzo[b]phenylthio, 7-benzo[b]phenylthio), 2,3-dihydro-benzo[b]phenylthio, (2-(2,3-dihydro-benzo[b]phenylthio), 3-(2,3-dihydro-benzo[b]phenylthio), 4-(2,3-dihydro-benzo[b]phenylthio), 5-(2,3-dihydro-benzo[b]phenylthio), 6-(2,3-dihydro-benzo[b]phenylthio), 7-(2,3-dihydro-benzo[b]phenylthio),3-dihydro-benzo[b]phenylthio), 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-benzimidazolyl, 6-benzimidazolyl, imidazolyl, 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 (10,11-dihydro-5H-dibenzo[b,f]azepine -1-yl, 10,11-dihydro-5H-dibenzo[b,f]azepine -2-yl, 10,11-dihydro-5H-dibenzo[b,f]azepine -3-yl, 10,11-dihydro-5H-dibenzo[b,f]azepine -4-yl, 10,11-dihydro-5H-dibenzo[b,f]azepine -5-yl) etc.

[0038] As used herein, the term "heterocyclylalkyl" refers to an alkyl group as defined herein, wherein a hydrogen or carbon bond of the alkyl group as defined herein is replaced by a bond connected 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.

[0039] The term "heteroarylalkyl" as used herein refers to an alkyl group as defined herein wherein a hydrogen bond or a carbon bond of the alkyl group is replaced by a bond to a heteroaryl group as defined herein.

[0040] As used herein, the term "alkoxy" refers to an oxygen atom and arts The alkyl (including cycloalkyl) of definition is connected.The example of straight chain alkoxy includes but is not limited to methoxyl group, ethoxyl group, propoxyl group, butoxyl group, amyloxy group, hexyloxy group etc.The example of branched chain alkoxy includes but is not limited to isopropoxy, sec-butoxy, tert-butoxy, isopentyloxy group, isohexyloxy group etc.The example of cyclic alkoxy includes but is not limited to cyclopropyloxy, cyclobutyloxy, cyclopentyloxy group, cyclohexyloxy group etc.Alkoxy group can comprise about 1 to about 12, about 1 to about 20 or about 1 to about 40 carbon atoms 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 alkoxy groups within this paper's meaning, as the methylenedioxy in the context that two adjacent atoms of structure are replaced by it.

[0041] 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, heterocyclic amines, 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.

[0042] As used herein, the term "amino group" refers to a group of the form -NH2, -NHR, -NR2, -NR3 + A substituent, wherein each R is independently selected, and the respective protonated form, -NR3 + Except for, it cannot be protonated. Therefore, any compound substituted by amino group can be regarded as amine. "Amino group" within the meaning of this article can be primary amino group, secondary amino group, tertiary amino group or quaternary amino group. "Alkylamino" includes monoalkylamino, dialkylamino and trialkylamino.

[0043] As used herein, unless otherwise stated, the terms "halo," "halogen," or "halide" group, by itself or as part of another substituent, refers to a fluorine, chlorine, bromine, or iodine atom.

[0044] 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, etc.

[0045] As used herein, the term "epoxy-functional" or "epoxy-substituted" refers to a functional group in which an oxygen atom (the 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, glycidoxypropyl, 2-epoxypropoxyethyl, 3-epoxypropoxypropyl, 4-epoxypropoxybutyl, 2-(epoxycarbonyl)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.

[0046] As used herein, the term "monovalent" refers to a substituent that is attached to the substituted molecule via a single bond. When a substituent is monovalent, such as F or Cl, it is bonded to the atom it replaces via a single bond.

[0047] As used herein, the term "hydrocarbon" or "hydrocarbyl" refers to a molecule or functional group comprising carbon and hydrogen atoms. The term may also refer to a molecule or functional group that typically comprises carbon and hydrogen atoms but in which all hydrogen atoms are replaced by other functional groups.

[0048] As used herein, the term "hydrocarbyl" refers to a functional group derived from a linear, branched or cyclic hydrocarbon and may be an alkyl, alkenyl, alkynyl, aryl, cycloalkyl, acyl or any combination thereof. Hydrocarbyl may be represented by (C a -C b )alkyl, wherein a and b are integers and mean having any one of a to b carbon atoms. For example, (C1-C4)alkyl means that the alkyl group can be methyl (C1), ethyl (C2), propyl (C3) or butyl (C4), and (C0-C b ) alkyl means in certain embodiments there is no alkyl. In certain embodiments, the alkyl is an optionally substituted C 1-12In certain embodiments, the hydrocarbon group is an optionally substituted C 2-12 In certain embodiments, the alkyl group is an optionally substituted C 2-12 In certain embodiments, the alkyl group is an optionally substituted C 3-12 In certain embodiments, the hydrocarbon group is an optionally substituted C 1-12 In certain embodiments, the hydrocarbon group is an optionally substituted C 1-12 In certain embodiments, the hydrocarbon group is an optionally substituted C 6-14 Aryl and / or optionally substituted C 6-12 Aryl and / or optionally substituted C 6-10 In certain embodiments, the hydrocarbon group is an optionally substituted C2-C 12 In certain embodiments, the alkyl group is an optionally substituted C4-C 12 In certain embodiments, the alkyl group is an optionally substituted C 1-12 Acyl.

[0049] 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.

[0050] As used herein, the term "independently selected from" means that the referenced groups are the same, different, or a mixture thereof, unless the context clearly indicates otherwise. Therefore, under this definition, the phrase "X 1 , X 2 and X 3 "independently selected from inert gases" would include where for example X 1 , X 2 and X 3 are the same, where X 1 , X 2 and X 3 are all different, among which X 1 and X 2 Same but X 3 different situations, and other similar permutations.

[0051] As used herein, the term "room temperature" refers to a temperature of about 15°C to 28°C.

[0052] As used herein, the term "standard temperature and pressure" refers to 20°C and 101 kPa.

[0053] Preparation of compounds

[0054] Formula I-III or other compounds described herein 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 the compound(s) described herein and their preparation.

[0055] In various embodiments, provided are compounds of Formula I or salts, solvates, geometric isomers or stereoisomers thereof:

[0056]

[0057] in:

[0058] is a single bond or a double bond;

[0059] A1 and A2 are each independently C 6-18 Aryl or C 6-18 heteroaryl;

[0060] R 1 and R 2 are each independently C substituted by at least one aryl or heteroaryl 1-3 Alkyl, where R 1 and R 2 The aryl or heteroaryl in is independently optionally substituted; in certain embodiments, the optional substituents are independently at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 heteroaryl;

[0061] R 3 and R 4 are each independently hydrogen, optionally substituted C 3-10 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl) or OC 1-12 Alkyl; In certain embodiments, the optional substituents are independently at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 heteroaryl; or

[0062] R 3 and R 4 Together with the rings to which they are attached, they form C 4-20 Cycloalkyl, C 6-20 Aryl or C 6-20 heteroaryl, each of which is optionally substituted; in certain embodiments, the optional substituents are independently at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, S02R, SO2N(R)2, S03R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 heteroaryl;

[0063] X is a counter anion;

[0064] R is independently hydrogen or C 1-10 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl or optionally substituted C 1-10 acyl group);

[0065] k is 1, 2, 3, or 4;

[0066] m is an integer from 0 to 6;

[0067] n is an integer from 0 to 6; and

[0068] Provided that if A1 and A2 are phenyl, at least one of m or n is 3, 4 or 5.

