N-heterocyclic carbene transition metal compounds and their application in catalysis

Abstract

Provided is a new class of ionic N-heterocyclic carbene (NHC) transition metal compounds, which can be prepared by easily scalable synthetic routes with excellent yields and purities. The ionic NHC-transition metal compounds show high catalytic activity and high reaction efficiency in various transition metal-catalyzed reactions. There are further provided facile and scalable processes for synthesizing said ion c NHC-transition metal compounds and there are provided methods for performing transition metal-catalyzed reactions using said ionic NHC-transition metal compounds as precatalysts.

Description

N-HETEROCYCLIC CARBENE TRANSITION METAL COMPOUNDS AND THEIR APPLICATION IN CATALYSISField of the Invention

[0001] Provided is a new class of ionic N-heterocyclic carbene (NHC) transition metal compounds, which can be used as precatalysts for transition metal-mediated organic reactions. Various NHC motifs can be incorporated into such new class of ionic compounds following an easily scalable and facile synthetic routes starting from readily available substrates in a broad range of solvents with a simple workup, and excellent yields and purities. The ionic NHC transition metal compounds are low in cost and contain no organic auxiliary group. All ionic NHC transition metal compounds obtained were fully characterized using modem analytical methods such as, for example, NMR, elemental analyses, and single crystal X-ray analysis.

[0002] The ionic NHC-transition metal compounds according to the present invention can be used as precatalysts in various transition metal-mediated organic reactions, where they show high catalytic activity and high reaction efficiency.

[0003] For example, ionic NHC-Pd complexes can be used as precatalysts in i) C(sp2)-C(sp2) cross coupling reactions (e.g. Suzuki-Miyaura reaction), ii) C(sp2)-N coupling reactions (e.g. Buchwald-Hartwig amination reaction), iii) C(sp2)-0 coupling reactions, iv) C(sp2)-S coupling reactions, v) C(sp2)-P coupling reactions, and vi) ester / amide trans-amidation reactions (see Figure 1) with similar or better yields in comparison to commercially available state-of-the-art NHC-Pd precatalysts such as, for example, PEPPSI-IPr, etc.

[0004] The NHC-Pd precatalysts according to the present invention prevent the loss of precious metals during catalyst formation and are therefore more sustainable in comparison to conventional prior art precatalysts as mentioned above.

[0005] There are further provided facile and scalable processes for synthesizing said new ionic NHC-transition metal compounds starting from readily available substrates in a broad range of solvents with a simple workup, and excellent yields and purities.

[0006] Finally, there are provided methods for performing transition metal-catalyzed reactions between a first substrate and a second substrate using said ionic NHC-transition metal compounds as precatalysts, wherein said transition metal-catalyzed reactions are preferablyselected from C(sp2)-C(sp2) coupling reactions, C(sp2)-N coupling reactions, C(sp2)-0 coupling reactions, C(sp2)-S coupling reactions, C(sp2)-P coupling reactions or ester / amide trans-amidation reactions (see Figure 1), more preferably from Suzuki-Miyaura cross -coupling reactions, Buchwald-Hartwig amination reactions or ester / amide / / Y / / 7.s-amidation reactions (see Figure 2).Background of the Invention

[0007] Ligand-enabled Pd-catalyzed cross-coupling reactions are one of the most important reaction classes in modem chemistry [1], where LiPd(O) is commonly considered to be the active catalytic species in the cycle [2]. However, due to the instability of these catalytically active LiPd(O) species, they are usually preferred to be generated in situ.

[0008] In the early stages, formation of the catalytically active LiPd(0) species is achieved by target ligand displacement with either a stable Pd(0) precursor (such as Pdildbaja and Pd(PPh3)4) or in situ reduction of a Pd(II) complex with reductant (such as phosphine). Although straightforward, the former approach releases free dba or PPh? into the reaction system which may act as non-innocent spectators, and the latter consumes valuable phosphine ligands. Additionally, the generation of the not well-defined ligated Pd(0) species may even complicate further mechanistic investigations. To ease the situation, air-stable and well-defined Pd(II) precatalysts are developed. The catalytically active LiPd(0) is generated after activations, providing high catalytic efficiency in a wide range of cross -coupling reactions.

[0009] N-Heterocyclic carbene (NHC) has shown its uniqueness in different types of Pd or Ni-catalyzed cross -coupling reactions [3]. Specifically, for air-stable and well-defined NHC- Pd(II) precatalysts, current developments can be classified into two categories based on the auxiliary groups. The first class comes with an r|3-allyl group as the auxiliary component, which can easily undergo reductive elimination reaction in the presence of a base or a nucleophile to generate a Pd(0) complex. However, the comproportionation side reaction has been identified especially with a less sterically bulky r|3-allyl group, which overall would significantly reduce the actual catalyst concentration [4].

[0010] To tackle this problem, sterically hindered r|3-allyl group such as r|3-tBu-indenyl was developed with high efficiency in challenging cross -coupling reactions [5]. The latest report in this area is from GooBen where the methylnaphthyl anchored NHC-palladium system can outperform all the previous catalysts [6]. The second category is PEPPSLIPr precatalysts, whichcontaining a nitrogen-based L-type ligand, such as pyridine or aniline, to stabilize the complex [7]. The activation of such precatalysts usually follows the L-type ligand dissociation and reductive elimination steps to generate the active catalyst. These two precatalyst classes, although showing high reaction efficiency, suffer from the high-cost for scale up syntheses and the contamination of the auxiliary groups during the reaction.

[0011] Various NHC ligands and NHC complexes for transition metal catalysis are known from the state of the art [8]. However, the NHC-transition metal complexes shown here are nonionic. Basically the same applies to NHC-Pd precatalysts for cross-coupling reactions and their synthetic routes reported by Nolan et al. [9].

[0012] Asymmetrically substituted NHC palladates were reported as tunable aryl alkyl ionic liquids by Strassner et al

[0010] .

[0013] Nolan et al. reported on the role of NHCs in gold catalysis

[0011] and Santoro et al. reported on the synthesis, characterization and catalytic activity of stable [(NHC)H][ZnXY2] (NHC = N-heterocyclic carbene; X, Y = Cl, Br) species

[0012] .

[0014] Herein, we introduce another class of well-defined ionic NHC-transition metal compounds that are low in cost, contain no organic auxiliary group, and are accessible by easily scalable and facile synthetic routes starting from readily available substrates in a broad range of solvents with a simple workup, and excellent yields and purities.

[0015] The ionic NHC-transition metal compounds can be used as precatalysts in various transition metal-mediated organic reactions, exhibit high catalytic activity and high reaction efficiency, and prevent the loss of precious metals during catalyst formation, making them more sustainable compared to conventional prior art precatalysts.Summary of the Invention

[0016] Provided are new ionic N-heterocyclic carbene (NHC) transition metal compounds, which contain one or more NHC cations and one or more transition metal halide anions. There are further provided facile and scalable processes for synthesizing said ionic NHC-transition metal compounds and there are provided methods for performing transition metal-catalyzed reactions between a first substrate and a second substrate using said ionic NHC-transition metal compounds as precatalysts.

[0017] Hence, in a first embodiment of the present invention, there is provided a compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, wherein the N-heterocyclic carbene cation is:wherein:= represents a single bond or a double bond;Z represents a group selected fromwherein:R1is Cth-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andrepresents a binding site; and wherein the transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms; with the proviso that the following compounds are excluded:

[0018] In a second embodiment of the present invention, there is provided a compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, wherein the N-heterocyclic carbene cation is:wherein:= represents a single bond or a double bond;Z represents a group selected fromwherein:R1is CH3-yRy, wherein R is C2-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C2-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andwherein the transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms.

