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

Abstract

A new class of ionic N-heterocyclic carbene (NHC) transition metal compounds is provided, which can be prepared in excellent yield and purity by a synthesis route that is easily scalable. The ionic NHC-transition metal compounds show high catalytic activity and high reaction efficiency in various transition metal catalyzed reactions. Further provided are simple and scalable methods for synthesizing the ionic NHC-transition metal compounds, and methods for performing transition metal catalyzed reactions using the ionic NHC-transition metal compounds as precatalysts.

Description

Technical Field

[0001] A novel class of ionic N-heterocyclic carbene (NHC) transition metal compounds is presented, which can be used as pre-catalysts for transition metal-mediated organic reactions. Various NHC motifs can be incorporated into these novel ionic compounds via a readily scalable and simplified synthetic route starting from readily available substrates, carried out in a wide range of solvents, with simple post-processing, and excellent yields and purities. These ionic NHC transition metal compounds are inexpensive and free of organic auxiliary groups. All obtained ionic NHC transition metal compounds were thoroughly characterized using modern analytical methods such as NMR, elemental analysis, and single-crystal X-ray diffraction.

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

[0003] For example, ionic NHC-Pd complexes can be used as pre-catalysts in the following reactions: i) C(sp 2 )-C(sp 2 ii) Cross-coupling reactions (e.g., the Suzuki-Miyaura reaction), C(sp 2 )-N coupling reactions (e.g., Buchwald-Hartwig amination), iii) C(sp 2 )-O coupling reaction, iv) C(sp 2 )-S coupling reaction, v) C(sp 2 )-P coupling reaction, and vi) ester / amide to amide reaction (see Figure 1 It has similar or better yields compared to state-of-the-art commercially available NHC-Pd precatalysts such as PEPPSI-IPr.

[0004] The NHC-Pd precatalyst according to the present invention prevents the loss of precious metals during catalyst formation and is therefore more sustainable than conventional prior art precatalysts as mentioned above.

[0005] Furthermore, a simple and scalable method is provided for synthesizing the novel ionic NHC-transition metal compounds, which starts from readily available substrates, is carried out in a wide range of solvents, has simple post-processing, and offers excellent yields and purity.

[0006] Finally, a method is provided for carrying out a transition metal catalytic reaction between a first substrate and a second substrate using the aforementioned ionic NHC-transition metal compound as a precatalyst, wherein the transition metal catalytic reaction is preferably selected from C(sp... 2)-C(sp 2 Coupling reaction, C(sp) 2 )-N coupling reaction, C(sp 2 )-O coupling reaction, C(sp 2 )-S coupling reaction, C(sp 2 )-P coupling reaction or ester / amide to amide reaction (see Figure 1 More preferably, it is selected from the Suzuki-Miyaura cross-coupling reaction, the Buchwald-Hartwig amination reaction, or the ester / amide to amide reaction (see Suzuki-Miyaura cross-coupling reaction, Buchwald-Hartwig amination reaction, or ester / amide to amide reaction). Figure 2 ). Background Technology

[0007] Ligand-promoted palladium-catalyzed cross-coupling reactions are among the most important reaction classes in modern chemistry [1], in which L1Pd(0) is generally considered to be an active catalyst class in the cycle [2]. However, due to the instability of these catalytically active L1Pd(0) classes, they are usually preferred to be generated in situ.

[0008] In the early stages, the formation of catalytically active L1Pd(0) compounds is achieved by replacing the target ligand with stable Pd(0) precursors such as Pd2(dba)3 and Pd(PPh3)4, or by in-situ reduction of Pd(II) complexes with a reducing agent such as phosphine. While direct, the former releases free dba or PPh3 into the reaction system, which may act as a non-inert bystander class, while the latter consumes the valuable phosphine ligand. Furthermore, the formation of undefined coordination Pd(0) compounds can even complicate further mechanistic studies. To mitigate this, air-stable and well-defined Pd(II) precatalysts have been developed. Catalytically active L1Pd(0) compounds are generated upon activation, providing high catalytic efficiency in a wide range of cross-coupling reactions.

[0009] N-heterocyclic carbene (NHC) exhibits uniqueness in cross-coupling reactions catalyzed by different types of Pd or Ni[3]. Specifically, for air-stable and well-defined NHC-Pd(II) precatalysts, current development can be divided into two categories based on the auxiliary group. The first category includes N-heterocyclic carbene (NHC) ... 3 -Allyl groups, as auxiliary components, readily undergo reductive elimination reactions in the presence of bases or nucleophiles to generate Pd(0) complexes. However, disproportionation side reactions have been observed, especially for sterically less sterically hindered η groups. 3 -Allyl groups will significantly reduce the actual catalyst concentration overall[4].

[0010] To solve this problem, η, a spatial steric hindrance mechanism, was developed. 3 -Allyl as n 3-tBu-indenyl groups have shown high efficiency in challenging cross-coupling reactions [5]. The latest report in this field comes from Gooßen, where a methylnaphthalene-anchored NHC-palladium system outperforms all previous catalysts [6]. The second class is PEPPSI-IPr precatalysts, which contain nitrogen-based L-ligands such as pyridine or aniline to stabilize the complex [7]. Activation of such precatalysts typically follows L-ligand dissociation and reductive elimination steps to generate an active catalyst. While both of these precatalyst classes show high reaction efficiency, they suffer from high costs of scale-up synthesis and contamination of auxiliary groups during the reaction.

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

[0012] Strassner et al. reported asymmetrically substituted NHC palladium as tunable arylalkyl ionic liquids

[10] .

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

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

[12] .

[0014] Here we introduce another well-defined class of ionic NHC-transition metal compounds that are low in cost, free of organic auxiliary groups, and can be obtained in excellent yields and purities from readily available substrates in a wide range of solvents via easily scalable and simple synthetic routes.

[0015] Ionic NHC-transition metal compounds can be used as precatalysts in a variety of transition metal-mediated organic reactions, exhibiting high catalytic activity and high reaction efficiency, and preventing the loss of precious metals during catalyst formation, making them more sustainable than conventional existing precatalysts. Summary of the Invention

[0016] Novel ionic N-heterocyclic carbene (NHC) transition metal compounds are provided, comprising one or more NHC cations and one or more transition metal halide anions. Further, a simple and scalable method for synthesizing the ionic NHC-transition metal compound is provided, along with a method for using the ionic NHC-transition metal compound as a precatalyst to carry out a transition metal-catalyzed reaction between a first substrate and a second substrate.