[0069] In some embodiments, the compound of Formula I or a salt, solvate, geometric isomer or stereoisomer thereof is selected from:

[0070]

[0071]

[0072] In various embodiments, A1 and A2 are the same. In various embodiments, A1 is C 6-10 In some embodiments, A1 is phenyl. In other embodiments, A1 is naphthyl. In some embodiments, m is 3. In some embodiments, n is 3. In some embodiments, R 1 and R 2 In various embodiments, k is 1.

[0073] In some embodiments, R 1 is CH(aryl)2. In certain embodiments, R 1 is CH(phenyl)2. In certain embodiments, m is 3 and n is 3. In certain embodiments, X is a counter anion with a -1 or -2 charge. The type of X that can be used is not particularly limited, and any X that forms a stable complex with the compound of the present invention is suitable. In certain embodiments, X is selected from F, Cl, Br, I, OSO2R, OSO3R, OSO2CF3(OTf), and OC(=O)R, etc. In some embodiments, X is Cl.

[0074] In various embodiments, the compound of Formula I or a salt, solvate, geometric isomer or stereoisomer thereof is selected from:

[0075]

[0076] Where R 1Selected from CH(phenyl)2, CH(4-Me-C6H4), CH(4-t-Bu-C6H4)2, CH(4-MeO-C6H4)2, CH(4-CF3-C6H4)2, CH(3,5-dimethyl-C6H3)2, CH(3,5-bis(trifluoromethyl)-C6H3)2 and CH(3,5-difluoro-C6H3)2.

[0077] In one embodiment, a compound of Formula II or a salt, solvate, geometric isomer or stereoisomer thereof is provided:

[0078]

[0079] in:

[0080] M is an element of Groups VIII to XVI, and its atomic weight is greater than 25;

[0081] L is a ligand of M, wherein L may be the same or different at each occurrence;

[0082] p is an integer from 0 to 5; and

[0083] is a single bond or a double bond;

[0084] A1 and A2 are each independently C 6-10 Aryl or C 6-10 heteroaryl;

[0085] R 1 and R 2 are each independently C substituted by at least one aryl or heteroaryl 1-3 Alkyl, where R 1 and R 2 The aryl or heteroaryl in is independently optionally substituted; in certain embodiments, the optional substituents are independently at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 heteroaryl;

[0086] R 3 and R 4 are each independently hydrogen, optionally substituted C 3-10 cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl) or OC 1-12 Alkyl; In certain embodiments, the optional substituents are independently at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 heteroaryl; or

[0087] R 3 and R 4 Together with the rings to which they are attached, they form C 4-20 Cycloalkyl, C 6-20 Aryl or C 6-20 heteroaryl, each of which is optionally substituted; in certain embodiments, the optional substituents are independently at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, S02R, SO2N(R)2, S03R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 heteroaryl;

[0088] R is independently hydrogen or C 1-10 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-10Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl or optionally substituted C 1-10 acyl group);

[0089] k is 1, 2, 3, or 4;

[0090] m is an integer from 0 to 5;

[0091] n is an integer from 0 to 5; and

[0092] Wherein, if A1 and A2 are phenyl groups, at least one of m or n is 3, 4 or 5.

[0093] In various embodiments, M is selected from Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag, Re, Os, Ir, Pt and Au. In one embodiment, M is Pd. In one embodiment, M is a Group XVI element. In one embodiment, M is Se. In various embodiments, p is 0, 1, 2, 3, 4 or 5. When p is 0, the ligand L is absent.

[0094] Ligand L represents one or more ligands, the number of which is determined by the valence of the metal M and the variable 'p'. When there are more than one ligand L, each L can be the same or different. For example, when p is 2, (L)2 can be two identical ligands or two different ligands. In some embodiments, at least one L is an anionic ligand. In another embodiment, at least one L is a neutral ligand. The type of ligand L is not particularly limited, and any ligand L known in the art that forms a complex with M or serves as a counterion can be used. For example, but not limited to, anionic L includes halide, alkyl carboxylate, dicarboxylate, sulfate, sulfonate, CN, ferrocene, etc. In one embodiment, at least one L is Cl. Neutral L includes but is not limited to CO, cyclooctadiene (COD), π-coordinated olefins, π-coordinated aryl olefins, etc.

[0095] In various embodiments of the compound of Formula II, L is selected from acetoacetate, Cl, 3-Cl-pyridine, pyridine, NR-imidazole (R is Me, Et, Bu or Ph), cinnamyl, allyl, 1-R-indenyl (R = t-Bu, i-Pr, Et, Me, cyclohexyl, 1-adamantyl), Cp (cyclopentadienyl), aniline, 3-CF3-aniline, μ-Cl, μ-OH and 1,4-naphthoquinone; and p is 1, 2 or 3.

[0096] In various embodiments, the compound of formula II is selected from [Pd(NHC)(acetoacetate)Cl], [Pd(NHC)(3-Cl-pyridine)Cl2], [Pd(NHC)(pyridine)Cl2], [Pd(NHC)(N-R'-imidazole)Cl2], [Pd(NHC)(cinnamyl)Cl], [Pd(NHC)(allyl)Cl], [Pd(NHC)(1-R"-indenyl)Cl] (R=), [Pd(NHC)(Cp)Cl] (Cp=cyclopentadienyl), [Pd(NHC)(aniline)Cl2]), [Pd(NHC)(3-CF3-aniline)Cl2], [Pd(NHC)(μ-Cl)Cl]2, [Pd(NHC)(μ-OH)Cl]2, [Pd(NHC)(1,4-naphthoquinone)], [Ni(NHC)CpCl], [Ni(NHC)(PR A 3)X A 2], [Ni(NHC)(di-tert-butyl fumarate)2], [Ni(NHC)(methyl methacrylate)2], [Au(NHC)X B ], [Cu(NHC)X A ]、[Ag(NHC)X A ]、

[0097] Wherein NHC is selected from:

[0098]

[0099] R' is Me, Et, Bu or Ph,

[0100] R" is t-Bu, i-Pr, Et, Me, cyclohexyl or 1-adamantyl;

[0101] X A is Cl, Br, or I;

[0102] X B is Cl, Br, I, NTf2 or OTf;

[0103] PR A 3, where each R A Independently C1-8 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-8 Alkyl, optionally substituted C 2-8 Alkenyl, optionally substituted C 2-8 Alkynyl, optionally substituted C 3-8 Cycloalkyl, optionally substituted C 1-8 Heteroalkyl, optionally substituted C 1-8 alkyl, optionally substituted C6 aryl, optionally substituted C2-C8 heterocyclyl, optionally substituted C4-C8 heteroaryl or optionally substituted C 1-8 Acyl) or C 6-10 Aryl;

[0104] R 1 It is CH(phenyl)2, CH(4-Me-C6H4), CH(4-t-Bu-C6H4)2, CH(4-MeO-C6H4)2, CH(4-CF3-C6H4)2, CH(3,5-dimethyl-C6H3)2, CH(3,5-bis(trifluoromethyl)-C6H3)2 or CH(3,5-difluoro-C6H3)2.