[0019] In a third embodiment, there is provided a process for synthesizing a compound according to the first embodiment or second embodiment, wherein the process comprises a step of reacting a N-heterocyclic carbene salt with a transition metal halide salt.

[0020] In a fourth embodiment of the present invention, there is provided a process for synthesizing a compound according to Formula I, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula A; and(ii) reacting said solution provided in step (i) with M2MxX4 to obtain a compound according to Formula I:Formula A Formula I wherein:= represents a single bond or a double bond;Z representswherein:R1is CH3-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M1is Pd; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0021] In a fifth embodiment of the present invention, there is provided a process for synthesizing a compound according to Formula II, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula B; and(ii) reacting said solution provided in step (i) with MIM2X4 or M2X2 to obtain a compound according to Formula II:Formula B Formula II wherein:= represents a single bond or a double bond;Z representswherein:R1is CHa-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M2is Pt or Zn, preferably Pt; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0022] In a sixth embodiment of the present invention, there is provided a process for synthesizing a compound according to Formula III, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula C; and(ii) reacting said solution provided in step (i) with MM3X4 to obtain a compound according to Formula III:Formula C Formula III wherein:= represents a single bond or a double bond;Z representswherein:R1is CFF-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0023] In a seventh embodiment of the present invention, there is provided a method for performing a transition metal-catalyzed reaction between a first substrate and a second substrate, wherein the method comprises the following steps:(a) providing a compound according to the first embodiment or second embodiment of the present invention as a precatalyst in a reaction vessel;(b) adding a first substrate and a second substrate to the reaction vessel; and(c) reacting the first substrate and the second substrate at a temperature and a time sufficient to perform a transition metal-catalyzed reaction.Brief Description of the Figures

[0024] Figure 1 shows non-limiting examples of i) C(sp2)-C(sp2) cross coupling reactions (e.g. Suzuki-Miyaura reaction), ii) C(sp2)-N coupling reactions (e.g. Buchwald-Hartwig amination reaction), iii) C(sp2)-0 coupling reactions, iv) C(sp2)-S coupling reactions, v) C(sp2)-P coupling reactions, and vi) ester / amide trans-amidation reactions.

[0025] Figure 2 shows non-limiting examples of the following transition metal-catalyzed reactions: a) Suzuki-Miyaura cross-coupling reaction, b) Buchwald-Hartwig amination reaction, and c) ester / amide trans-amidation reaction.Detailed Description

[0026] The compounds, the processes for synthesizing said compounds and the methods for performing transition metal-catalyzed reactions according to the present invention solve the problems known in catalysis and offer a powerful new platform to improve the yields of previously challenging cross-coupling reactions and at the same time reduce the loss of precious metal during catalyst formation and thus contribute to an improved sustainability.

[0027] The compounds according to the present invention are easy to synthesize and easy to scale up, low in cost and do not have any organic auxiliary group. They provide high reaction efficiency in transition metal-catalyzed reactions including, but not limited to Suzuki-Miyaura cross-coupling reactions, Buchwald-Hartwig amination reactions and ester / amide trans- amidation reactions. See Figure 2 for non-limiting examples of the reactions mentioned.

[0028] In the first embodiment of the present invention, there is provided a compoundcomprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, wherein the N-heterocyclic carbene cation is:wherein:= represents a single bond or a double bond;Z represents a group selected fromwherein:R1is CH3-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site; and wherein the transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms; with the proviso that the following compounds are excluded:

[0029] It is preferred in the first embodiment that R1is CFF-yRy, wherein R is C1-C10 alkyl or C6-Cio aryl, and y is 1, 2 or 3, preferably 2; and R2is H, C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1. It is more preferred in the first embodiment that R1is CFF-yRy, wherein R is methyl, ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; and R2is H, methyl, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i-propoxy, phenyl, phenyloxy or R1.

[0030] It is preferred in the first embodiment that the transition metal atom is selected from groups 10, 11 and 12 of the periodic table, preferably from the group consisting of Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd and Hg, more preferably from the group consisting of Pd, Pt, Au and Zn.

[0031] It is preferred in the first embodiment that the halogen atom is selected from the group consisting of F, Cl, Br and I, more preferably from the group consisting of C1 and Br, most preferably the halogen atom is Cl.

[0032] Preferably, in the first embodiment the transition metal atom is selected from groups 10, 11 and 12 of the periodic table and the halogen atom is selected from the group consistingof F, Cl, Br and I. More preferably, in the first embodiment the transition metal atom is selected from the group consisting of Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd and Hg and the halogen atom is selected from the group consisting of C1 and Br. Most preferably, in the first embodiment the transition metal atom is selected from the group consisting of Pd, Pt, Au and Zn and the halogen atom is Cl.

[0033] In the second embodiment of the present invention, there is provided a compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, wherein the N-heterocyclic carbene cation is:wherein:= represents a single bond or a double bond;Z represents a group selected fromwherein:R1is CH3-yRy, wherein R is C2-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C2-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andrepresents a binding site; and wherein the transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms.

[0034] It is preferred in the second embodiment that R1is CHa-yRy, wherein R is C2-C10 alkyl or C6-C10 aryl, and y is 1, 2 or 3, preferably 2; and R2is H, C2-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1. It is more preferred in the second embodiment that R1is CHa-yRy, wherein R is ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; and R2is H, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i-propoxy, phenyl, phenyloxy or R1.

[0035] It is preferred in the second embodiment that the transition metal atom is selected from groups 10, 11 and 12 of the periodic table, preferably from the group consisting of Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd and Hg, more preferably from the group consisting of Pd, Pt, Au and Zn.

[0036] It is preferred in the second embodiment that the halogen atom is selected from the group consisting of F, Cl, Br and I, more preferably from the group consisting of C1 and Br, most preferably the halogen atom is Cl.

[0037] Preferably, in the second embodiment the transition metal atom is selected from groups 10, 11 and 12 of the periodic table and the halogen atom is selected from the group consisting of F, Cl, Br and I. More preferably, in the second embodiment the transition metal atom is selected from the group consisting of Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd and Hg and the halogen atom is selected from the group consisting of C1 and Br. Most preferably, in the second embodiment the transition metal atom is selected from the group consisting of Pd, Pt, Au and Zn and the halogen atom is Cl.

[0038] It is preferred in the first embodiment and second embodiment that the transition metal halide anion is selected from the group consisting of:wherein:M1is Pd;M2is Pt or Zn, preferably Pt;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0039] It is more preferred in the first embodiment and second embodiment that the transition metal halide anion iswherein:M1is Pd; andX is halogen, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0040] As an alternative, it is more preferred in the first embodiment and second embodiment that the transition metal halide anion iswherein:M2is Pt or Zn, preferably Pt; andX is halogen, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0041] As a further alternative, it is more preferred in the first embodiment and second embodiment that the transition metal halide anion iswherein:M3is Au; andX is halogen, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0042] In a preferred embodiment of the present invention, the compound according to the first embodiment and second embodiment is represented by one of Formula I, Formula II or Formula III:Formula Iormula IIormula III wherein:M1is Pd;M2is Pt or Zn, preferably Pt;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl; and= and Z are defined as in the first embodiment or second embodiment.

[0043] In a more preferred embodiment of the present invention, the compound according to the first embodiment and second embodiment is represented by Formula I.

[0044] In an alternative more preferred embodiment of the present invention, the compound according to the first embodiment and second embodiment is represented by Formula II.

[0045] In a further alternative more preferred embodiment of the present invention, the compound according to the first embodiment and second embodiment is represented by Formula III.