[0017] Therefore, in a first embodiment of the present invention, a compound is provided comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions. The N-heterocyclic carbene cation is: in: Indicates a single bond or a double bond; Z indicates that it is selected from group, in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site; and The transition metal halide anion contains one or more transition metal atoms and one or more halogen atoms; The condition is that the following compounds are not included: .

[0018] In a second embodiment of the invention, a compound is provided comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions. The N-heterocyclic carbene cation is: in: Indicates a single bond or a double bond; Z indicates that it is selected from group, in: R 1 For CH 3-y R y Where R is C2-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C2-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site; and The transition metal halide anion contains one or more transition metal atoms and one or more halogen atoms.

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

[0020] In a fourth embodiment of the present invention, a method for synthesizing a compound according to Formula I is provided, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula A; and (ii) Mix the solution provided in step (i) with M2M 1 The X4 reaction yields the compound according to formula I: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 1 For Pd; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0021] In a fifth embodiment of the invention, a method for synthesizing a compound according to formula II is provided, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula B; and (ii) Mix the solution provided in step (i) with M2M 2 X4 or M 2 The X2 reaction yields the compound according to formula II: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 2 It can be Pt or Zn, with Pt preferred; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0022] In a sixth embodiment of the invention, a method for synthesizing a compound according to Formula III is provided, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula C; and (ii) Mix the solution provided in step (i) with MM 3 The X4 reaction yields the compound according to formula III: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0023] In a seventh embodiment of the present invention, a method for carrying out a transition metal catalytic reaction between a first substrate and a second substrate is provided, wherein the method includes the following steps: (a) Providing a compound according to the first or second embodiment of the invention as a pre-catalyst in a reaction vessel; (b) Add the first and second substrates to the reaction vessel; and (c) React the first and second substrates at a temperature and time sufficient for transition metal catalysis. Attached Figure Description

[0024] Figure 1 The following non-limiting examples of reactions are shown: i) C(sp 2 )-C(sp 2 ii) Cross-coupling reactions (e.g., the Suzuki-Miyaura reaction), C(sp 2 )-N coupling reactions (e.g., Buchwald-Hartwig amination), iii) C(sp 2 )-O coupling reaction, iv) C(sp 2 )-S coupling reaction, v) C(sp2 )-P coupling reaction, and vi) ester / amide to amide reaction.

[0025] Figure 2 Non-limiting examples of transition metal-catalyzed reactions are shown below: a) Suzuki-Miyaura cross-coupling reaction, b) Buchwald-Hartwig amination reaction, and c) ester / amide to amide reaction. Detailed Implementation

[0026] The compounds, methods for synthesizing the compounds, and methods for carrying out transition metal catalytic reactions according to the invention address known problems in catalysis and provide a powerful new platform to improve the yields of previously challenging cross-coupling reactions while reducing the loss of precious metals during catalyst formation, thereby contributing to improved sustainability.

[0027] The compounds according to the invention are readily synthesized and scaled up, inexpensive, and do not contain any organic auxiliary groups. They provide high reaction efficiency in transition metal-catalyzed reactions, including but not limited to the Suzuki-Miyaura cross-coupling reaction, the Buchwald-Hartwig amination reaction, and the ester / amide to amide conversion reaction. See also Figure 2 Non-limiting examples of the reactions described herein.

[0028] In a first embodiment of the invention, a compound is provided comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions. The N-heterocyclic carbene cation is: in: Indicates a single bond or a double bond; Z indicates that it is selected from group, in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site; and The transition metal halide anion contains one or more transition metal atoms and one or more halogen atoms; The condition is that the following compounds are not included: .

[0029] In the first embodiment, R is preferred. 1 For CH 3-y R y Where R is C1-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C1-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 In the first embodiment, R is more preferred. 1 For CH 3-y R y Wherein R is methyl, ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 H, methyl, Or R 1 .

[0030] In the first embodiment, the transition metal atoms are preferably 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, and more preferably from the group consisting of Pd, Pt, Au and Zn.

[0031] In the first embodiment, the halogen atom is preferably selected from the group consisting of F, Cl, Br and I, more preferably from the group consisting of Cl and B, and 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 consisting of 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 Cl 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 a second embodiment of the invention, a compound is provided comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions. The N-heterocyclic carbene cation is: in: Indicates a single bond or a double bond; Z indicates that it is selected from group, in: R 1 For CH 3-y R y Where R is C2-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C2-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site; and The transition metal halide anion contains one or more transition metal atoms and one or more halogen atoms.

[0034] In the second embodiment, R is preferred. 1 For CH 3-y R y Where R is C2-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C2-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 In the second embodiment, R is more preferred. 1 For CH 3-y R y Wherein R is ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 It can be H, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, phenyl, phenoxy, or R. 1 .

[0035] In the second embodiment, the transition metal atoms are preferably 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, and more preferably from the group consisting of Pd, Pt, Au and Zn.

[0036] In the second embodiment, the halogen atom is preferably selected from the group consisting of F, Cl, Br and I, more preferably from the group consisting of Cl and B, and 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 Cl 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] In the first and second embodiments, the transition metal halide anions are preferably selected from the group consisting of: in: M 1 For Pd; M 2 The material can be Pt or Zn, with Pt being preferred; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0039] More preferably in the first and second embodiments, the transition metal halide anion is... in: M 1 For Pd; and X is a halogen, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0040] As an alternative, a more preferred embodiment in the first and second embodiments is that the transition metal halide anion is... in: M 2 It can be Pt or Zn, with Pt preferred; and X is a halogen, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0041] As an alternative, in the first and second embodiments, it is more preferable that the transition metal halide anion is... in: M 3 For Au; and X is a halogen, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0042] In a preferred embodiment of the invention, the compound according to the first embodiment and the second embodiment is represented by one of formula I, formula II or formula III: in: M 1 For Pd; M 2 The material can be Pt or Zn, with Pt being preferred; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl; and And Z as defined in the first or second implementation scheme.

[0043] In a more preferred embodiment of the invention, the compounds according to the first and second embodiments are represented by Formula I.