[0105] In one embodiment, R A It is phenyl.

[0106] In one embodiment, a method for preparing a compound of Formula I or a salt, solvate, geometric isomer or stereoisomer thereof is provided. The method comprises making a compound having structure Compounds with cationic forms of R 1 to form a compound of formula III:

[0107]

[0108] The compound of formula III is condensed with (CHO)2 to form a diimine compound having the structure,

[0109] and

[0110] The diimine compound is cyclized to form a compound of Formula I or a salt, solvate, geometric isomer or stereoisomer thereof.

[0111] structure The compound is an arylamine or a heteroarylamine. The nature of A1-NH2 is not particularly limited, provided that a stable complex with a transition metal can be formed with the ligand described herein and the resulting transition metal complex has catalytic activity. Other suitable A1 moieties include anthracene (e.g., 1-aminoanthracene, 2-aminoanthracene, 9-aminoanthracene); aminobiphenyl (e.g., 4-aminobiphenyl); aminophenanthrene (e.g., 1-aminophenanthrene, 2-aminophenanthrene, 9-aminophenanthrene); aminopyrene (e.g., 1-aminopyrene, 2-aminopyrene); amino (e.g. 1-amino 2-Amino 6-Amino ); aminofluorene (e.g. 1-aminofluorene, 2-aminofluorene); naphthalene (e.g. 1-aminonaphthalene, 2-aminonaphthalene); acridine (e.g. 9-aminoacridine, 2-aminoacridine); quinoline (e.g. 8-aminoquinoline, 2-aminoquinoline, 5-aminoquinoline); and the like.

[0112] The cationic form of R 1 Including R 1 Solvated cations and cation-anion complexes R 1 , where R 1 Can react as a cation. Cation R 1 It can be prepared from suitable precursors, such as R 1 —OH is produced. As defined herein, R 1 —OH is exposed to protic and / or Lewis acids to give rise to the cation R 1 Acts as an electrophile to react with Al. In one embodiment, the cationic form of R 1 It is Ph2CH + .

[0113] The method comprises reacting a diimine compound with EX, wherein E is an electrophile. When the diimine compound reacts with E—X, X becomes the counterion of the compound of formula I as defined herein, and the electrophilic portion E reacts with the solvent or other components of the reaction mixture and is ultimately discarded. Suitable electrophilic E groups include, but are not limited to, alkyl silanes.

[0114] In various embodiments, the compound is a compound of Formula IV or a salt, solvate, geometric isomer or stereoisomer thereof,

[0115]

[0116] In the compound of Formula IV, X is as defined herein.

[0117] In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently optionally substituted C1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently optionally substituted C 1-12 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently optionally substituted OC 1-12 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently optionally substituted C 3-12 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently optionally substituted C 6-18 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently optionally substituted C 6-18 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently A1. In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently R 1 In certain embodiments, R A , R 5 or R 6 At least one occurrence of is independently R 2 In certain embodiments, R 5 and R 6The optional substitution is at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2、N(R)C(O)OR、C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl), C 1-12 Heteroalkyl, OC 1-12 Alkyl, C 3-12 Cycloalkyl, C 6-10 Aryl and C 6-10 Heteroaryl.

[0118] Deprotonation of the compound of formula IV results in the formation of a cyclic alkylaminocarbene (CAAC). The carbene derived from the compound of formula IV can form a metal complex of formula IVa:

[0119]

[0120] In the structure of Formula IVa, M, L and 'p' are as defined herein.

[0121] In various embodiments, the compound is a compound of Formula V or a salt, solvate, geometric isomer or stereoisomer thereof:

[0122]

[0123] In the compound of formula V, X, R 5 and R 6 As defined herein. 7 Definition and R 5 Same. Variable Y is either N or C, and Z is either N or C, provided that Y and Z cannot both be C. G does not exist or is defined in the same way as R. 5The compound of formula V is a mesoionic carbene precursor. Upon transmetallation, the compound of formula V can form a metal-carbene complex of formula Va:

[0124]

[0125] For example, a compound of formula V can undergo the following reaction to form a compound of formula Va:

[0126]

[0127] In the structure of Formula Va, M, L and 'p' are as defined herein.

[0128] In various embodiments, the compound is a mesoionic carbene precursor selected from:

[0129]

[0130] In certain embodiments, the optional substitution of any group considered herein includes halogen. In certain embodiments, the optional substitution of any group considered herein includes OR. In certain embodiments, the optional substitution of any group considered herein includes SiR3. In certain embodiments, the optional substitution of any group considered herein includes OSiR3. In certain embodiments, the optional substitution of any group considered herein includes OSiR3. In certain embodiments, the optional substitution of any group considered herein includes OSi(OR)3. In certain embodiments, the optional substitution of any group considered herein includes BR3. In certain embodiments, the optional substitution of any group considered herein includes BR2. In certain embodiments, the optional substitution of any group considered herein includes B(OR)3. In certain embodiments, the optional substitution of any group considered herein includes B(OR)2. In certain embodiments, the optional substitution of any group considered herein includes CN. In certain embodiments, the optional substitution of any group considered herein includes CF3. In certain embodiments, the optional substitution of any group considered herein includes OCF3. In certain embodiments, the optional substitution of any group considered herein includes SO2R. In certain embodiments, the optional substitution of any group considered herein includes SO2N(R)2. In certain embodiments, optional substitutions for any group contemplated herein include SO3R. In certain embodiments, optional substitutions for any group contemplated herein include C(O)R. In certain embodiments, optional substitutions for any group contemplated herein include NR2. In certain embodiments, optional substitutions for any group contemplated herein include N(R)SO2R. In certain embodiments, optional substitutions for any group contemplated herein include N(R)SO2N(R)2. In certain embodiments, optional substitutions for any group contemplated herein include (CH2)0-2 N(R)C(O)R. In certain embodiments, optional substitutions for any group contemplated herein include (CH2) 0-2 N(R)N(R)2. In certain embodiments, optional substituents for any group contemplated herein include N(R)C(O)OR. In certain embodiments, optional substituents for any group contemplated herein include C 1-12 Hydrocarbyl (such as, but not limited to, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 In certain embodiments, optional substitutions for any group contemplated herein include C 1-12 In certain embodiments, optional substitutions for any group contemplated herein include OC 1-12 In certain embodiments, optional substitutions for any group contemplated herein include C 3-12 In certain embodiments, optional substitutions for any group contemplated herein include C 6-10 In certain embodiments, optional substitutions for any group contemplated herein include C 6-10 Heteroaryl.

[0131] 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 include racemic, optically active, regioisomers, 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, as non-limiting examples, by resolving the racemic form with recrystallization techniques, synthesizing from optically active raw materials, chiral synthesis, or chromatographic separation using a chiral stationary phase. In certain embodiments, a mixture of one or more isomers is used 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 mixtures of enantiomers and / or diastereomers. The resolution of compounds and their isomers may be achieved by any means, including but not limited to chemical processes, enzymatic processes, fractional crystallization, distillation, and chromatography.