[0046] In a most preferred embodiment of the present invention, the compound according to the first embodiment is selected from the group consisting of:

[0047] In an alternative most preferred embodiment of the present invention, the compound according to the first embodiment is selected from the group consisting of:

[0048] In a further alternative most preferred embodiment of the present invention, the compound according to the first embodiment is selected from the group consisting of:

[0049] In a most preferred embodiment of the present invention, the compound according tothe second embodiment is selected from the group consisting of:

[0050] In an alternative most preferred embodiment of the present invention, the compound according to the second embodiment is selected from the group consisting of:

[0051] In a further alternative most preferred embodiment of the present invention, the compound according to the second embodiment is selected from the group consisting of:

[0052] Various processes for synthesizing the compounds according to the present inventionas described in the above embodiments are herein provided below as third embodiment, fourth embodiment, fifth embodiment and sixth embodiment. The compounds obtained therefrom are ionic N-heterocyclic carbene (NHC)-transition metal compounds, which can be easily synthesized by the reaction of various NHC salts with transition metal sources in a broad range of solvents such as, for example, water, methanol, dichloromethane, etc. with high to excellent yields. The syntheses are typically completed within a short period of time, i.e. in about 1 h, at room temperature.

[0053] In the third embodiment, there is provided a process for synthesizing a compound according to the first embodiment or second embodiment, wherein the process comprises a step of reacting a N-heterocyclic carbene salt with a transition metal halide salt.

[0054] It is preferred in the third embodiment that the step of reacting a N-heterocyclic carbene salt with a transition metal halide salt is carried out in solution. Preferred N- heterocyclic carbene salts are N-heterocyclic carbene HX salts and N-heterocyclic carbene HBX4 salts, wherein X is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl. Preferred transition metal halide salts are IVbPdCU, M2PtX4, ZnX2and MAUX4, wherein M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na, and X is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl. More preferred transition metal halide salts are selected from Na2PdC14, K2PdC14, Na2PtC14, K2PtC14, ZnCl2, NaAuCL and KAuCL.

[0055] In the fourth embodiment of the present invention, there is provided a process for synthesizing a compound according to Formula I, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula A; and(ii) reacting said solution provided in step (i) with M2MxX4 to obtain a compound according to Formula I:Formula A Formula I wherein:= represents a single bond or a double bond;Z representswherein:R1is CFF-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M1is Pd; andX is a halogen atom, preferably F, C1, Br or I, more preferably C1 or Br, most preferably Cl.

[0056] In the fifth embodiment of the present invention, there is provided a process for synthesizing a compound according to Formula II, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula B; and(ii) reacting said solution provided in step (i) with M2M2X4 or M2X2 to obtain a compound according to Formula II:Formula B Formula II wherein:= represents a single bond or a double bond;Z representswherein:R1is CHa-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M2is Pt or Zn, preferably Pt; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0057] In the sixth embodiment of the present invention, there is provided a process for synthesizing a compound according to Formula III, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula C; and(ii) reacting said solution provided in step (i) with MM3X4 to obtain a compound according to Formula III:Formula C Formula III wherein:= represents a single bond or a double bond;Z representswherein:R1is CFF-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

[0058] It is preferred in the fourth embodiment, fifth embodiment and / or sixth embodiment that R1is CH3-yRy, wherein R is C1-C10 alkyl or C6-C10 aryl, and y is 1, 2 or 3, preferably 2; and R2is H, C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1. It is more preferred in the fourth embodiment, fifth embodiment and / or sixth embodiment that R1is CFF-yRy, wherein R is methyl, ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; and R2is H, methyl, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i-propoxy, phenyl, phenoxy or R1.

[0059] As an alternative, it is preferred in the fourth embodiment, fifth embodiment and / or sixth embodiment that R1is CFF-yRy, wherein R is C2-C10 alkyl or C6-C10 aryl, and y is 1, 2 or 3, preferably 2; and R2is H, C2-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1. As an alternative, it is more preferred in the fourth embodiment, fifth embodiment and / or sixth embodiment that R1is CFF-yRy, wherein R is ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; and R2is H, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i- propoxy, phenyl, phenoxy or R1.

[0060] Preferred, more preferred and most preferred embodiments for Z, R1, R2, M1, M2, M3and X in the fourth embodiment, fifth embodiment and / or sixth embodiment are the same as given above for the first embodiment and / or second embodiment of the present invention.

[0061] In the fourth embodiment, in step (ii), the solution comprising N-heterocyclic carbene cations according to Formula A provided in step (i) can be added to M2M1X4; or M2M1X4 can be added to the solution comprising N-heterocyclic carbene cations according to Formula A provided in step (i). M2MxX4 can be used as a solid or in the form of a solution. Preferred M2MXX4 is Na2PdCl4, and K2PdCl4.

[0062] In the fifth embodiment, in step (ii), the solution comprising N-heterocyclic carbene cations according to Formula B provided in step (i) can be added to M2M2X4 or M2X2; or M2M2X4 or M2X2can be added to the solution comprising N-heterocyclic carbene cations according to Formula B provided in step (i). M2M2X4 and M2X2 can be used as a solid or in the form of a solution. Preferred M2M2X4 is Na2PtC14 and K2PtC14. Preferred M2X2 is ZnCh.

[0063] In the sixth embodiment, in step (ii), the solution comprising N-heterocyclic carbene cations according to Formula C provided in step (i) can be added to MM3X4; or MM3X4 can be added to the solution comprising N-heterocyclic carbene cations according to Formula C provided in step (i). MM3X4 can be used as a solid or in the form of a solution. PreferredMM3X4is NaAuC14and KAuC14

[0064] Preferably, the solvent of the solution provided in step (i) of the fourth embodiment, fifth embodiment and / or sixth embodiment is selected from water, ketones, alcohols, or mixtures thereof. More preferably, the solvent of the solution provided in step (i) of the fourth embodiment, fifth embodiment and / or sixth embodiment is selected from water, acetone, methyl isopropyl ketone, ethyl isopropyl ketone, butanone, methyl isobutyl ketone, 2- pentanone, 3-pentanone, 3-methyl-2-pentanone, 2-hexanone, methanol, ethanol, glycol, 1- propanol, 2-propanol, 1,2-propanediol, 1,3 -propanediol, glycerin, 1-butanol, 2-methyl-l- propanol, 2-butanol, 2-methyl-2-propanol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3- butanediol, 1,2,3-butanetriol, 1,2,4-butanetriol, 2-methyl-l,2,3-propanetriol, or mixtures thereof. Most preferably, the solvent of the solution provided in step (i) of the fourth embodiment, fifth embodiment and / or sixth embodiment is a mixture of water and methanol.

[0065] Preferably, the reaction in step (ii) of the fourth embodiment, fifth embodiment and / or sixth embodiment of the present invention is carried out at a temperature in the range from about -10 °C to about 50 °C, preferably at a temperature in the range from about 0 °C to about 40 °C, more preferably at a temperature in the range from about 10 °C to about 30 °C, most preferably at a temperature in the range from about 20 °C to about 25 °C.

[0066] The ionic NHC-transition metal compounds according to the present show excellent catalytic activities in various transition metal-mediated organic reactions including, but not limited to, Suzuki-Miyaura cross -coupling reactions, Buchwald-Hartwig amination reactions, ester / amide trans-amidation reactions and other C-C or C-heteroatom coupling reactions. See Figure 2 for non-limiting examples of the reactions mentioned.