[0044] In an alternative, more preferred embodiment of the invention, the compounds according to the first and second embodiments are represented by Formula II.

[0045] In another alternative, more preferred embodiment of the invention, the compounds according to the first and second embodiments are represented by Formula III.

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

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

[0048] In another alternative preferred embodiment of the invention, the compound according to the first embodiment is selected from the group consisting of: .

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

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

[0051] In another alternative preferred embodiment of the invention, the compound according to the second embodiment is selected from the group consisting of: .

[0052] Various methods for synthesizing compounds according to the invention as described in the above embodiments are provided below as third, fourth, fifth, and sixth embodiments. The resulting compounds are ionic N-heterocyclic carbene (NHC)-transition metal compounds, which can be readily synthesized by reacting various NHC salts with transition metal sources in a wide range of solvents such as, for example, water, methanol, dichloromethane, etc., with high to excellent yields. The synthesis is typically completed within a short time period, approximately one hour, at room temperature.

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

[0054] In the third embodiment, it is preferred that the step of reacting the N-heterocyclic carbene salt with the transition metal halide salt is carried out in solution. Preferred N-heterocyclic carbene salts are N-heterocyclic carbene HX salt and N-heterocyclic carbene HBF4 salt, wherein X is a halogen atom, preferably F, Cl, Br, or I, more preferably Cl or Br, and most preferably Cl. Preferred transition metal halide salts are M2PdCl4, M2PtX4, ZnX2, and 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, and most preferably Na, and X is a halogen atom, preferably F, Cl, Br, or I, more preferably Cl or Br, and most preferably Cl. More preferred transition metal halide salts are selected from Na2PdCl4, K2PdCl4, Na2PtCl4, K2PtCl4, ZnCl2, NaAuCl4, and KAuCl4.

[0055] In a fourth embodiment of the present invention, a method for synthesizing a compound according to Formula I is provided, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula A; and (ii) Mix the solution provided in step (i) with M2M 1 The X4 reaction yields the compound according to formula I: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 1 For Pd; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0056] In a fifth embodiment of the invention, a method for synthesizing a compound according to formula II is provided, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula B; and (ii) Mix the solution provided in step (i) with M2M 2 X4 or M 2 The X2 reaction yields the compound according to formula II: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 2 It can be Pt or Zn, with Pt preferred; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0057] In a sixth embodiment of the invention, a method for synthesizing a compound according to Formula III is provided, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula C; and (ii) Mix the solution provided in step (i) with MM 3 The X4 reaction yields the compound according to formula III: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

[0058] In the fourth, fifth, and / or sixth implementation schemes, R is preferred. 1 For CH 3-y R y Where R is C1-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C1-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 In the fourth, fifth, and / or sixth embodiments, R is more preferred. 1 For CH 3-y R y Wherein R is methyl, ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 It can be H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, phenyl, phenoxy, or R. 1 .

[0059] As an alternative, R is preferred in the fourth, fifth, and / or sixth embodiments. 1 For CH 3-y R y Where R is C2-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C2-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 As an alternative, R is more preferred in the fourth, fifth, and / or sixth embodiments. 1 For CH 3-y R y Wherein R is ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 It can be H, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, phenyl, phenoxy, or R. 1 .

[0060] For Z and R in the fourth, fifth and / or sixth implementation schemes 1 R 2 M 1 M 2 M 3 The preferred, more preferred, and most preferred embodiments of X are the same as those given above for the first and / or second embodiments of the present invention.

[0061] In the fourth embodiment, in step (ii), the solution containing the N-heterocyclic carbene cation according to formula A provided in step (i) may be added to M2M. 1 In X4; or M2M can be used. 1 X4 is added to the solution containing the N-heterocyclic carbene cation according to formula A provided in step (i). M2M 1 X4 can be used in solid or solution form. M2M is preferred. 1 X4 consists of Na2PdCl4 and K2PdCl4.

[0062] In the fifth embodiment, in step (ii), the solution containing the N-heterocyclic carbene cation according to formula B provided in step (i) may be added to M2M. 2 X4 or M 2 In X2; or M2M can be used. 2 X4 or M 2X2 is added to the solution containing the N-heterocyclic carbene cation according to formula B provided in step (i). M2M 2 X4 or M 2 X2 can be used in solid or solution form. M2M is preferred. 2 X4 is either Na₂PtCl₄ or K₂PtCl₄. Preferred M... 2 X2 is ZnCl2.

[0063] In the sixth embodiment, in step (ii), the solution containing the N-heterocyclic carbene cation according to formula C provided in step (i) may be added to MM. 3 In X4; or MM can be used 3 X4 is added to the solution provided in step (i) containing the N-heterocyclic carbene cation according to formula C. MM 3 X4 can be used in solid or solution form. Preferred MM 3 X4 consists of NaAuCl4 and KauCl4.

[0064] Preferably, the solvent of the solution provided in step (i) of the fourth, fifth, and / or sixth embodiments is selected from water, ketones, alcohols, or mixtures thereof. More preferably, the solvent of the solution provided in step (i) of the fourth, fifth, and / or sixth embodiments 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, ethylene glycol, 1-propanol, 2-propanol, 1,2-propanediol, 1,3-propanediol, glycerol, 1-butanol, 2-methyl-1-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-1,2,3-propanetriol, or mixtures thereof. Most preferably, the solvent of the solution provided in step (i) of the fourth, fifth and / or sixth embodiments is a mixture of water and methanol.

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

[0066] The ionic NHC-transition metal compounds of the present invention exhibit excellent catalytic activity in various transition metal-mediated organic reactions, including but not limited to the Suzuki-Miyaura cross-coupling reaction, the Buchwald-Hartwig amination reaction, the ester / amide to amide conversion reaction, and other C- or C-heteroatom coupling reactions. See also Figure 2 Non-limiting examples of the reactions described herein.

[0067] This reaction exhibits similar or better yields compared to state-of-the-art commercially available NHC-transition metal compounds such as, for example, PEPPSI-IPr and NHC-Crotyl-Pd. Therefore, a method for catalyzing transition metal-mediated organic reactions using compounds according to the invention is further provided.