[0132] 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 compound (one or more) described herein, as well as metabolites and active metabolites of these compounds having the same active type. 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 solvated forms with pharmaceutically acceptable solvents such as water and ethanol. In other embodiments, the compounds described herein exist in non-solvated forms.

[0133] In certain embodiments, the compound(s) described herein may exist as tautomers. All tautomers are included within the scope of the compounds presented herein.

[0134] In certain embodiments, the compounds described herein are prepared as prodrugs. "Prodrug" refers to an agent that is converted into a parent drug in vivo. In certain embodiments, after in vivo administration, the prodrug is chemically converted into a biological, pharmaceutical or therapeutically active form of the compound. In other embodiments, the prodrug is enzymatically metabolized to a biological, pharmaceutical or therapeutically active form of the compound by one or more steps or processes.

[0135] In certain embodiments, sites on the aromatic ring portion of compounds described herein are susceptible to various metabolic reactions. Addition of appropriate substituents to the aromatic ring structure can reduce, minimize or eliminate such metabolic pathways. In certain embodiments, by way of example only, appropriate substituents that reduce or eliminate the sensitivity of the aromatic ring to metabolic reactions are deuterium, halogen or alkyl.

[0136] The compounds described herein also include isotopically labeled compounds in which 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 S. 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., increased in vivo half-life or reduced dosage requirements). In yet other embodiments, substitution with positron emitting isotopes such as 11 C. 18 F. 15 O and 13 N substitution is useful in positron emission topography (PET) studies for examining substrate receptor occupancy. Isotopically labeled compounds are prepared by any suitable method or process by using an appropriate isotopically labeled reagent in place of the unlabeled reagent otherwise employed.

[0137] 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.

[0138] The compounds described herein and other related compounds having various substituents are prepared using the methods described herein and, for example, in Fieser & Fieser's Reagents for Organic Synthesis, Vols. 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Vols. 1-5 and Supplements (Elsevier Science Publishers, 1989); Organic Reactions, Vols. 1-40 (John Wiley and Sons, 1991), Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989), March, Advanced Organic Chemistry, 4th Edition, (Wiley 1992); Carey & Sundberg, Advanced Organic Chemistry, 4th Edition, Vols. A and B (Plenum 2000, 2001) and Green & Wuts, Protective Groups in Organic Synthesis, 3rd Edition, (Wiley 1999) (all of which are incorporated into the present disclosure by reference). The general methods for preparing compounds as described herein are modified by using appropriate reagents and conditions to introduce the various moieties present in the formulae as provided herein.

[0139] The compounds described herein are synthesized using any suitable procedures starting from compounds available from commercial sources or prepared using the procedures described herein.

[0140] In some embodiments, reactive functional groups, such as hydroxyl, amino, imino, sulfenyl or carboxyl, are protected to avoid them from undesirably participating in reactions. Protective groups are used to block some or all of the reactive moieties, and prevent these groups from participating in chemical reactions until the protective group is removed. In other embodiments, each protective group can be removed by different means. The protective group cracked under completely different reaction conditions meets the requirement of difference removal.

[0141] In certain embodiments, the protecting group is removed by acid, base, reducing conditions (e.g., hydrogenolysis) and / or oxidizing conditions. Groups such as trityl, dimethoxytrityl, acetal, and tert-butyldimethylsilyl are acid-labile and are used to protect carboxyl and hydroxyl reactive moieties in the presence of amino groups protected by Cbz groups and base-labile Fmoc groups that can be removed by hydrogenolysis. Carboxylic acid and hydroxyl reactive moieties are blocked by base-labile groups (e.g., methyl, ethyl, and acetyl) in the presence of amines blocked by acid-labile groups (e.g., tert-butyl carbamate) or acid- and base-stable but hydrolyzable carbamates.

[0142] In certain embodiments, carboxylic acid and hydroxyl reactive moieties are blocked by hydrolytically removable protecting groups such as benzyl, while amine groups capable of forming hydrogen bonds with acids are blocked by base labile groups such as Fmoc. Carboxylic acid reactive moieties are protected by conversion to simple ester compounds exemplified herein, including conversion to alkyl esters or blocking with oxidatively removable protecting groups such as 2,4-dimethoxybenzyl, while coexisting amino groups are blocked with fluoride-labile silylcarbamates.

[0143] Allyl blocking groups are useful in the presence of acid and base protecting groups because the former are stable and subsequently removed by metal or π-acid catalysts. For example, in the presence of acid-labile tert-butyl carbamate or base-labile acetamine protecting groups, allyl-blocked carboxylic acids are deprotected using palladium-catalyzed reactions. Another form of protecting group is a resin connected to a compound or intermediate. As long as the residue is connected to the resin, the functional group will be blocked and will not react. Once released from the resin, the functional group can react.

[0144] Typically blocking / protecting groups may be selected from:

[0145]

[0146] Other protecting groups, as well as a detailed description of techniques suitable for the creation of protecting groups and their removal, are described in Greene & Wuts, Protective Groups in Organic Synthesis, 3rd Edition, John Wiley & Sons, New York, NY, 1999 and Kocienski, Protective Groups, Thieme Verlag, New York, NY, 1994, which are hereby incorporated by reference for such disclosures.

[0147] Example

[0148] Various embodiments of the present application can be better understood by referring to the following exemplary embodiments. The scope of the present application is not limited to the embodiments given herein.

[0149] The synthesis of compounds of Formula I, such as compound 5, also referred to herein as "IPr#", is shown in Scheme 1. It should be noted that direct triple alkylation of aniline is significantly more challenging than alkylation of para-blocked toluidine as a result of N- / C-alkyl migration. After experimentation, it was unexpectedly discovered that previously unknown 2,4,6-tribenzhydrylaniline 7 could be prepared in 79% yield (93 g, 200 mmol scale) by adding HCl (1.0 equiv) to a solution of aniline (1.0 equiv), benzhydrol (3.5 equiv) and ZnCl2 (0.5 equiv) at 160°C. Typically, yields of 70-75% were obtained on a 10-20 mmol scale. This represents a significant improvement over the previous Friedel-Crafts method, which involved adding a mixture of ZnCl2 and HCl at 160°C, which resulted in irreproducible results. Without being bound by theory, it is believed that alkylation of the aniline in the para position occurs last; no N-alkylated product was observed. The synthesis of diimine 8 proceeded smoothly by reacting glyoxal (1.0 equiv) with amine 7 (2.0 equiv) and MgSO4 (2.5 equiv) (70 g, 160 mmol scale). The reaction was slower than the synthesis of IPr*, indicating that the steric characteristics were more pronounced. The diimine was formed only as the s-trans isomer. When the diimine (1.0 equiv) and paraformaldehyde (1.1 equiv) were exposed to a solution of TMSCl (1.1 equiv) in EtOAc at 70°C (25 g, 40 mmol scale), the cyclization step proceeded smoothly. In some embodiments, this process allowed a milder cyclization to 5 than the HCl / ZnCl2 combination, which again proved to be problematic for large-scale operation and was full of retro-Friedel-Crafts products. The TMSCl process can be conveniently carried out with a color change from yellow to light gray, indicating that the reaction is complete.