[0067] The reactions show similar or better yields in comparison to commercially available state-of-the-art NHC-transition metal compounds such as, for example, PEPPSI-IPr, NHC- Crotyl-Pd, etc.. Hence, there is further provided a method for performing transition metal- mediated organic reactions using the compound according to the present invention for catalysis.

[0068] Thus, in the seventh embodiment of the present invention, there is provided a method for performing a transition metal-catalyzed reaction between a first substrate and a second substrate, wherein the method comprises the following steps:(a) providing a compound according to the first embodiment or second embodiment ofthe present invention as a precatalyst in a reaction vessel;(b) adding a first substrate and a second substrate to the reaction vessel; and(c) reacting the first substrate and the second substrate at a temperature and a time sufficient to perform a transition metal-catalyzed reaction.

[0069] Preferably, in the seventh embodiment of the present invention, the compound provided in step (a) is represented by one of Formula I, Formula II or Formula III:wherein:M1is Pd;M2is Pt or Zn, preferably Pt;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl; and= and Z are defined as in the first embodiment or second embodiment.

[0070] More preferably, in the seventh embodiment of the present invention, the compound provided in step (a) is represented by Formula I:Formula I wherein:M1is Pd;X is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl; and= and Z are defined as in the first embodiment or second embodiment.

[0071] Preferred, more preferred and most preferred embodiments for Z, R1, R2, M1, M2, M3and X in the seventh embodiment are the same as given above for the first embodiment of the present invention.

[0072] Preferred, more preferred and most preferred embodiments for Z, R1, R2, M1, M2, M3and X in the seventh embodiment are the same as given above for the second embodiment of the present invention.

[0073] Hence, it is preferred in the seventh embodiment that Z represents a group selected fromwherein:R1is CH3-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and

[0074] Hence, as an alternative, it is preferred in the seventh embodiment that Z represents a group selected fromwherein:R1is CH3-yRy, wherein R is C2-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C2-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site.

[0075] Most preferably, in the seventh embodiment of the present invention, the compound provided in step (a) is selected from the group consisting of:

[0076] In a preferred embodiment of the seventh embodiment, the transition metal-catalyzed reaction is selected from a C(sp2)-C(sp2) coupling reaction, a C(sp2)-N coupling reaction, a C(sp2)-0 coupling reaction, a C(sp2)-S coupling reaction, a C(sp2)-P coupling reaction or an ester / amide trans-amidation reaction.

[0077] In a more preferred embodiment of the seventh embodiment, the transition metal-catalyzed reaction is selected from a Suzuki-Miyaura cross-coupling reaction, a Buchwald- Hartwig amination reaction or an ester / amide / / xz / z.s-amidation reaction.

[0078] Preferably, the temperature in step (c) of the method for performing a transition metal-catalyzed reaction according to the seventh embodiment is in the range from about 20 °C to about 130 °C, more preferably from about 30 °C to about 120 °C, and most preferably from about 40 °C to about 110 °C.

[0079] Preferably, when performing a Suzuki-Miyaura cross-coupling reaction or a Buchwald-Hartwig amination reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from an aromatic compound, which is substituted with a halogen atom, preferably Br or Cl, and optionally contains one or more substituents selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, halogen, hydroxy, nitro, and nitrile.

[0080] More preferably, when performing a Suzuki-Miyaura cross-coupling reaction or a Buchwald-Hartwig amination reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from a Ce-Cis aromatic compound, which is substituted with a halogen, preferably Br or Cl, and optionally contains one or more substituents selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, Ce- Cio aryloxy, C3-C9 heteroaryl, C3-C9 heteroaryloxy, F, Br, Cl, I, hydroxy, nitro, and nitrile.

[0081] Most preferably, when performing a Suzuki-Miyaura cross-coupling reaction or a Buchwald-Hartwig amination reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from a Ce aromatic compound, which is substituted with Br or Cl, and optionally contains one or more substituents selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, Ce aryl, Ce aryloxy, F, Br, Cl, I, hydroxy, nitro, and nitrile.

[0082] Preferably, when performing an ester / amide trans- amidation reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from an ester compound or an amide compound, preferably from R ’-CO-O-R1or R ’-CO-NR2- R1, wherein R1is an alkyl group or an aryl group, and R2is an alkyl group, an aryl group or an alkyloxycarbonyl group.

[0083] More preferably, when performing an ester / amide trans-amidation reaction, the firstsubstrate provided in step (b) of the method according to the seventh embodiment is R’-CO- O-R1or R^CO-NR^R1, wherein R1is a C1-C10 alkyl group or a C6-C10 aryl group, and R2is a C1-C10 alkyl group, a C6-C10 aryl group or an alkyloxycarbonyl group.

[0084] Most preferably, when performing an ester / amide trans-amidation reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is R’-CO- O-R1or R1-CO-NR2-R1, wherein R1is a C1-C5 alkyl group or a C<> aryl group, and R2is a Ci- C5 alkyl group, a C<> aryl group or a tert-butyloxycarbonyl group.

[0085] Preferably, when performing a Suzuki-Miyaura cross-coupling reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is an aromatic boronic acid compound, which optionally contains one or more substituents selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, halogen, hydroxy, nitro, and nitrile.

[0086] More preferably, when performing a Suzuki-Miyaura cross-coupling reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a Ce-Cis aromatic boronic acid compound, which optionally contains one or more substituents selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy, C3-C9 heteroaryl, C3-C9 heteroaryloxy, F, Br, Cl, I, hydroxy, nitro, and nitrile.

[0087] Most preferably, when performing a Suzuki-Miyaura cross -coupling reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a C<> aromatic boronic acid compound, which optionally contains one or more substituents selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C<> aryl, C<> aryloxy, F, Br, Cl, I, hydroxy, nitro, and nitrile.

[0088] Preferably, when performing a Buchwald-Hartwig amination reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is an amine compound, which contains one or two substituents selected from the group consisting of alkyl, cycloalkyl, and aryl.

[0089] More preferably, when performing a Buchwald-Hartwig amination reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is an amine compound, which contains one or two substituents selected from the group consisting of C1-C10 alkyl, C3-C10 cycloalkyl, and C6-C10 aryl.

[0090] Most preferably, when performing a Buchwald-Hartwig amination reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is an amine compound, which contains one or two substituents selected from the group consisting of C1-C5 alkyl, C3-C5 cycloalkyl, and Ce aryl.

[0091] Preferably, when performing an ester / amide trans-amidation reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is an aromatic amine compound, which optionally contains one or more substituents selected from the group consisting of alkyl, alkoxy, aryl, aryloxy, heteroaryl, heteroaryloxy, halogen, hydroxy, nitro, and nitrile.

[0092] More preferably, when performing an ester / amide trans-amidation reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a Ce-Cis aromatic amine compound, which optionally contains one or more substituents selected from the group consisting of C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy, C3-C9 heteroaryl, C3-C9 heteroaryloxy, F, Br, Cl, I, hydroxy, nitro, and nitrile.

[0093] Most preferably, when performing an ester / amide trans-amidation reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a C<> aromatic amine compound, which optionally contains one or more substituents selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, Ce aryl, Ce aryloxy, F, Br, Cl, I, hydroxy, nitro, and nitrile.

[0094] Preferably, step (c) of the method according to the seventh embodiment is carried out in the presence of a base. Preferred bases are selected from the group consisting of NaOH, KOH, NaOEt, KOEt, NaOtBu, KOtBu, Na2CO3and K2CO3.

