Triarylmethane compound with high optical purity as well as preparation method and application of triarylmethane compound

Abstract

The invention relates to a triarylmethane compound with high optical purity as well as a preparation method and application of the triarylmethane compound. Specifically, according to the method, monovalent rhodium / chiral diene ligand and monovalent gold are used as catalysts, and selective preparation of the chiral triarylmethane compound is realized through asymmetric 1, 4-addition reaction of an aryl rhodium species obtained through metallization of arylboronic acid on an in-situ generated aza-o-methylene heteroaryl quinone intermediate. According to the method, the catalyst and the ligand are simple to prepare, the reaction condition is mild, the operation is simple and convenient, the substrate universality is good, and the chiral triarylmethane compound containing one, two and three heteroaromatic rings can be obtained with good yield and excellent enantioselectivity.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemistry, and in particular, the present application relates to asymmetric 1,4-addition reaction catalyzed by monovalent rhodium and monovalent gold in cooperation, and a method for preparing chiral triarylmethane compounds. BACKGROUND

[0002] Michael addition reaction is one of the most effective methods for constructing carbon-carbon bond. In organic synthesis, the development of asymmetric Michael addition reaction involving transition metal catalysis and aryl boron reagent is relatively mature. Among them, 1,4 / 1,6-addition reaction of p-ortho-methylenephenol can prepare triarylmethane compounds. In the past ten years, there are mainly four strategies for synthesizing triarylmethane compounds: 1) Lewis acid or Bronsted acid catalyzed Friedel-Crafts arylation reaction; 2) transition metal catalyzed direct arylation reaction; 3) transition metal catalyzed cross-coupling reaction; 4) Bronsted acid or transition metal catalyzed addition reaction of p-ortho-methylenephenol. Among them, the strategy of using small organic molecules (chiral Bronsted acid) catalysis can synthesize chiral triarylmethane compounds, and there are some successful reports in the literature, but this method usually needs to introduce specific groups as hydrogen bond acceptors in the substrate molecule to achieve the stereochemical control of the reaction (Li, X.G.; Duan, M.; Deng, Z.; Shao, Q.; Chen, M.; Zhu, H.; Houk, K.N.; Sun, J.W. Nature Catalysis. 2020, 3, 1010); it is very challenging to efficiently distinguish three aryl groups and expand the tolerance of functional groups in aryl groups to achieve stereochemical control. At present, there are only a few reports on the construction of chiral triarylmethane compounds using transition metal catalysis strategy, and the substrates are limited: ((a) Huang, Y.; Hayashi, T. J. Am. Chem. Soc. 2015, 137, 7556; (b) Lou, Y.; Cao, P.; Jia, T.; Zhang, Y.; Wang, M.; Liao, J. Angew. Chem., Int. Ed. 2015, 54, 12134; (c) Pan, T.; Shi, P.; Zhou, D.-G.; Zeng, Y.-L.; Chu, W.-D.; He, L.; Liu, Q.-Z.; Fan, C.-A.; Org. Lett. 2019, 21, 6397).

[0003] Due to its special three-dimensional structure, triarylmethane compounds are often found in some drug molecules and staining agents, such as glucocorticoid receptor antagonists and retinoid activity modulators ((a) Meier, H.; Kim, S. Eur. J. Org. Chem. 2001, 1163; (b) Brasselet, S.; Cherioux, F.; Audebert, P.; Zyss, J. Chem. Mater. 1999, 11, 1915; (c) Palchaudhuri, R.; Nesterenko, V.; Hergenrother, J. J. Am. Chem. Soc. 2008, 130, 10274; (d) Long, Y. Q.; Jiang, X. H.; Dayam, R.; Sanchez, T.; Shoemaker, R.; Sei, S.; Neamati, N. J. Med. Chem. 2004, 47, 2561.).

[0004] Therefore, there is an urgent need in the art to develop a practical method for transition metal-catalyzed, efficient and highly selective preparation of chiral triarylmethane compounds with high optical purity. SUMMARY

[0005] The purpose of the present application is to provide a method for efficient, highly selective and practical preparation of chiral triarylmethane compounds with high optical purity and its use.

[0006] Another purpose of the present application is to provide the use of chiral triarylmethane compounds with high optical purity in the synthesis of drugs.

[0007] In the first aspect of the present application, a method for preparing chiral triarylmethane compounds with high optical purity is provided, comprising the steps of:

[0008] In an organic solvent, in the presence of a monovalent gold catalyst, the acetylene amide compound of formula 1 generates an azo-ortho-methylene heteroaryl quinone intermediate in situ, and then in the presence of a monovalent rhodium / diene ligand, undergoes asymmetric 1,4-addition reaction with aryl boronic acid of formula 2, to obtain chiral triarylmethane compounds of formula 3 or formula ent-3;

[0009]

[0010] In the formula,

[0011] Ar 1 is selected from: substituted or unsubstituted C 6-30 aryl, substituted or unsubstituted 5-30 membered heteroaryl; wherein the substitution of Ar 1 means that one or more H on the group is replaced by a group selected from the group consisting of halogen, C1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 6-14 Aryl, hydroxyl; the halogen is F, Cl, Br, or I;