[0150] Solution 1.IPr # Synthesis of diimine precursors a

[0151]

[0152] aConditions: (a) 6 (1.0 equiv), Ph2CHOH (3.5 equiv), ZnCl2 (0.5 equiv), HCl (36%, aq, 1.0 equiv), 160°C. (b) 7 (1.0 equiv), (CHO) 2 (40%, aq, 0.5 equiv), MgSO4 (2.5 equiv), 23°C. (c)8(1.0equiv), (CH2O) n (1.1 equiv), TMSCl (1.1 equiv), EtOH, 70°C.

[0153] In various embodiments, (1) these three steps do not require purification of intermediates, (2) the final product is obtained after simple work-up (filtration), (3) the process uses industrial chemicals that are available in large quantities, and (4) the sequence is typically performed within two days.

[0154] With multiple access to IPr# ensured, we next comprehensively evaluated the steric and electronic properties of this novel NHC ligand. As shown in Scheme 2, the gold complex [Au(IPr#)Cl] (9) was prepared using the general method published by Nolan, while the Rh(I) complexes [Rh(IPr#)(CO)2Cl] (10) and [Rh(IPr#)(acetoacetate)CO] (11) were prepared after in situ generation of free carbenes by deprotonation of IPr#HCl with a slight excess of KHMDS or KOt-Bu. The Rh(I) complex (10) can be prepared by directly using the dicarbonyl rhodium chloride dimer [{Rh(CO)2(μ-Cl)}2] (path b) or by a mild two-step process of [Rh(IPr#)(cod)Cl] and reaction with carbon monoxide (path c). In some embodiments, the selenium adduct [Se(IPr#)] (12) can be generated by adding the in situ generated free carbenes to an excess of selenium. The Pd(II) complex [Pd(IPr#)(cin)Cl] (13) was prepared by in situ generation of free carbenes and coordination with the cinnamyl palladium dimer [{Pd(cin)(μ-Cl)}2]. In various embodiments, all complexes are stable to air and moisture. Complexes 9 and 13 were fully characterized by X-ray crystallography ( Figure 2 and 3 ).

[0155] Solution 2.IPr # Synthesis of complexes a

[0156]

[0157] aConditions: (a) AuCl·Me2S (1.0 equiv), K2CO3 (6.0 equiv), acetone, 60°C, 2h, 90%. (b) KHMDS (1.8 equiv), [Rh(CO)2Cl]2 (0.5 equiv), toluene, 23°C, 15h, 88%. (c) [Rh(cod)Cl]2 (0.5 equiv), K2CO3 (2.0 equiv), acetone, 60°C, 8h, 71%, then CO, CH2Cl2, 23°C, 15h, 90%. (d) KOt-Bu (2.0 equiv), [Rh(acetoacetate)(CO)2] (1.0 equiv), THF, 23°C, 15h, 93%. (e) Se (3.0 equiv), NaHMDS (1.2 equiv), THF, -78 to 23°C, 15h, 95%. (f) KOt-Bu (1.1 equiv), [Pd (cin) Cl] 2 (0.45 equiv), THF, 23°C, 15h, 89%.

[0158] Some previous studies have shown that the % buried volume (% V bur ) and spatial mapping are the best metrics for quantifying the spatial impact of NHC ligands. In one embodiment, [Au(IPr#)Cl] is linear (C–Au–Cl, 180.0°; C–Au, ), making it evaluate %V bur Therefore, in (%V bur ) is 54.5%, [Au(IPr#)Cl] represents one of the most bulky NHC ligands prepared to date (Table 1). This value is comparable to that of [Au(IPr*)Cl] (C–Au–Cl, 178.3°; C–Au, ) determined (%V bur ) is 50.4% equivalent, indicating a small but significant effect of the p-benzhydryl substitution on the steric properties of the ligand. Figure 4 A graphical representation of the stereo mapping of the metal center in [Au(IPr#)Cl] is shown in FIG.

[0159] Table 1. Summary of stereo and electronic parameters

[0160]

[0161] a Methyl (Menthyl) replaces cyclohexyl. b Me2 replaces the cyclohexyl group.

[0162] Tolman electronic parameters (TEP) allow the electronic properties of NHC ligands to be evaluated. Thus, the CO stretching frequencies of [Rh(IPr#)(CO)2Cl] are v sym =2079.5cm -1 and v asym =1999.5cm -1 (CH2Cl2, 0.20M), which corresponds to 2051.8cm -1 The TEP of the ligand is a comprehensive measure of the electronic properties of the ligand. These values ​​are comparable to those of the IPr ligand (TEP of 2051.5 cm -1 )、IPr*(TEP is 2052.7cm -1 ) and CAAC Cy (TEP is 2048.6cm -1 ) matches well and indicates that the prepared supply is one of the most 5-membered NHCs.

[0163] Similarly, selenourea adducts can be used to assess 77 π-backbonding in Se NMR spectra. δ of [Se(IPr#)](CDCl3) Se The value is 108.11 ppm, which indicates that the π-accepting performance caused by the extended substitution is slightly higher than that of IPr (δ Se =90ppm) and IPr*(δ Se =106ppm) and is much lower than CAAC Me2 (δ Se =492 ppm), as expected for the C substitution.

[0164] In addition, from 1 H NMR spectroscopy 13 The single-bond CH J coupling constants obtained from the C satellite peaks are a good indication of the σ-donating properties of the NHC ligands. The 224.50 Hz value of IPr#HCl(CDCl3) is consistent with the affinity of this ligand to IPr( 1 J CH =223.70 Hz), but at the same time the steric requirements and flexibility are significantly higher. The chemical shift of the iminium proton in IPr#HCl was found to be 12.6 ppm (CDCl3), which is significantly downfield compared to other imidazolium salts.

[0165] The synthesis of [Rh(IPr#)(acetoacetate)CO] shows that the extremely bulky IPr# can accommodate the asymmetric k 2 -O,O binds to a ligand such as acetoacetate. In certain embodiments, this results in a steric adjustment of the ligand topology to fit within the Rh coordination plane.

[0166] This property was confirmed by the synthesis and complete crystallographic characterization of [Pd(IPr#)(cin)Cl]( Figure 3 Based on the elegant report of Nolan and Hazari, a Pd(II) allylic complex (13) was selected as a well-defined, air- and moisture-stable Pd(II)-NHC precatalyst to evaluate the performance of IPr# in the cross-coupling reaction. X-ray crystallographic analysis showed (% V bur ) is 44.7%, and each quadrant is 64.1%, 27.8%, 60.1%, 26.6% ( Figure 4 B in the figure). These values ​​can be compared with the linear [Au(IPr#)Cl] (%V bur )54.5% for comparison, and 56.3%, 52.6%, 56.3%, 52.6% for each quadrant respectively ( Figure 4 A in Figure 1). Thus, IPr# ligands are able to (1) modulate the steric environment and (2) asymmetric twists around the metal center, which is important for the catalytically differentiated quadrant distribution caused by the very bulky but flexible ligand topology. and The C–Pd, Pd–Cl, and Pd–C(Ph) bond lengths of Pd(II)-allylic complexes ([Pd(IPr)(cin)Cl], C–Pd, Pd–Cl, Pd–C(Ph), ) within the range of .