[0095] It is to be understood that the skilled person can freely combine the above-mentioned preferred, more preferred and most preferred embodiment relating to one of the embodiments of the present invention in any desired way.Definitions

[0096] As used herein, the term “N-heterocyclic carbene” or “NHC”, as abbreviated, refers to a group of organic chemical compounds that are electron-rich, aromatic or unsaturated heterocyclic compounds capable of forming stable carbenes. The high stability of NHCscompared to other carbenes is mainly caused by the -I and +M effects of the neighboring heteroatoms, which increase the electron density of the empty p-orbital on the carbon atom. In addition to nitrogen, sulfur or oxygen can also stabilize the carbene. NHCs with imidazole as a backbone are additionally stabilized by their aromaticity. Free carbenes are usually obtained by deprotonation of imidazolium salts or the corresponding cationic precursor compounds. Typically, strong bases such as, for example, sodium hydride or alcoholates are used. NHCs play an important role as ligands for metal complexes. Due to their properties as strong sigma donors and their kinetic inertness, they represent a popular alternative to phosphines, especially for transition metal catalysis. Transition metal NHC complexes are often more temperature stable and less sensitive to oxidation than phosphine complexes.

[0097] As used herein, the term “room temperature” refers to an indoor ambient temperature, generally considered to be 20 °C.

[0098] As used herein, the term “about” or “approximately”, when used in connection with a measurable numerical variable, refers to the indicated value of the variable and to all values of the variable that tare within the experimental error of the indicated value (e.g., within 95% confidence limit for the mean) or within ± 10%, preferably ± 5%, of the indicated value, whichever is greater.

[0099] As used herein, the term “tBu” refers to a tert-butyl group, i.e. a branched alkyl group of formula (-C4H9), which may also be written as (-C(CH3)3).

[0100] As used herein, the term “iPr” refers to an Ao-propyl group, i.e. a branched alkyl group of formula (-C3H7), which may also be written as (-CH(CH3)2).

[0101] As used herein, the term “alkyl” refers to a saturated hydrocarbon chain, such as, but not limited to, methyl, ethyl, propyl and butyl. The alkyl group may be straight-chain or branched-chain. For example, as used herein, propyl encompasses both / -propyl and iso- propyl butyl encompasses n-butyl, sec -butyl, iso- butyl and tert-butyl, and so forth.

[0102] As used herein, the term “cycloalkyl” refers to a saturated hydrocarbon cyclic group, such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl (Cy). Also included are bridged saturated hydrocarbon (poly)cyclic groups such as, but not limited to, adamantyl.

[0103] As used herein, the term “aryl” refers to an aromatic hydrocarbon group. Aryl includes, e.g., phenyl, biphenyl, naphthyl, anthracenyl, and so forth, as well as the substituted forms of each.

[0104] As used herein, the term “heteroaryl” refers to an aromatic group containing one or more heteroatoms. Preferably, said heteroatoms are selected from O, N and / or S. Heteroaryl includes, e.g., furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-triazinyl, indolyl, benzofuranyl, benzoxazolyl, isoquinolyl, quinolyl, quinazolinyl, quinoxalinyl, benzoxazinyl, purinyl, pteridinyl and so forth, as well as the substituted forms of each.

[0105] “Substituted” as used herein means that one or more hydrogen atoms of the described compound or functional group is replaced with another functional group or substituent. For example, substituted phenyl may include one or more substituents in place of any hydrogen atom on the phenyl ring. In some embodiments, there may be one substituent at the ortho, meta or para position. In other embodiments, there may be substituents at both ortho positions or both meta positions. In still other embodiments, the optionally substituted phenyl may include substituents at, e.g., both the ortho and para positions, or both meta and para positions. In some embodiments with multiple substituents, the substituents are all the same, in other embodiments with multiple substituents, the substituents are different from each other. Typical substituents include, but are not limit to, C1-C4 alkyl, C1-C4 haloalkyl and C1-C4 alkoxy. When a compound or a functional group is described as “optionally substituted” that compound or functional group may have one or more substituents or no substituents.

[0106] The present invention is further illustrated by the examples following hereinafter which shall in no way be construed as limiting. The skilled person will acknowledge that various modifications, additions and alternations may be made to the invention without departing from the spirit and scope of the present invention.ExamplesSynthesis of ionic NHC-transition metal complexes

[0107] Example 1: Synthesis of ionic NHC-Pd complexes 3a-3gX = Cl or BF43a R = 2,6-diisopropylbenzene3b R = 2,6-dibenzhydryl-4-methyl-phenyl3c R = 2,6-dibenzhydryl-4-methoxy-phenyl3d R = 2,4,6-tribenzhydrylphenyl3e R = 2,6-diisopropylbenzene, saturated3f R = 2,6-di-3-pentylphenyl3g R = cyclohexyl

[0108] In a 20-mL vial charged with NHC-HX (X = C1 or BF4, 0.5 mmol, 1.0 equiv.) and a stirring bar was added MeOH (3 mL). In a separated 20-mL vial was added NaiPdCL (147 mg, 0.5 mmol, 1.0 equiv.) and H2O (3 ml) to prepare a palladium solution, which was added into the previous MeOH slurry in 5 minutes at room temperature. The resulting apricot color slurry was allowed to stir at the same temperature for another hour. At the conclusion of reaction, H2O (15 mL) was added into the reaction mixture and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 ml) and Et20 (25 ml), collected and dried to afford the desired apricot color complex 3a-3g.

[0109] Complex 3a:

[0110] Complex 3a ([IPr-H]2Pd2C16), following the general procedure with IPr-HC1 (1,3- bis(2,6-diisopropylphenyl)imidazolium chloride), 92% yield.

[0111] 1H NMR (500 MHz, CD2CI2) δ 8.87 (s, 1H), 8.05 (d, 2H), 7.70 (t, 2H), 7.46 (d, 4H),2.51 (hept, 4H), 1.36 (d, 12H), 1.29 (d, 12H).

[0112] Complex 3b :

[0113] Complex 3b ([IPr*-H]2Pd2C16), following the general procedure with IPr* HCl (N,N’-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazolium chloride), 88% yield.

[0114] 1H NMR (500 MHz, CD2CI2) δ 10.77 (t, J = 1.6 Hz, 1H), 7.38 - 7.32 (m, 8H), 7.27 - 7.21 (m, 12H), 7.21 - 7.11 (m, 12H), 6.88 (s, 4H), 6.78 (dd, 7 = 7.1, 1.9 Hz, 8H), 5.50 (d, J = 1.5 Hz, 2H), 5.20 (s, 4H), 2.27 (s, 6H).

[0115] Complex 3c :

[0116] Complex 3c ([IPr*OMe-H]2Pd2C16), following the general procedure withIPr*OMe-HBF4(N,N’-bis(2,6-bis(diphenylmethyl)-4-methoxyphenyl)imidazolium tetrafluoroborate), 80% yield.

[0117] 1H NMR (500 MHz, CD2CI2) δ 9.76 (t, J= 1.6 Hz, 1H), 7.34 - 7.17 (m, 24H), 7.12 - 7.01 (m, 8H), 6.89 - 6.78 (m, 8H), 6.54 (s, 4H), 5.67 (d, J= 1.5 Hz, 2H), 5.04 (s, 4H), 3.57 (s, 6H).

[0118] Complex 3d :

[0119] Complex 3d ([IPr#-H]2Pd2C16), following the general procedure with IPr# HC1 (1,3- bis(2,4,6-tribenzhydrylphenyl)-lH-imidazol-3-ium chloride), single crystals that are suitable for crystallographic analysis were obtained by pentane / acetone at room temperature, 92% yield.