[0068] Therefore, in a seventh embodiment of the present invention, a method for carrying out a transition metal catalytic reaction between a first substrate and a second substrate is provided, wherein the method includes the following steps: (a) Providing a compound according to the first or second embodiment of the invention as a precatalyst in a reaction vessel; (b) Add the first and second substrates to the reaction vessel; and (c) React the first and second substrates at a temperature and time sufficient for transition metal catalysis.

[0069] Preferably, in the seventh embodiment of the invention, the compound provided in step (a) is represented by one of formula I, formula II, or formula III: in: M 1 For Pd; M 2 The material can be Pt or Zn, with Pt being preferred; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl; and And Z as defined in the first or second implementation scheme.

[0070] More preferably, in the seventh embodiment of the present invention, the compound provided in step (a) is represented by formula I: in: M 1 For Pd; X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl; and And Z as defined in the first or second implementation scheme.

[0071] In the seventh implementation plan, for Z and R 1 R 2 M 1 M 2 M 3 The preferred, more preferred, and most preferred embodiments of X are the same as those given above for the first embodiment of the present invention.

[0072] In the seventh implementation plan, for Z and R 1 R 2 M 1 M 2 M 3 The preferred, more preferred, and most preferred embodiments of X are the same as those given above for the second embodiment of the present invention.

[0073] Therefore, in the seventh embodiment, it is preferred that Z represents a selection from... group, in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site.

[0074] Therefore, as an alternative, in the seventh embodiment, it is preferred that Z represents a selection from... group, in: R 1 For CH 3-y R y Where R is C2-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C2-C20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site.

[0075] Most preferably, in the seventh embodiment of the 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 catalytic reaction is selected from C(sp...) 2 )-C(sp 2 Coupling reaction, C(sp) 2 )-N coupling reaction, C(sp 2 )-O coupling reaction, C(sp 2 )-S coupling reaction, C(sp 2 )-P coupling reaction or ester / amide to amide reaction.

[0077] In a more preferred embodiment of the seventh embodiment, the transition metal catalytic reaction is selected from the Suzuki-Miyaura cross-coupling reaction, the Buchwald-Hartwig amination reaction, or the ester / amide to amide reaction.

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

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

[0080] More preferably, when carrying out the Suzuki-Miyaura cross-coupling reaction or the Buchwald-Hartwig amination reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from those substituted with halogens (preferably Br or Cl) and optionally contains one or more C1-C atoms. 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 The C6-C substituents of the group consisting of aryloxy, C3-C9 heteroaryl, C3-C9 heteroaryloxy, F, Br, Cl, I, hydroxyl, nitro and nitrile are... 18 Aromatic compounds.

[0081] Most preferably, when carrying out the Suzuki-Miyaura cross-coupling reaction or the Buchwald-Hartwig amination reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from C6 aromatic compounds substituted with Br or Cl and optionally containing one or more substituents selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C6 aryl, C6 aryloxy, F, Br, Cl, I, hydroxyl, nitro and nitrile.

[0082] Preferably, when performing the ester / amide to amide reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is selected from ester compounds or amide compounds, preferably from R 1 -CO-OR 1 Or R 1 -CO-NR 2 -R 1 , where R 1 It is alkyl or aryl, and R 2 It is an alkyl, aryl, or alkoxycarbonyl group.

[0083] More preferably, when carrying out the ester / amide to amide reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is R. 1 -CO-OR 1 Or R 1 -CO-NR 2 -R 1 , where R 1 For C1-C 10 Alkyl or C6-C 10 Aryl, and R 2 For C1-C 10 Alkyl, C6-C 10 Aryl or alkoxycarbonyl.

[0084] Most preferably, when carrying out the ester / amide to amide reaction, the first substrate provided in step (b) of the method according to the seventh embodiment is R. 1 -CO-OR 1 Or R 1 -CO-NR 2 -R 1 , where R 1 It is a C1-C5 alkyl or C6 aryl, and R 2 It is a C1-C5 alkyl, C6 aryl, or tert-butoxycarbonyl group.

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

[0086] More preferably, when performing the Suzuki-Miyaura cross-coupling reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is optionally containing one or more substrates selected from C1-C2. 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 The C6-C substituents of the group consisting of aryloxy, C3-C9 heteroaryl, C3-C9 heteroaryloxy, F, Br, Cl, I, hydroxyl, nitro and nitrile are... 18 Aromatic boric acid compounds.

[0087] Most preferably, when carrying out the Suzuki-Miyaura cross-coupling reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a C6 aromatic boric acid compound optionally containing one or more substituents selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C6 aryl, C6 aryloxy, F, Br, Cl, I, hydroxyl, nitro and nitrile.

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

[0089] More preferably, when carrying out the Buchwald-Hartwig amination reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a substrate containing one or two C1-C2 atoms. 10 Alkyl, C3-C 10 cycloalkyl and C6-C10 Amine compounds with substituents in the aryl group.

[0090] Most preferably, when the Buchwald-Hartwig amination reaction is carried out, the second substrate provided in step (b) of the method according to the seventh embodiment is an amine compound containing one or two substituents selected from the group consisting of C1-C5 alkyl, C3-C5 cycloalkyl and C6 aryl groups.

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

[0092] More preferably, when carrying out the ester / amide to amide reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is optionally containing one or more substrates selected from C1-C2. 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 The C6-C substituents of the group consisting of aryloxy, C3-C9 heteroaryl, C3-C9 heteroaryloxy, F, Br, Cl, I, hydroxyl, nitro and nitrile are... 18 Aromatic amine compounds.

[0093] Most preferably, when carrying out the ester / amide to amide reaction, the second substrate provided in step (b) of the method according to the seventh embodiment is a C6 aromatic amine compound optionally containing one or more substituents selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy, C6 aryl, C6 aryloxy, F, Br, Cl, I, hydroxyl, nitro and nitrile.

[0094] Preferably, step (c) of the method according to the seventh embodiment is carried out in the presence of an alkali. The preferred alkali is selected from the group consisting of NaOH, KOH, NaOEt, KOEt, NaOtBu, KOtBu, Na2CO3, and K2CO3.

[0095] It should be understood that those skilled in the art can freely combine the preferred, more preferred, and most preferred embodiments related to one of the embodiments of the present invention in any manner as desired.