[0167] It is further noteworthy that the benzhydryl substituents at the IPr# wing tips extend beyond the metal center in both 9 and 13, which may affect (1) substrate approach and (2) coordination of the active intermediates formed during catalysis.

[0168] The activity of IPr# was evaluated in a variety of palladium-catalyzed cross-couplings (Scheme 3). As mentioned above, [Pd(IPr#)(cin)Cl] was chosen because of the success of well-defined Pd(II)-NHCs supported by allylic-type disposable ligands and the potential for tuning the catalyst activity through allylic modification. The results outlined in Scheme 3 demonstrate the versatility of IPr#. Thus, amide NC(O) Suzuki cross-coupling (entry 1), ester CO amidation (entry 2), amide NC(O) transamidation (entry 3), C–Cl Suzuki cross-coupling (entry 4), C–Cl Buchwald–Hartwig amination (entry 5), C–Br Feringa coupling using two aryls (entry 6) and a challenging alkyl lithium with a β-hydrogen (entry 7), C–Cl ketone α-arylation (entry 8), CS sulfur metathesis (entry 9), and CH activation (entry 10) all proceeded in good to excellent yields. More importantly, these results demonstrate that IPr# ligands are effective in a range of NC, OC, C-Cl, C-Br, C-S, and C-H bond cross-couplings with various organometallics (B, Li, enolates, amines, sulfides), some of the most widely used cross-couplings in industrial and academic settings.

[0169] The generality of the IPr# ligand design concept and two further applications are presented in Scheme 4. In various embodiments, compounds of Formula I such as BIAN-IPr# (14) and Np# (15) demonstrate the synthetic potential of the "hash" modular framework described herein. Thus, BIAN (BIAN = bis(imino)acenaphthene) ligands have emerged as powerful ligands in catalysis due to the structural rigidity of the CH bond, allowing the wing-tip substituents to be closer to the metal center and redox activity, as well as the more pronounced σ-donating properties of the carbene center. The synthesis of BIAN-IPr# (14) proceeded smoothly with access to 2,4,6-tris(diphenylmethyl)aniline 7, easily providing 1.5 g of 14 using acenaphthenequinone (16) as the NHC precursor.

[0170] Similarly, C2-symmetric imidazolin-2-ylene groups bearing substituted naphthyl chains reported by Dorta have become the most active NHC auxiliary ligands in Pd-catalyzed cross-coupling and Ru-metathesis. However, the synthesis of 2,7-substituted naphthyl wingtips has been a limitation.

[0171] Scheme 3. [Pd(IPr # Activity of )(cin)Cl]13 in cross-coupling reactions a

[0172]

[0173] Solution 4.IPr# NHC: (a) BIAN-IPr # and (b) Np # Generalization

[0174]

[0175] Table 2. HOMO and LUMO energy levels (eV) of IPr# calculated at the B3LYP 6-311++g(d,p) level

[0176]

[0177] a Racemic-Np#(C2-symmetric). Meso-Np#(C S -symmetric), -5.97eV and -1.57eV. Calculated at the B3LYP6-311++g(d,p) level, racemic-Np# is more stable than meso-Np# by 0.56kcal / mol.

[0178] Applying the concepts described herein, the synthesis of Np# (15), which exploits the facile synthesis of 2,4,7-tris(diphenylmethyl)naphthalene-1-amine (17) via Friedel-Crafts alkylation, proceeded smoothly and provided 2.5 g of this spatially differentiated NHC ligand. Thus, the use of the "hashing" concept allows for modular, rapid, and cost-effective ligand assembly that is potentially applicable to (1) a wide variety of carbenes and (2) a wide variety of amines (see Np#).

[0179] To further evaluate the effect of substitution on the electronic properties of 5, the HOMO and LUMO energy levels of IPr# and classical NHC were determined at the B3LYP 6-311++g(d,p) level of theory (Table 2). Calculation of HOMO and LUMO can most accurately estimate the nucleophilicity (more σ-donating, higher HOMO) and electrophilicity (more π-accepting, lower LUMO) of NHC, however, the values ​​used for comparison must be available at the same level of theory.

[0180] The HOMO of IPr# (-6.16 eV) is comparable to that of IPr (-6.01 eV), a conventional model for σ-donating NHCs. Substitution of the N-phenyl ring with an N-naphthyl group renders Np# nucleophilic similar to classical NHCs (HOMO, -6.04 eV) but with enhanced electrophilicity (LUMO, -1.55 eV). It is therefore clear that, in combination with different steric influences, the IPr# ligand class is well suited for electronic fine-tuning of its homogeneous catalytic properties.

[0181] The terms and expressions used herein are used as descriptive terms rather than limiting terms, and when using these terms and expressions, it is not intended to exclude any equivalents of the features shown and described or parts thereof, but it should be recognized that various modifications within the scope of the embodiments of the present application are possible. Therefore, it should be understood that although the present application describes specific embodiments and optional features, modifications and changes to the compositions, methods and concepts disclosed herein may be adopted by those of ordinary skill in the art, and such modifications and changes are considered to be within the scope of the embodiments of the present application.

[0182] Examples of implementation methods

[0183] The following exemplary embodiments are provided, the numbering of which should not be construed as designating a degree of importance:

[0184] Embodiment 1 provides a compound of formula I or a salt, solvate, geometric isomer or stereoisomer thereof:

[0185]

[0186] in: is a single bond or a double bond; A1 and A2 are each independently C 6-18 Aryl or C 6-18 Heteroaryl; R 1 and R 2 are each independently C substituted by at least one aryl or heteroaryl 1-3 Alkyl, where R 1 and R 2 The aryl or heteroaryl in the formula (a) is optionally substituted by at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12heteroaryl and optionally substituted C 1-12 Acyl; R 3 and R 4 are each independently hydrogen, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12 Acyl, wherein the optional substitution independently comprises at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 Acyl; or R 3 and R 4 Together with the rings to which they are attached, they form C 4-20 Cycloalkyl, C 6-20 Aryl or C 6-20 Heteroaryl, each of which is independently optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2)0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 acyl; X is a counter anion; R is independently hydrogen at each occurrence, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl or optionally substituted C 1-10 acyl; k is 1, 2, 3 or 4; m is an integer from 0 to 6; n is an integer from 0 to 6; and provided that if A1 and A2 are phenyl, at least one of m or n is 3, 4 or 5.

[0187] Embodiment 2 provides compounds of embodiment 1, wherein A1 and A2 are the same.

[0188] Embodiment 3 provides a compound of any one of embodiments 1-2, wherein A1 is C 6-10 Aryl.

[0189] Embodiment 4 provides a compound of any one of embodiments 1-3, wherein A1 is phenyl.

[0190] Embodiment 5 provides a compound of any one of embodiments 1-3, wherein A1 is naphthyl.

[0191] Embodiment 6 provides compounds of any of embodiments 1-5, wherein at least one of the following applies: m is 3, n is 3 or k is 1.

[0192] Embodiment 7 provides a compound of any one of embodiments 1-6, wherein the compound is selected from

[0193]

[0194]

[0195] Where R 1 Selected from CH(phenyl)2, CH(4-Me-C6H4), CH(4-t-Bu-C6H4)2, CH(4-MeO-C6H4)2, CH(4-CF3-C6H4)2, CH(3,5-dimethyl-C6H3)2, CH(3,5-bis(trifluoromethyl)-C6H3)2 and CH(3,5-difluoro-C6H3)2.