[0120] 1H NMR (500 MHz, acetone-d6) δ 10.43 (t, J = 1.6 Hz, 1H), 7.28 - 7.14 (m, 36H), 7.01 (s, 2H), 6.96 (dd, 7 = 6.9, 1.9 Hz, 8H), 6.90 - 6.81 (m, 18H), 5.59 (s, 2H), 5.14 (s, 4H).

[0121] Complex 3e:

[0122] Complex 3e ([SIPr-HhPdjCle), following the general procedure with SIPr-HC1 (1,3- bis(2,6-diisopropylphenyl)imidazolinium chloride), single crystals that are suitable for crystallographic analysis were obtained by pentane / acetone at room temperature, 91% yield.

[0123] 1H NMR (500 MHz, CD2CI2) δ 7.68 (s, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.34 (d, J = 7.8 Hz, 4H), 4.88 (s, 4H), 3.07 (hept, J = 6.8 Hz, 4H), 1.47 (d, J = 6.7 Hz, 12H), 1.25 (d, J = 6.9 Hz, 12H).

[0124] Complex 3f:

[0125] Complex 3f ([IPent-H]2Pd2C16), following the general procedure with IPent-HCl (l,3-bis(2,6-di(3-pentyl)phenyl)imidazolium chloride), 93% yield.

[0126] 1H NMR (500 MHz, CD2CI2) δ 8.10 (t, J= 1.7 Hz, 1H), 8.02 (d, 7= 1.6 Hz, 2H), 7.68 (t, 7= 7.8 Hz, 2H), 7.35 (d, 7= 7.9 Hz, 4H), 1.93 (tt, 7= 8.3, 6.0 Hz, 5H), 1.84 - 1.72 (m, 9H), 1.72 - 1.59 (m, 7H), 0.91 (t, 7 = 7.4 Hz, 12H), 0.77 (t, 7 = 7.4 Hz, 12H).

[0127] Complex 3g:?eCK / Ck ^ClCy'fC^'Cy r Cil^Pd\ ^C| / Pd"c Cil2

[0128] Complex 3g ([ICy-HhPchCle), following the general procedure with ICy-HBF4 (1,3- dicyclohexylimidazolium tetrafluoroborate), single crystals that are suitable for crystallographic analysis were obtained by pentane / acetone at room temperature, 63% yield.

[0129] 1H NMR (500 MHz, CD2CI2) δ 9.35 (t, J= 1.7 Hz, 1H), 7.49 (d, J= 1.5 Hz, 2H), 4.71 (tt, J= 11.9, 3.9 Hz, 2H), 2.46 - 2.31 (m, 4H), 2.04 - 1.93 (m, 4H), 1.90 - 1.71 (m, 6H), 1.70 - 1.58 (m, 4H), 1.35 (qt, J = 13.0, 3.8 Hz, 2H).

[0130] Example 2: Synthesis of ionic NHC-Pt Complex 4b

[0131] In a 20-mL vial charged with la (IPr-HCl) (213 mg, 0.5 mmol, 2.0 equiv.) and a stirring bar was added MeOH (3 mL). In a separated 20-mL vial was added 4a (K^PtCLr) (104 mg, 0.25 mmol, 1.0 equiv.) and H2O (3 ml) to prepare a platinum solution, which was added into the previous MeOH solution in 5 minutes at room temperature. The resulting slurry was allowed to stir at the same temperature for another hour. At the conclusion of reaction, H2O (15 mL) was added into the reaction mixture and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 ml) and Et20 (25 ml), collected and dried to afford the desired Complex 4b ([IPr-HhPtCL).

[0132] 1H NMR (500 MHz, CD2CI2) δ 8.58 (t, J= 1.7 Hz, 1H), 8.44 (d, J= 1.7 Hz, 2H), 7.59 (t, J = 7.8 Hz, 2H), 7.37 (d, J = 7.9 Hz, 4H), 2.49 (hept, J = 6.8 Hz, 4H), 1.30 (d, J = 6.8 Hz, 12H), 1.19 (d, 7 = 6.9 Hz, 13H).

[0133] Example 3: Synthesis of ionic NHC-Zn Complex 5b

[0134] In a 20-mL vial charged with le (SIPr-HCl) (214 mg, 0.5 mmol, 2.0 equiv.) and a stirring bar was added MeOH (3 mL). In a separated 20-mL vial was added 5a (ZnCh) (34 mg, 0.25 mmol, 1.0 equiv.) and H2O (3 ml) to prepare an zinc solution, which was added into the previous MeOH solution in 5 minutes at room temperature. The resulting slurry was allowed to stir at the same temperature for another hour. At the conclusion of reaction, H2O (15 mL) was added into the reaction mixture and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 ml) and Et20 (25 ml), collected and dried to afford the desired Complex 5b (|SIPr-H hZnCL).

[0135] 1H NMR (500 MHz, CDC13) δ 7.43 (t, J= 7.8 Hz, 2H), 7.35 (d, J= 1.5 Hz, 1H), 7.24 (dd, J= 7.8, 1.0 Hz, 4H), 5.04 (d, J= 1.7 Hz, 4H), 3.13 (heptd, J= 6.9, 1.6 Hz, 4H), 1.39 (dd, 7 = 6.8, 2.0 Hz, 12H), 1.17 (d, 7= 6.8 Hz, 12H).

[0136] Example 4: Synthesis of ionic NHC-Au Complex 6b

[0137] In a 20-mL vial charged with le (SIPr-HCl) (214 mg, 0.5 mmol, 1.0 equiv.) and a stirring bar was added MeOH (3 mL). In a separated 20-mL vial was added 6a (KAuCL) (189 mg, 0.5 mmol, 1.0 equiv.) and H2O (3 ml) to prepare a gold solution, which was added into the previous MeOH solution in 5 minutes at room temperature. The resulting slurry was allowed to stir at the same temperature for another hour. At the conclusion of reaction, H2O (15 mL) was added into the reaction mixture and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 ml) and Et20 (25 ml), collected and dried to afford the desired Complex 6b ([SIPr-H]AuC14).

[0138] 1H NMR (500 MHz, CD2CI2) δ 7.97 (s, 1H), 7.56 (t, 7 = 7.8 Hz, 2H), 7.36 (d, 7 = 7.8Hz, 4H), 4.61 (d, J= 0.6 Hz, 4H), 2.97 (hept, J = 6.9 Hz, 4H), 1.43 (d, J= 6.9 Hz, 12H), 1.28 (d, 7= 6.9 Hz, 12H).Application of ionic NHC-transition metal complexes in transition metal-mediated organic reactions

[0139] Example 5: Suzuki-Miyaura cross coupling reaction

[0140] In a 4-mL vial charged with various precatalysts (1.0 mol%), KOH (56 mg, 1.0 mmol, 2.0 equiv.) and a stirring bar was added 2-MeTHF (1 mL), 2-chlorotoluene (0.5 mmol, 1.0 equiv.) and 2,6-dimethyl-phenylboronic acid (0.75 mmol, 1.5 equiv.). The resulting mixture was allowed to stir at 40 °C for 90 min. The reaction yields were determined by GC and are shown in Table 1 below.

[0141] Table 1: Reactions of Example 5

[0142] Structures of the known complexes (IPr)Pd(cin)C1

[0013] , PEPPSI-IPr (CAS: 905459- 27-0) and (IPr)Pd(ind)C1 [2b],

[0013] used in Example 5:

[0143] Example 6: Suzuki-Miyaura cross coupling reaction

[0144] In a 4-mL vial charged with various precatalysts (2.0 mol%), KOH (56 mg, 1.0 mmol, 2.0 equiv.) and a stirring bar was added 2-MeTHF (3 mF), 2-chloro-m-xylene (0.5 mmol, 1.0 equiv.) and 2,4,6-trimethyl-phenylboronic acid (0.75 mmol, 1.5 equiv.). The resulting mixture was allowed to stir at 60 °C for 24 h. The conversions were determined by GC and are shown in Table 2 below.