[0096] definition As used herein, the term "N-heterocyclic carbene," or "NHC" as an abbreviation, 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 NHCs compared to other carbenes is primarily due to the -I and +M effects of adjacent heteroatoms, which increase the electron density of the empty p orbitals on the carbon atom. Besides nitrogen, sulfur or oxygen can also stabilize carbenes. NHCs with an imidazole backbone also gain additional stability through their aromaticity. Free carbenes are typically obtained by deprotonation of imidazole onium salts or corresponding cationic precursors. Strong bases such as, for example, sodium hydride or alkoxides are commonly used. NHCs play an important role as ligands in metal complexes. Due to their strong σ-donor properties and kinetic inertness, they represent popular alternatives to phosphine, especially for transition metal catalysis. Transition metal NHC complexes are generally more temperature-stable and less sensitive to oxidation than phosphine complexes.

[0097] As used in this article, the term "room temperature" refers to the indoor ambient temperature, which is usually considered to be 20°C.

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

[0099] As used in this article, the term "tBu" refers to tert-butyl, which is a branched alkyl group of the formula (-C4H9), which can also be written as (-C(CH3)3).

[0100] As used herein, the term “iPr” refers to isopropyl, which is a branched alkyl group of the formula (-C3H7), which can 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. Alkyl groups can be straight-chain or branched. For example, as used herein, propyl includes n-propyl and isopropyl; butyl includes n-butyl, sec-butyl, isobutyl, and tert-butyl, etc.

[0102] As used herein, the term "cycloalkyl" refers to a cyclic group of a saturated hydrocarbon, such as, but not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl (Cy). It also includes bridged cyclic groups of saturated hydrocarbons, such as, but not limited to, adamantyl.

[0103] As used herein, the term "aryl" refers to an aromatic hydrocarbon group. Aryl groups include, for example, phenyl, biphenyl, naphthyl, anthracene, etc., and their respective substituted forms.

[0104] As used herein, the term "heteroaryl" refers to an aromatic group containing one or more heteroatoms. Preferably, the heteroatoms are selected from O, N, and / or S. Heteroaryl groups include, for example, furanyl, thiopheneyl, pyrroloyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridinyl, pyridazinyl, 1,3,5-triazinyl, indolyl, benzofuranyl, benzoxazolyl, isoquinolinyl, quinolinyl, quinazolinyl, quinoxolinyl, benzoxazinyl, purineyl, pteridinyl, etc., and their respective substituted forms.

[0105] As used herein, "substituted" means that one or more hydrogen atoms of the described compound or functional group are replaced by another functional group or substituent. For example, a substituted phenyl group may include one or more substituents replacing any hydrogen atom on the benzene ring. In some embodiments, there may be one substituent at the ortho, meta, or para positions. In other embodiments, there may be substituents at two ortho positions or two meta positions. In still other embodiments, an optionally substituted phenyl group may include, for example, substituents at the ortho and para positions, or meta and para positions. In some embodiments having multiple substituents, all substituents are identical; in other embodiments having multiple substituents, the substituents are different from each other. Typical substituents include, but are not limited to, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy groups. When a compound or functional group is described as "optionally substituted," the compound or functional group may have one or more substituents, or no substituents.

[0106] The present invention is further illustrated by the following embodiments, which should not be construed as limiting. Those skilled in the art will recognize that various modifications, additions, and alterations can be made to the invention without departing from its spirit and scope. Example

[0107] Synthesis of ionic NHC-transition metal complexes Example 1: Synthesis of ionic NHC-Pd complex 3a-3g MeOH (3 mL) was added to a 20 mL vial containing NHC·HX (X = Cl or BF4, 0.5 mmol, 1.0 equivalent) and a stir bar. To prepare a palladium solution, Na2PdCl4 (147 mg, 0.5 mmol, 1.0 equivalent) and H2O (3 mL) were added to a separate 20 mL vial, and this solution was added to the previously prepared MeOH slurry over 5 minutes at room temperature. The resulting apricot-colored slurry was allowed to be stirred at the same temperature for another hour. After the reaction was complete, H2O (15 mL) was added to the reaction mixture, and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 mL) and Et2O (25 mL), collected, and dried to give the desired apricot-colored complex 3a-3 g.

[0108] Complex 3a: Complex 3a ([IPr-H]2Pd2Cl6) was obtained in 92% yield using IPr·HCl (1,3-bis(2,6-diisopropylphenyl)imidazolium chloride) according to the general procedure.

[0109] 1 H NMR (500 MHz, CD2Cl2) 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).

[0110] Complex 3b: Complex 3b ([IPr*-H]2Pd2Cl6) was obtained in 88% yield using IPr*·HCl (N,N'-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazolium chloride) according to the general procedure.

[0111] 1 H NMR (500 MHz, CD2Cl2) 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, J =7.1, 1.9 Hz, 8H), 5.50 (d, J= 1.5 Hz, 2H), 5.20 (s, 4H), 2.27 (s, 6H).

[0112] Complex 3c: Complex 3c ([IPr*OMe-H]2Pd2Cl6), using IPr*OMe·HBF4 (N,N'-bis(2,6-bis(diphenylmethyl)-4-methoxyphenyl)imidazolium tetrafluoroborate) according to the general procedure, in 80% yield.

[0113] 1 H NMR (500 MHz, CD2Cl2) 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 = 1.5Hz, 2H), 5.04 (s, 4H), 3.57 (s, 6H).

[0114] 3D of the coordination compound: 3d complex ([IPr) # -H]2Pd2Cl6), using IPr#·HCl (1,3-bis(2,4,6-tris ...

[0115] 1 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, J = 6.9, 1.9 Hz, 8H), 6.90 – 6.81 (m, 18H), 5.59 (s, 2H), 5.14 (s, 4H).

[0116] Complex 3e: The complex 3e ([SIPr-H]2Pd2Cl6) was obtained as a single crystal suitable for crystallographic analysis at room temperature by passing it through pentane / acetone using SIPr·HCl (1,3-bis(2,6-diisopropylphenyl)imidazoline onion chloride) according to a general procedure, with a yield of 91%.

[0117] 1 H NMR (500 MHz, CD2Cl2) 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 = 6.7Hz, 12H), 1.25 (d, J = 6.9 Hz, 12H).

[0118] Complex 3f: Complex 3f ([IPent-H]2Pd2Cl6) was obtained in 93% yield using IPent·HCl (1,3-bis(2,6-di(3-pentyl)phenyl)imidazolium chloride) according to the general procedure.