[0196] Embodiment 8 provides compounds of any one of embodiments 1-7, wherein X is Cl.

[0197] Embodiment 9 provides a compound of any one of embodiments 1-8, wherein R 1 and R 2 are the same.

[0198] Embodiment 10 provides a compound of any one of embodiments 1-9, wherein R 1 It is CH(aryl)2.

[0199] Embodiment 11 provides a compound of any one of embodiments 1-10, wherein R 1 It is CH(phenyl)2.

[0200] Embodiment 12 provides a compound of any one of embodiments 1-11, wherein m is 3 and n is 3.

[0201] Embodiment 13 provides a compound of any one of embodiments 1-12, wherein X is selected from F, Cl, Br, I, OSO2R, OSO3R, and OC(=O)R.

[0202] Embodiment 14 provides a compound of any one of embodiments 1-13, wherein X is Cl.

[0203] Embodiment 15 provides a compound of formula II or a salt, solvate, geometric isomer or stereoisomer thereof:

[0204]

[0205] wherein: M is an element of Group VIII to Group XVI, whose atomic weight is greater than 25; L is a ligand of M, wherein L may be the same or different at each occurrence; p is an integer from 0 to 5; and is a single bond or a double bond; A1 and A2 are each independently C 6-10 Aryl or C 6-10 Heteroaryl; R 1 and R 2 are each independently C substituted by at least one aryl or heteroaryl 1-3 Alkyl, where R 1 and R 2 The aryl or heteroaryl in the formula (a) is optionally substituted by at least one group selected from the following: halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 Acyl; R 3 and R 4 are each independently hydrogen, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl or optionally substituted C 1-12Acyl, wherein the optional substitution independently comprises at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 Acyl; or R 3 and R 4 Together with the rings to which they are attached, they form C 4-20 Cycloalkyl, C 6-20 Aryl or C 6-20 Heteroaryl, each of which is independently optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12acyl; R at each occurrence is independently hydrogen, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl or optionally substituted C 1-10 acyl; k is 1, 2, 3 or 4; m is an integer from 0 to 5; n is an integer from 0 to 5; and provided that if A1 and A2 are phenyl, at least one of m or n is 3, 4 or 5.

[0206] Embodiment 16 provides compounds of embodiment 15, wherein M is selected from Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag, Re, Os, Ir, Pt and Au.

[0207] Embodiment 17 provides a compound of any one of embodiments 15-16, wherein M is a Group XVI element.

[0208] Embodiment 18 provides compounds of any one of embodiments 15-17, wherein p is 0, 1 or 2.

[0209] Embodiment 19 provides compounds of any of embodiments 15-18, wherein at least one L is an anionic ligand.

[0210] Embodiment 20 provides a compound of any one of embodiments 15-19, wherein at least one L is a neutral ligand.

[0211] Embodiment 21 provides a compound of any one of embodiments 15-20, wherein at least one L is selected from acetoacetic acid, Cl, 3-Cl-pyridine, pyridine, N-R'-imidazole, cinnamyl, allyl, 1-R"-indenyl, Cp (cyclopentadienyl), aniline, 3-CF3-aniline, μ-Cl, μ-OH, 1,4-naphthoquinone, CpCl, PR A 3. di-tert-butyl fumarate and methyl methacrylate; wherein R' is Me, Et, Bu or Ph; R" is t-Bu, i-Pr, Et, Me, cyclohexyl or 1-adamantyl; and PR A 3, where each R A is independently optionally substituted C 1-8 Alkyl, optionally substituted C 2-8Alkenyl, optionally substituted C 2-8 Alkynyl, optionally substituted C 3-8 Cycloalkyl, optionally substituted C 1-8 Heteroalkyl, optionally substituted C 1-8 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl or optionally substituted C 1-12 Acyl.

[0212] Embodiment 22 provides a compound of any one of embodiments 15-21, wherein the compound is selected from [Pd(NHC)(acetoacetate)Cl], [Pd(NHC)(3-Cl-pyridine)Cl2], [Pd(NHC)(pyridine)Cl2], [Pd(NHC)(N-R'-imidazole)Cl2], [Pd(NHC)(cinnamyl)Cl], [Pd(NHC)(allyl)Cl], [Pd(NHC)(1-R"-indenyl)Cl] (R=), [Pd(NHC)(Cp)Cl] (Cp=cyclopentadienyl), [Pd(NHC)(aniline)Cl2]), [Pd(NHC)(3-CF3-aniline)Cl2], [Pd(NHC)(μ-Cl)Cl]2, [Pd(NHC)(μ-OH)Cl]2, [Pd(NHC)(1,4-naphthoquinone)], [Ni(NHC)CpCl], [Ni(NHC)(PR A 3)X A 2], [Ni(NHC)(di-tert-butyl fumarate)2], [Ni(NHC)(methyl methacrylate)2], [Au(NHC)X B ], [Cu(NHC)X A ]、[Ag(NHC)X A ]、

[0213] Wherein NHC is selected from:

[0214]

[0215] R 1 Selected from CH(phenyl)2, CH(4-Me-C6H4), CH(4-t-Bu-C6H4)2, CH(4-MeO-C6H4)2, CH(4-CF3-C6H4)2, CH(3,5-dimethyl-C6H3)2, CH(3,5-bis(trifluoromethyl)-C6H3)2 and CH(3,5-difluoro-C6H3)2;

[0216] R' is Me, Et, Bu or Ph;

[0217] R" is t-Bu, i-Pr, Et, Me, cyclohexyl or 1-adamantyl;

[0218] PR A 3, where each R A is independently optionally substituted C 1-8 Alkyl, optionally substituted C 2-8 Alkenyl, optionally substituted C 2-8 Alkynyl, optionally substituted C 3-8 Cycloalkyl, optionally substituted C 1-8 Heteroalkyl, optionally substituted C 1-8 Alkoxy, optionally substituted C 6-10 aryl, optionally substituted C2-C8 heterocyclyl, optionally substituted C4-C8 heteroaryl or optionally substituted C 1-12 acyl group;

[0219] X is Cl or Br;

[0220] X A is Cl, Br, or I; and

[0221] X B is Cl, Br, I, NTf2 or OTf.

[0222] Embodiment 23 provides a method for preparing a compound of any one of embodiments 2-14, the method comprising: making a compound having the structure Compounds with cationic forms of R 1 contacting to form a compound of Formula III or a salt, solvate, geometric isomer or stereoisomer thereof: The compound of formula III is condensed with (CHO)2 to form a compound having the structure A diimine compound or a salt, solvate, geometric isomer or stereoisomer thereof; and cyclizing the diimine compound to form the compound of formula I or a salt, solvate, geometric isomer or stereoisomer thereof.

[0223] Embodiment 24 provides the method of embodiment 23, wherein the cationic form of R 1 It is Ph2CH + .

[0224] Embodiment 25 provides the method of any one of embodiments 23-24, wherein the cyclization comprises reacting the diimine compound with E—X, wherein E is an electrophile.