[0145] Table 2: Reactions of Example 6

[0146] Example 7: Suzuki-Miyaura cross coupling reaction

[0147] In a 4-mL vial charged with Complex 3a ([IPr-HhPdiCle) (3.2 mg, 1.0 mol%), KOH (56 mg, 1.0 mmol, 2.0 equiv.) and a stirring bar was added 2-MeTHF (1 mL), Ar / Het-C1 (0.5 mmol, 1.0 equiv.) and R1-B(pin) (0.75 mmol, 1.5 equiv.). The resulting mixture was allowed to stir at 55 °C for 5 hours. At the conclusion of reaction, all volatiles were removed under vacuo and the residue was further purified via silica gel column to obtain the desired product as shown in the following.

[0148] Product 7.1

[0149] 2, 2’ ,6-Trimethyl-l,l’ -biphenyl: 81% yield. (15 H00 N MMHRz, CDC13) δ 7.36 - 7.14 (m, 6H), 7.07 (dt, J = 7.2, 2.1 Hz, 1H), 2.02 (d, J = 1.9 Hz, 3H), 2.00 (d, J = 2.0 Hz, 6H).

[0150] Product 7.2

[0151] 2-(2,6-Dimethylphenyl)-3-methylpyridine: 91% yield.1H NMR (500 MHz, CDC13) δ 8.55 (dd, J= 4.9, 1.7 Hz, 1H), 7.59 (ddd, J = 7.7, 1.7, 0.8 Hz, 1H), 7.18 (ddd, J = 8.2, 5.9, 4.0 Hz, 2H), 7.10 (d, J= 7.3 Hz, 2H), 2.02 (s, 3H), 1.95 (s, 6H).

[0152] Product 7.3

[0153] 2,2’,6,6’-Tetramethyl-l,r-biphenyl: 84% yield with Complex 3b ([IPr*-H]2Pd2C16, 1.0 mol%) as the catalyst.1H NMR (500 MHz, CDC13) δ 7.17 (dd, J= 8.7, 6.1 Hz, 2H), 7.14 - 7.10 (m, 4H), 1.90 (d, J = 0.8 Hz, 11H).

[0154] Example 8: Buchwald-Hartwig amination reactionH 0.5 mol% 3b, NaOtBu R2

[0155] In a 4-mL vial charged with Complex 3b ([IPr*-H]2Pd2C16) (5.6 mg, 0.5 mol%),NaOtBu (144 mg, 1.5 mmol, 1.5 equiv.) and a stirring bar was added 2-MeTHF (1 mL), Ar-Cl (1.0 mmol, 1.0 equiv.) and a primary or secondary amine (1.5 mmol, 1.5 equiv.). The resulting mixture was allowed to stir at 55 °C for 5 hours. At the conclusion of reaction, all volatiles were removed under vacuo and the residue was further purified via silica gel column to obtain the desired product as shown in the following.

[0156] Product 8.1

[0157] N-(2,6-Dimethylphenyl)-2,6-dimethylbenzenamine: 97% yield.1H NMR (500 MHz, CDC13) δ 6.98 (d, 7= 7.4 Hz, 4H), 6.84 (t, 7 = 7.4 Hz, 2H), 4.80 (s, 1H), 2.01 (s, 12H).

[0158] Product 8.2

[0159] N-Cyclobutyl-4-quinolinamine: 90% yield.1H NMR (500 MHz, CDCI3) δ 9.46 (d, 7 = 5.3 Hz, 1H), 8.91 (dd, 7= 8.5, 1.3 Hz, 1H), 8.69 (dd, 7= 8.4, 1.3 Hz, 1H), 8.54 (ddd, 7= 8.3, 6.8, 1.4 Hz, 1H), 8.34 (ddd, 7= 8.3, 6.8, 1.3 Hz, 1H), 7.25 (d, 7 = 5.3 Hz, 1H), 6.20 (d, 7 = 5.1 Hz, 1H), 5.11 - 4.95 (m, 1H), 3.54 - 3.39 (m, 2H), 3.01 - 2.72 (m, 4H).

[0160] Product 8.3

[0161] N,3-Dimethyl-N-phenyl-2-pyridinamine: 87% yield.1H NMR (500 MHz, CDC13) δ 8.32 (dd, J= 4.9, 1.9 Hz, 1H), 7.43 (ddd, J= 7.3, 1.9, 0.9 Hz, 1H), 7.25 - 7.19 (m, 2H), 6.97 (dd, 7= 7.4, 4.8 Hz, 1H), 6.90 (tt, 7 = 7.3, 1.1 Hz, 1H), 6.79 - 6.74 (m, 2H), 3.42 (s, 3H), 1.93 (s, 3H).

[0162] Product 8.4

[0163] N-Butyl-3-methyl-2-pyridinamine: 93% yield.1H NMR (500 MHz, CDC13) δ 8.02 (dt, J = 5.2, 1.2 Hz, 1H), 7.19 (ddq, 7 = 7.1, 1.8, 0.9 Hz, 1H), 6.49 (dd, J = 7.1, 5.1 Hz, 1H), 4.05 (s, 1H), 3.46 (td, J= 7.2, 5.3 Hz, 2H), 2.07 (s, 3H), 1.69 - 1.56 (m, 2H), 1.51 - 1.38 (m, 2H), 0.96 (t, 7 = 7.3 Hz, 3H).

[0164] Product 8.5

[0165] N,N-Dibutyl-3-methyl-2-pyridinamine: 91% yield.1H NMR (500 MHz, CDC13) δ 8.14 (ddd, 7 = 4.9, 1.9, 0.7 Hz, 1H), 7.36 (ddt, 7 = 7.4, 1.6, 0.8 Hz, 1H), 6.78 (dd, 7 = 7.3, 4.8 Hz, 1H), 3.19 - 3.10 (m, 4H), 2.24 (s, 3H), 1.51 - 1.41 (m, 4H), 1.27 (dq, 7 = 14.7, 7.4 Hz, 4H), 0.87 (t, 7 = 7.4 Hz, 6H).

[0166] Product 8.6

[0167] N-(l,l-Dimethylethyl)-3-methyl-2-pyridinamine: 94% yield (isolated as HC1 salt). 1 H NMR (500 MHz, CDC13) δ 14.07 (d, 7 = 27.5 Hz, 1H), 8.46 (t, 7 = 7.1 Hz, 1H), 7.61 (d, 7 = 7.1 Hz, 1H), 6.77 (qd, 7 = 6.8, 5.5, 2.1 Hz, 1H), 5.29 (d, 7 = 24.1 Hz, 1H), 2.26 (d, 7 = 2.6 Hz, 3H), 1.75 - 1.68 (m, 9H).

[0168] Example 9: Ester trans- amidation reaction

[0169] In a 4-mL vial charged with Complex 3b ([IPr*-H]2Pd2C16) (8.4 mg, 3 mol%), K2CO3 (104 mg, 0.75 mmol, 1.5 equiv.), p-anisidine (62 mg, 0.5 mmol, 2.0 equiv.), phenyl benzoate (0.25 mmol, 1.0 equiv.) and a stirring bar was added DME (1 mL). The resulting mixture was allowed to stir at 100 °C for 15 hours. At the conclusion of reaction, all volatiles were removed under vacuo and the residue was further purified via silica gel column to obtain the desired product.