[0119] 1 H NMR (500 MHz, CD2Cl2) δ 8.10 (t, J = 1.7 Hz, 1H), 8.02 (d, J = 1.6 Hz, 2H), 7.68 (t, J = 7.8 Hz, 2H), 7.35 (d, J = 7.9 Hz, 4H), 1.93 (tt, J = 8.3, 6.0 Hz,5H), 1.84 – 1.72 (m, 9H), 1.72 – 1.59 (m, 7H), 0.91 (t, J = 7.4 Hz, 12H), 0.77(t, J = 7.4 Hz, 12H).

[0120] 3g of complex: 3 g of the complex ([ICy-H]2Pd2Cl6) was crystallized in pentane / acetone at room temperature using ICy·HBF4 (1,3-dicyclohexylimidazolium tetrafluoroborate) according to a standard procedure, yielding single crystals suitable for crystallographic analysis in 63% yield.

[0121] 1 H NMR (500 MHz, CD2Cl2) 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).

[0122] Example 2: Synthesis of ionic NHC-Pt complex 4b MeOH (3 mL) was added to a 20 mL vial containing 1a (IPr·HCl) (213 mg, 0.5 mmol, 2.0 equivalent) and a stir bar. To prepare a platinum solution, 4a (K₂PtCl₄) (104 mg, 0.25 mmol, 1.0 equivalent) and H₂O (3 mL) were added to a separate 20 mL vial and added to the previously prepared MeOH solution over 5 minutes at room temperature. The resulting slurry was allowed to be stirred at the same temperature for another hour. After the reaction was complete, H₂O (15 mL) was added to the reaction mixture, and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H₂O (20 mL) and Et₂O (25 mL), collected, and dried to give the desired complex 4b ([IPr-H]₂PtCl₄).

[0123] 1 H NMR (500 MHz, CD2Cl2) 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, J = 6.9 Hz, 13H).

[0124] Example 3: Synthesis of ionic NHC-Zn complex 5b MeOH (3 mL) was added to a 20 mL vial containing 1e (SIPr·HCl) (214 mg, 0.5 mmol, 2.0 equivalent) and a stir bar. To prepare a zinc solution, 5a (ZnCl2) (34 mg, 0.25 mmol, 1.0 equivalent) and H2O (3 mL) were added to a separate 20 mL vial and added to the previously prepared MeOH solution over 5 minutes at room temperature. The resulting slurry was allowed to be stirred at the same temperature for another hour. After the reaction was complete, H2O (15 mL) was added to the reaction mixture, and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 mL) and Et2O (25 mL), collected, and dried to give the desired complex 5b ([SIPr-H]2ZnCl4).

[0125] 1 H NMR (500 MHz, CDCl3) 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, J = 6.8, 2.0 Hz, 12H), 1.17 (d, J = 6.8 Hz, 12H).

[0126] Example 4: Synthesis of ionic NHC-Au complex 6b MeOH (3 mL) was added to a 20 mL vial containing 1e (SIPr·HCl) (214 mg, 0.5 mmol, 1.0 equivalent) and a stir bar. To prepare a gold solution, 6a (KauCl4) (189 mg, 0.5 mmol, 1.0 equivalent) and H2O (3 mL) were added to a separate 20 mL vial and added to the previously prepared MeOH solution over 5 minutes at room temperature. The resulting slurry was allowed to be stirred at the same temperature for another hour. After the reaction was complete, H2O (15 mL) was added to the reaction mixture, and the resulting precipitate was collected by vacuum filtration. The solid was further washed with H2O (20 mL) and Et2O (25 mL), collected, and dried to give the desired complex 6b ([SIPr-H]AuCl4).

[0127] 1 H NMR (500 MHz, CD2Cl2) δ 7.97 (s, 1H), 7.56 (t, J = 7.8 Hz, 2H), 7.36(d, J = 7.8 Hz, 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, J = 6.9 Hz, 12H).

[0128] Applications of ionic NHC-transition metal complexes in transition metal-mediated organic reactions Example 5: Suzuki-Miyaura cross-coupling reaction In a 4 mL vial containing various pre-catalysts (1.0 mol%), KOH (56 mg, 1.0 mmol, 2.0 equivalent), and a stir bar, 1 mL of 2-MeTHF, 0.5 mmol, 1.0 equivalent of 2-chlorotoluene, and 0.75 mmol, 1.5 equivalent of 2,6-dimethyl-phenylboronic acid were added. The resulting mixture was allowed to be stirred at 40 °C for 90 min. The reaction yield was determined by GC and is shown in Table 1 below.

[0129] Table 1: Reactions in Example 5 .

[0130] The structures of the known complexes (IPr)Pd(cin)Cl

[13] , PEPPSI-Ipr (CAS: 905459-27-0) and (IPr)Pd(ind)Cl[2b],

[13] used in Example 5 are as follows: .

[0131] Example 6: Suzuki-Miyaura cross-coupling reaction 2-MeTHF (3 mL), 2-chloro-m-xylene (0.5 mmol, 1.0 equivalent), and 2,4,6-trimethyl-phenylboronic acid (0.75 mmol, 1.5 equivalent) were added to 4 mL vials containing various pre-catalysts (2.0 mol%), KOH (56 mg, 1.0 mmol, 2.0 equivalent), and a stir bar. The resulting mixture was allowed to be stirred at 60 °C for 24 hours. The conversion was determined by GC and is shown in Table 2 below.

[0132] Table 2: Reactions in Example 6 .

[0133] Example 7: Suzuki-Miyaura cross-coupling reaction In a 4 mL vial containing complex 3a ([IPr-H]2Pd2Cl6) (3.2 mg, 1.0 mol%), KOH (56 mg, 1.0 mmol, 2.0 equivalent), and a stir bar, 2-MeTHF (1 mL), Ar / Het-Cl (0.5 mmol, 1.0 equivalent), and R¹-B(pin) (0.75 mmol, 1.5 equivalent) were added. The resulting mixture was allowed to be stirred at 55 °C for 5 hours. After the reaction was complete, all volatiles were removed under vacuum, and the residue was further purified by silica gel column chromatography to obtain the desired product as shown below.