[0225] Embodiment 26 provides a compound of formula IV or a salt, solvate, geometric isomer or stereoisomer thereof: Where: R A , R 5 and R 6 independently selected from optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-18 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 18 Heteroaryl, optionally substituted C 1-12 acyl and C substituted with at least one aryl or heteroaryl 1-3 Alkyl, wherein the optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 acyl; X is a counter anion; and R is independently hydrogen at each occurrence, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C10 heteroaryl or optionally substituted C 1-10 Acyl.

[0226] Embodiment 25 provides a compound of formula IVa or a salt, solvate, geometric isomer or stereoisomer thereof: Where: R A , R 5 and R 6 are independently selected from optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C1- 12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-18 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 18 Heteroaryl, optionally substituted C 1-12 acyl and C substituted with at least one aryl or heteroaryl 1-3 Alkyl, wherein the optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 acyl; M is an element from Group VIII to Group XVI having an atomic weight greater than 25; L is a ligand of M, wherein L may be the same or different at each occurrence; p is an integer from 0 to 5; and R is independently hydrogen, optionally substituted C 1-10 Alkyl, optionally substituted C2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl, optionally substituted C4-C 10 heteroaryl and optionally substituted C 1-10 Acyl.

[0227] Embodiment 27 provides a compound of Formula V or a salt, solvate, geometric isomer or stereoisomer thereof: Among them: Each R 5 , R 6 and R 7 independently selected from optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-18 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 18 Heteroaryl, optionally substituted C 1-12 acyl and C substituted with at least one aryl or heteroaryl 1-3 Alkyl, wherein the optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 acyl; X is a counter anion; Y is N or C; Z is N or C; G is absent, optionally substituted C1- 12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-18 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 18 Heteroaryl, optionally substituted C 1-12 acyl and C substituted with at least one aryl or heteroaryl 1-3 Alkyl, wherein the optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 Acyl; R at each occurrence is independently hydrogen or C 1-10 Hydrocarbyl, provided that Y and Z are not both C.

[0228] Embodiment 28 provides a compound of formula Va or a salt, solvate, geometric isomer or stereoisomer thereof: Among them: Each R 5 , R 6 and R 7 are independently selected from optionally substituted C1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-18 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 18 Heteroaryl, optionally substituted C 1-12 acyl and C substituted with at least one aryl or heteroaryl 1-3 Alkyl, optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R,(CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 acyl; Y is N or C; Z is N or C; M is an element from Group VIII to Group XVI, whose atomic weight is greater than 25; L is a ligand of M, wherein L may be the same or different at each occurrence; p is an integer from 0 to 5; and G is absent, optionally substituted, C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-18 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 18Heteroaryl, optionally substituted C 1-12 acyl and C substituted with at least one aryl or heteroaryl 1-3 Alkyl, wherein the optionally substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl, optionally substituted C4-C 12 heteroaryl and optionally substituted C 1-12 Acyl; R at each occurrence is independently hydrogen or C 1-10 Hydrocarbyl, provided that Y and Z are not both C.

Claims

1. A compound of formula II, or a salt thereof: in: M is Pd; L is a ligand of M, wherein L may be the same or different at each occurrence, and wherein each L is selected from acetoacetate, Cl, 3-Cl-pyridine, pyridine, N-R'-imidazole, cinnamyl, allyl, 1-R"-indenyl, cyclopentadienyl, 1,4-naphthoquinone, CpCl, di-tert-butyl fumarate, methyl methacrylate, and PR A 3; p is 2 or 3; and It is a double bond; A1 and A2 are each independently phenyl or naphthyl; R' is Me, Et, Bu or Ph; R" is t-Bu, i-Pr, Et, Me, cyclohexyl or 1-adamantyl; Each R A is independently optionally substituted C 1-8 Alkyl, optionally substituted C 2-8 Alkenyl, optionally substituted C 2-8 Alkynyl, optionally substituted C 3-8 Cycloalkyl, optionally substituted C 1-8 Heteroalkyl, optionally substituted C 1-8 Alkoxy, optionally substituted C 6-10 Aryl or optionally substituted C4-C8 heteroaryl; R 1 and R 2 Each independently represents CH(phenyl)2, wherein R 1 and R 2 The phenyl groups in the above mentioned groups are independently substituted by at least one group selected from the group consisting of halogen, OR, SiR3, OSiR3, OSi(OR)3, BR3, BR2, B(OR)3, B(OR)2, CN, CF3, OCF3, SO2R, SO2N(R)2, SO3R, C(O)R, NR2, N(R)SO2R, N(R)SO2N(R)2, (CH2) 0-2 N(R)C(O)R, (CH2) 0-2 N(R)N(R)2, N(R)C(O)OR, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 heterocyclic group and optionally substituted C 1-12 acyl group; R 3 and R 4 are each independently hydrogen, optionally substituted C 1-12 Alkyl, optionally substituted C 2-12 Alkenyl, optionally substituted C 2-12 Alkynyl, optionally substituted C 3-12 Cycloalkyl, optionally substituted C 1-12 Heteroalkyl, optionally substituted C 1-12 Alkoxy, optionally substituted C 6-12 Aryl, optionally substituted C2-C 12 Heterocyclyl or optionally substituted C 1-12 acyl group; R is independently, at each occurrence, hydrogen, optionally substituted C 1-10 Alkyl, optionally substituted C 2-10 Alkenyl, optionally substituted C 2-10 Alkynyl, optionally substituted C 3-10 Cycloalkyl, optionally substituted C 1-10 Heteroalkyl, optionally substituted C 1-10 Alkoxy, optionally substituted C 6-10 Aryl, optionally substituted C2-C 10 Heterocyclyl or optionally substituted C 1-10 acyl group; wherein the optional substitution comprises at least one group selected from the following: halogen, CN, CF3, OCF3, C 1-12 Alkyl, C 2-12 Alkenyl, C 2-12 Alkynyl, C 3-12 Cycloalkyl, C 1-12 Heteroalkyl, C 1-12 Alkoxy, C 6-12 Aryl, C2-C 12 Heterocyclic and C 1-12 acyl group; k is 1; m is 3, 4, or 5; and n is 3, 4, or 5.

2. The compound according to claim 1, wherein at least one L is an anionic ligand.

3. The compound of claim 1, wherein at least one L is a neutral ligand.

4. A compound, wherein the compound is selected from [Pd(NHC)(acetoacetate)Cl], [Pd(NHC)(3-Cl-pyridine)Cl2], [Pd(NHC)(pyridine)Cl2], [Pd(NHC)(N-R'-imidazole)Cl2], [Pd(NHC)(cinnamyl)Cl], [Pd(NHC)(allyl)Cl], [Pd(NHC)(1-R"-indenyl)Cl] and [Pd(NHC)(Cp)Cl]; Wherein NHC is selected from: R 1 Selected from CH(phenyl)2, CH(4-Me-C6H4)2, CH(4-t-Bu-C6H4)2, CH(4-MeO-C6H4)2, CH(4-CF3-C6H4)2, CH(3,5-dimethyl-C6H3)2, CH(3,5-bis(trifluoromethyl)-C6H3)2 and CH(3,5-difluoro-C6H3)2.

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