[0170] 4’ -Methoxybenzanilide: 84% yield.1H NMR (500 MHz, CDC13) δ 7.86 (dt, 7 = 7.1, 1.4 Hz, 2H), 7.75 (s, 1H), 7.59 - 7.51 (m, 3H), 7.51 - 7.44 (m, 2H), 6.94 - 6.86 (m, 2H), 3.82 (s, 3H).

[0171] Example 10: Amide trans-amidation reactions

[0172] In a 4-mL vial charged with Complex 3b ([IPr*-H]2Pd2C16) (8.4 mg, 3 mol%), K2CO3 (104 mg, 0.75 mmol, 1.5 equiv.), p-anisidine (62 mg, 0.5 mmol, 2.0 equiv.), tertiary amide (0.25 mmol, 1.0 equiv.) and a stirring bar was added DME (1 mL). The resulting mixture was allowed to stir at 100 °C for 15 hours. At the conclusion of reaction, all volatiles were removed under vacuo and the residue was further purified via silica gel column to obtain the desired product.

[0173] 4’ -Methoxybenzanilide: 84% yield.1H NMR (500 MHz, CDC13) δ 7.86 (dt, 7 = 7.1, 1.4 Hz, 2H), 7.75 (s, 1H), 7.59 - 7.51 (m, 3H), 7.51 - 7.44 (m, 2H), 6.94 - 6.86 (m, 2H), 3.82 (s, 3H).

[0174] The examples provided herein are by no way intended to limit the scope of the invention as set forth in the claims.References

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Claims

We claim:

1. A compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, wherein the N-heterocyclic carbene cation is:wherein:= represents a single bond or a double bond;Z represents a group selected fromwherein:R1is CH3-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andwherein the transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms; with the proviso that the following compounds are excluded:

2. The compound according to claim 1, whereinR1is Cth-yRy, wherein R is C1-C10 alkyl or C6-C10 aryl, and y is 1, 2 or 3, preferably 2; andR2is H, C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1.

3. The compound according to claim 1 or 2, whereinR1is CHa-yRy, wherein R is methyl, ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; andR2is H, methyl, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i-propoxy, phenyl, phenyloxy or R1.

4. A compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, wherein the N-heterocyclic carbene cation is:wherein:= represents a single bond or a double bond;Z represents a group selected fromwherein:R1is Cth-yRy, wherein R is C2-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C2-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; and represents a binding site; and wherein the transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms.

5. The compound according to claim 4, whereinR1is CH3-yRy, wherein R is C2-C10 alkyl or C6-C10 aryl, and y is 1, 2 or 3, preferably 2; andR2is H, C2-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1.

6. The compound according to claim 4 or 5, whereinR1is CH3-yRy, wherein R is ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; andR2is H, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i-propoxy, phenyl, phenyloxy or R1.

7. The compound according to any one of claims 1 to 6, wherein the transition metal atom is selected from groups 10, 11 and 12 of the periodic table, preferably from the group consisting of Ni, Pd, Pt, Cu, Ag, Au, Zn, Cd and Hg, more preferably from the group consisting of Pd, Pt, Au and Zn.

8. The compound according to any one of claims 1 to 7, wherein the halogen atom is selected from the group consisting of F, Cl, Br and I, more preferably from the group consisting of C1 and Br, most preferably the halogen atom is Cl.

9. The compound according to any one of claims 1 to 8, wherein the transition metal halide anion is selected from the group consisting of:wherein:M1is Pd;M2is Pt or Zn, preferably Pt;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

10. The compound according to any one of claims 1 to 9, wherein the compound is represented by one of Formula I, Formula II or Formula III:Formula Ia IIFormula III wherein:M1is Pd;M2is Pt or Zn, preferably Pt;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl; and= and Z are defined as in claim 1 or 4.

11. A process for synthesizing a compound according to claim 1 or 4, wherein the process comprises a step of reacting a N-heterocyclic carbene salt with a transition metal halide salt.

12. The process according to claim 11, wherein the step of reacting a N-heterocyclic carbene salt with a transition metal halide salt is carried out in solution.

13. A process for synthesizing a compound according to Formula I, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula A; and(ii) reacting said solution provided in step (i) with M2M1X4 to obtain a compound according to Formula I:wherein:= represents a single bond or a double bond;Z representswherein:R1is CH3-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andrepresents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M1is Pd; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

14. A process for synthesizing a compound according to Formula II, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula B; and(ii) reacting said solution provided in step (i) with M2M2X4 or M2X2 to obtain a compound according to Formula II:Formula B Formula IIFormula B Formula II wherein:= represents a single bond or a double bond;Z representswherein:R1is CH3-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andrepresents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M2is Pt or Zn, preferably Pt; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

15. A process for synthesizing a compound according to Formula III, wherein the process comprises the following steps:(i) providing a solution comprising N-heterocyclic carbene cations according to Formula C; and(ii) reacting said solution provided in step (i) with MM3X4 to obtain a compound according to Formula III:Formula C Formula III wherein:= represents a single bond or a double bond;Z representswherein:R1is CFF-yRy, wherein R is C1-C20 alkyl or C6-C14 aryl, and y is 1, 2 or 3, preferably 2;R2is H, C1-C20 alkyl, C1-C20 alkoxy, C6-C14 aryl, C6-C14 aryloxy or R1; andrepresents a binding site;M is an alkali metal atom, preferably selected from Li, Na, K, Rb and Cs, more preferably selected from Li, Na and K, most preferably Na;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl.

16. The process according to any one of claims 13 to 15, wherein:R1is CH3-yRy, wherein R is C1-C10 alkyl or C6-C10 aryl, and y is 1, 2 or 3, preferably 2; andR2is H, C1-C10 alkyl, C1-C10 alkoxy, C6-C10 aryl, C6-C10 aryloxy or R1.

17. The process according to claim 16, whereinR1is CH3-yRy, wherein R is methyl, ethyl, n-propyl, i-propyl or phenyl, and y is 1, 2 or 3, preferably 2; andR2is H, methyl, ethyl, n-propyl, i-propyl, methoxy, ethoxy, n-propoxy, i-propoxy, phenyl, phenoxy or R1.

18. A method for performing a transition metal-catalyzed reaction between a first substrate and a second substrate, wherein the method comprises the following steps:(a) providing a compound according to one or more of claims 1 to 10 as a precatalyst in a reaction vessel;(b) adding a first substrate and a second substrate to the reaction vessel; and(c) reacting the first substrate and the second substrate at a temperature and a time sufficient to perform a transition metal-catalyzed reaction.

19. The method according to claim 18, wherein the compound provided in step (a) is represented by one of Formula I, Formula II or Formula III:Formula III wherein:M1is Pd;M2is Pt or Zn, preferably Pt;M3is Au; andX is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl; and= and Z are defined as in claim 1 or 4.

20. The method according to claim 18, wherein the compound provided in step (a) is represented by Formula I:Formula I wherein:M1is Pd;X is a halogen atom, preferably F, Cl, Br or I, more preferably C1 or Br, most preferably Cl; and= and Z are defined as in claim 1 or 4.

21. The method according to any one of claims 18 to 20, wherein the transition metal- catalyzed reaction is selected from a C(sp2)-C(sp2) coupling reaction, a C(sp2)-N coupling reaction, a C(sp2)-0 coupling reaction, a C(sp2)-S coupling reaction, a C(sp2)-P coupling reaction or an ester / amide trans-amidation reaction.

22. The method according to claim 21, wherein the transition metal-catalyzed reaction is selected from a Suzuki-Miyaura cross-coupling reaction, a Buchwald-Hartwig amination reaction or an ester / amide trans-amidation reaction.