[0134] Product 7.1 2,2',6-Trimethyl-1,1'-Biphenyl: 81% yield. 1 H NMR (500 MHz, CDCl3) 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).

[0135] Product 7.2 2-(2,6-Dimethylphenyl)-3-methylpyridine: 91% yield. 1 H NMR (500 MHz, CDCl3) 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).

[0136] Product 7.3 2,2',6,6'-Tetramethyl-1,1'-Biphenyl: 84% yield, using complex 3b ([IPr*-H]2Pd2Cl6, 1.0 mol%) as catalyst. 1 H NMR (500 MHz, CDCl3) 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).

[0137] Example 8: Buchwald-Hartwig amination reaction In a 4 mL vial containing complex 3b([IPr*-H]2Pd2Cl6) (5.6 mg, 0.5 mol%), NaOtBu (144 mg, 1.5 mmol, 1.5 equivalents), and a stir bar, 2-MeTHF (1 mL), Ar-Cl (1.0 mmol, 1.0 equivalents), and a primary or secondary amine (1.5 mmol, 1.5 equivalents) were added. The resulting mixture was allowed to be stirred at 55 °C for 5 hours. After the reaction was complete, all volatiles were removed under vacuum, and the residue was further purified by silica gel column chromatography to obtain the desired product as shown below.

[0138] Product 8.1 N-(2,6-dimethylphenyl)-2,6-dimethylaniline: 97% yield. 1 H NMR (500 MHz, CDCl3) δ6.98 (d, J = 7.4 Hz, 4H), 6.84 (t, J = 7.4 Hz, 2H), 4.80 (s, 1H), 2.01 (s, 12H).

[0139] Product 8.2 N-Cyclobutyl-4-quinolinamine: 90% yield. 1 H NMR (500 MHz, CDCl3) δ 9.46 (d, J = 5.3Hz, 1H), 8.91 (dd, J = 8.5, 1.3 Hz, 1H), 8.69 (dd, J = 8.4, 1.3 Hz, 1H), 8.54(ddd, J = 8.3, 6.8, 1.4 Hz, 1H), 8.34 (ddd, J = 8.3, 6.8, 1.3 Hz, 1H), 7.25 (d, J =5.3 Hz, 1H), 6.20 (d, J = 5.1 Hz, 1H), 5.11 – 4.95 (m, 1H), 3.54 – 3.39 (m, 2H), 3.01 – 2.72 (m, 4H).

[0140] Product 8.3 N,3-Dimethyl-N-phenyl-2-pyridinamide: 87% yield. 1 H NMR (500 MHz, CDCl3) 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, J = 7.4, 4.8 Hz, 1H), 6.90 (tt, J= 7.3, 1.1 Hz, 1H), 6.79 – 6.74(m, 2H), 3.42 (s, 3H), 1.93 (s, 3H).

[0141] Yield 8.4 N-Butyl-3-methyl-2-pyridinamide: 93% yield. 1 H NMR (500 MHz, CDCl3) δ 8.02 (dt, J =5.2, 1.2 Hz, 1H), 7.19 (ddq, J = 7.1, 1.8, 0.9 Hz, 1H), 6.49 (dd, J = 7.1, 5.1Hz, 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, J = 7.3 Hz, 3H).

[0142] Product 8.5 N,N-Dibutyl-3-methyl-2-pyridinamide: 91% yield. 1 H NMR (500 MHz, CDCl3) δ 8.14(ddd, J = 4.9, 1.9, 0.7 Hz, 1H), 7.36 (ddt, J = 7.4, 1.6, 0.8 Hz, 1H), 6.78 (dd, J = 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, J = 14.7, 7.4 Hz, 4H), 0.87 (t, J = 7.4 Hz, 6H).

[0143] Product 8.6 N-(1,1-dimethylethyl)-3-methyl-2-pyridinamine: 94% yield (separated as HCl salt).1 H NMR (500 MHz, CDCl3) δ 14.07 (d, J = 27.5 Hz, 1H), 8.46 (t, J = 7.1 Hz, 1H), 7.61 (d, J = 7.1 Hz, 1H), 6.77 (qd, J = 6.8, 5.5, 2.1 Hz, 1H), 5.29 (d, J = 24.1 Hz, 1H), 2.26 (d, J = 2.6 Hz, 3H), 1.75 – 1.68 (m, 9H).

[0144] Example 9: Ester-to-amide reaction DME (1 mL) was added to a 4 mL vial containing complex 3b([IPr*-H]2Pd2Cl6) (8.4 mg, 3 mol%), K2CO3 (104 mg, 0.75 mmol, 1.5 equivalents), p-methoxyaniline (62 mg, 0.5 mmol, 2.0 equivalents), phenyl benzoate (0.25 mmol, 1.0 equivalents), and a stir bar. The resulting mixture was stirred at 100 °C for 15 hours. After the reaction was complete, all volatiles were removed under vacuum, and the residue was further purified by silica gel column chromatography to obtain the desired product.

[0145] 4'-Methoxybenzoylaniline: 84% yield. 1 H NMR (500 MHz, CDCl3) δ 7.86 (dt, J =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).

[0146] Example 10: Amide to Amide Conversion Reaction DME (1 mL) was added to a 4 mL vial containing complex 3b([IPr*-H]2Pd2Cl6) (8.4 mg, 3 mol%), K2CO3 (104 mg, 0.75 mmol, 1.5 equivalents), p-methoxyaniline (62 mg, 0.5 mmol, 2.0 equivalents), tertiary amide (0.25 mmol, 1.0 equivalents), and a stir bar. The resulting mixture was stirred at 100 °C for 15 hours. After the reaction was complete, all volatiles were removed under vacuum, and the residue was further purified by silica gel column chromatography to obtain the desired product.

[0147] 4'-Methoxybenzoylaniline: 84% yield. 1 H NMR (500 MHz, CDCl3) δ 7.86 (dt, J =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).

[0148] The embodiments provided herein are in no way intended to limit the scope of the invention as set forth in the claims.

[0149] References [1] CCC Johansson Seechurn, MO Kitching, TJ Colacot, V.Snieckus, Angew. Chem. Int. Ed. 2012, 51 , 5062–5085. [2] (a) SJ Firsan, V. Sivakumar, TJColacot, Chem. Rev. 2022, 122 ,16983-17027; (b) JP Norman, NG Larson, SR Neufeldt, ACS Catal. 2022, 12 ,8822-8828. [3] GC Fortman, SP Nolan, Chem. Soc. Rev. 2011, 40 , 5151-5169. [4] DP Hruszkewycz, D. Balcells, LM Guard, N. Hazari, M. Tilset, J. Am. Chem. Soc.2014, 136 , 7300-7316. [5] PR Melvin, A. Nova, D. Balcells, W. Dai, N. Hazari, DPHruszkewycz, HP Shah, MT Tudge, ACS Catal. 2015, 5 , 3680-3688. [6] N. Sivendran, N. Pirkl, Z. Hu, A. Doppiu, LJ Gooßen, Angew. Chem. Int. Ed. 2021, 60 , 25151-25160. [7] (a) EAB Kantchev, CJ O'Brien, MG Organ, Angew. Chem. Int. Ed. 2007, 46 , 2768-2813; (b) A. Khadra, S. Mayer, MG Organ, Chem. Eur. J. 2017, 23 , 3206-3212. [8] (a) WO 2021 / 142281 A1; (b) WO 2021 / 142289 A1. [9] (a) N. Marion, SP Nolan, Acc. Chem. Res. 2008, 41 , 11 , 1440-1449;(b) SG Guillet, VA Voloshkin, M. Saab, M. Belish, K. van Hecke, F. Nahra,SP Nolan, Chem. Common. 2020, 56 , 5953-5956.

[10] F. Schroeter, J. Soellner, T. Strassner, Chem. Eur. J. 2019, 25 ,2527-2537.

[11] N. Marion, SP Nolan, Chem. Soc. Rev. 2008, 37 , 1776-1782.

[12] O. Santoro, F. Nahra, DB Cordes, AMZ Slawin, SP Nolan,CSJ Cazin, J. Mol. Catal. A: Chem. 2016, 423 , 85-91.

[13] SR Vemula, MR Chhoun, GR Cook, Molecules, 2019, 24 , 215。

Claims

1. A compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, The N-heterocyclic carbene cation is: in: Indicates a single bond or a double bond; Z indicates that it is selected from group, in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site; and The transition metal halide anion comprises one or more transition metal atoms and one or more halogen atoms; The condition is that the following compounds are not included: 。 2. The compound according to claim 1, wherein... R 1 For CH 3-y R y Where R is C1-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C1-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 .

3. The compound according to claim 1 or 2, wherein... R 1 For CH 3-y R y Wherein R is methyl, ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 It can be H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, phenyl, phenoxy, or R. 1 .

4. A compound comprising one or more N-heterocyclic carbene cations and one or more transition metal halide anions, The N-heterocyclic carbene cation is: in: Indicates a single bond or a double bond; Z indicates that it is selected from group, in: R 1 For CH 3-y R y Where R is C2-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C2-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the binding site; and 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, wherein... R 1 For CH 3-y R y Where R is C2-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C2-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 .

6. The compound according to claim 4 or 5, wherein R 1 For CH 3-y R y Wherein R is ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 It can be H, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, phenyl, phenoxy, or R. 1 .

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, and 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 Cl and Br, and 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: in: M 1 For Pd; M 2 The material can be Pt or Zn, with Pt being preferred; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and 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: in: M 1 For Pd; M 2 The material can be Pt or Zn, with Pt being preferred; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl; and And Z as defined in claim 1 or 4.

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

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

13. A method for synthesizing a compound according to formula I, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula A; as well as (ii) Mix the solution provided in step (i) with M2M 1 The X4 reaction yields the compound according to formula I: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 1 For Pd; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

14. A method for synthesizing a compound according to formula II, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula B; as well as (ii) Mix the solution provided in step (i) with M2M 2 X4 or M 2 The X2 reaction yields the compound according to formula II: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 2 It can be Pt or Zn, with Pt preferred; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

15. A method for synthesizing a compound according to formula III, wherein the method comprises the following steps: (i) Provide a solution containing an N-heterocyclic carbene cation according to formula C; as well as (ii) Mix the solution provided in step (i) with MM 3 The X4 reaction yields the compound according to formula III: in: Indicates a single bond or a double bond; Z represents in: R 1 For CH 3-y R y Where R is C1-C 20 Alkyl or C6-C 14 Aryl group, and y is 1, 2 or 3, preferably 2; R 2 For H, C1-C 20 Alkyl, C1-C 20 Alkoxy, C6-C 14 Aryl, C6-C 14 aryloxy or R 1 ;and Indicates the 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, and most preferably Na; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl.

16. The method according to any one of claims 13 to 15, wherein: R 1 For CH 3-y R y Where R is C1-C 10 Alkyl or C6-C 10 Aryl group, and y is 1, 2 or 3, preferably 2; and R 2 For H, C1-C 10 Alkyl, C1-C 10 Alkoxy, C6-C 10 Aryl, C6-C 10 aryloxy or R 1 .

17. The method of claim 16, wherein R 1 For CH 3-y R y Wherein R is methyl, ethyl, n-propyl, isopropyl, or phenyl, and y is 1, 2, or 3, preferably 2; and R 2 It can be H, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, phenyl, phenoxy, or R. 1 .

18. A method for carrying out a transition metal-catalyzed reaction between a first substrate and a second substrate, wherein the method comprises the following steps: (a) The compound according to one or more of claims 1 to 10 is provided as a precatalyst in the reaction vessel; (b) Add the first substrate and the second substrate to the reaction vessel; as well as (c) React the first substrate and the second substrate at a temperature and time sufficient for a transition metal catalytic reaction to occur.

19. The method of claim 18, wherein the compound provided in step (a) is represented by one of formula I, formula II, or formula III: in: M 1 For Pd; M 2 The material can be Pt or Zn, with Pt being preferred; M 3 For Au; and X is a halogen atom, preferably F, Cl, Br or I, more preferably Cl or Br, and most preferably Cl; and And Z as defined in claim 1 or 4.

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

21. The method according to any one of claims 18 to 20, wherein the transition metal catalytic reaction is selected from C(sp...) 2 )-C(sp 2 Coupling reaction, C(sp) 2 )-N coupling reaction, C(sp 2 )-O coupling reaction, C(sp 2 )-S coupling reaction, C(sp 2 )-P coupling reaction or ester / amide to amide reaction.

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

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