[0012] Ar 2 Selected from: substituted or unsubstituted C 6-30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl; wherein, the Ar 2 Substitution refers to the substitution of one or more H atoms on a group by a group selected from the following group: halogens, C atoms, and H atoms. 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl group; the halogen is F, Cl, Br, or I;

[0013] Ar 3 Selected from: substituted or unsubstituted C 6-10 Aryl; wherein, the Ar 3 Substitution refers to the substitution of one or more H atoms on a group by a group selected from the following group: C 1-6 Alkoxy;

[0014] R 1 Selected from: substituted or unsubstituted C 1-6 alkylsulfonyl, substituted or unsubstituted benzenesulfonyl, wherein the R 1 Substitution refers to having one or more substituents selected from the group consisting of: C 1-6 Alkyl, C 1-6 Alkoxy;

[0015] The monovalent rhodium and chiral diene ligands form a complex before being added to the reaction system, or are added to the reaction solution separately and form a complex in situ.

[0016] In another preferred example, Ar 1 Selected from: substituted or unsubstituted C 6-14 Aryl, substituted or unsubstituted 5-membered heteroaryl;

[0017] In another preferred example, Ar 1 Selected from: substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted phenanthryl, substituted or unsubstituted thiophene, substituted or unsubstituted furanyl; wherein substitution refers to one or more H atoms on the group being substituted by groups selected from the group consisting of: halogens, C 1-4 Alkyl, C 1-4 Haloalkyl, C 1-4 Alkoxy, C 6-14 Aryl, hydroxyl, or combinations thereof; the halogen is F, Cl, Br, or I.

[0018] In another preferred example, Ar 1 Selected from the following group: phenyl, methyl-substituted phenyl, dimethyl-substituted phenyl, methoxy-substituted phenyl, dimethoxy-substituted phenyl, tert-butyl-substituted phenyl, hydroxy-substituted phenyl, fluorophenyl, chlorophenyl, bromophenyl, trifluoromethyl-substituted phenyl, phenyl-substituted phenyl, naphthyl, phenanthryl, thiophene, furanyl;

[0019] In another preferred example, Ar 2 Selected from: substituted or unsubstituted C 6-10 Aryl, substituted or unsubstituted 5-7 membered heteroaryl (including 5-, 6- and 7-membered heteroaryl);

[0020] In another preferred example, Ar 2 Selected from: substituted or unsubstituted phenyl groups, substituted or unsubstituted naphthyl groups, substituted or unsubstituted 5-7 membered heteroaryl groups (including furanyl and thiopheneyl);

[0021] In another preferred example, Ar 2 Selected from the following group: phenyl, methyl-substituted phenyl, methoxy-substituted phenyl, chlorophenyl, bromophenyl, naphthyl, thiophene;

[0022] In another preferred example, Ar 3 Selected from: substituted or unsubstituted phenyl groups; wherein, the substitution refers to one or more H atoms on the group being substituted by groups selected from the group consisting of: C 1-6 Alkoxy (preferably C) 1-4 Alkyl groups).

[0023] In another preferred example, Ar 3 Selected from the following group: phenyl, methoxy-substituted phenyl.

[0024] In another preferred embodiment, R 1 Selected from: substituted or unsubstituted benzenesulfonyl groups; wherein, the R 1 Substitution refers to having one or more substituents selected from the group consisting of: C 1-6 Alkyl, C 1-6 Alkyl group.

[0025] In another preferred embodiment, R 1 Selected from the following group: p-methylbenzenesulfonyl, p-nitrobenzenesulfonyl.

[0026] In another preferred embodiment, the compound of formula 1 is selected from the group consisting of:

[0027]

[0028]

[0029] In another preferred embodiment, the compound of formula 2 is selected from the group consisting of:

[0030]

[0031] In another preferred embodiment, the compound of formula 3 or formula ent-3 is selected from the group consisting of:

[0032]

[0033] In another preferred embodiment, the chiral diene ligand has the following structural formula:

[0034] or

[0035] R 2 R 3 Each is independently either substituted or unsubstituted C 6-30 Aryl, substituted or unsubstituted metal complexes of C 6-30 Aryl, of which R 2 and R 3 The groups can be the same or different; the substitution refers to one or more H atoms being replaced by groups selected from the group consisting of: halogens, C atoms, and so on. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkoxy groups, nitro groups, -CON i Pr2.

[0036] In another preferred embodiment, R 2 R 3 Each is independently either substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted metal complexes of C 6-20 Aryl.

[0037] In another preferred embodiment, R 2 R 3 Each is independently either substituted or unsubstituted C 6-14 Aryl.

[0038] In another preferred embodiment, R 2 R 3 Each can be independently substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted anthraquinyl, substituted or unsubstituted phenanthryl, or substituted or unsubstituted ferroceneyl.

[0039] In another preferred embodiment, R 2 R 3 They can be the same or different.

[0040] In another preferred embodiment, R 2R is an unsubstituted phenyl group. 3 For substituted phenyl; or R 2 R is an unsubstituted phenyl group. 3 It is a substituted phenyl group.

[0041] In another preferred embodiment, R 2 and R 2 Same, 9-phenotype.

[0042] In another preferred embodiment, the chiral diene ligand is one or more selected from the group consisting of:

[0043]

[0044] In another preferred embodiment, the monovalent rhodium catalyst is selected from the group consisting of [Rh(C2H4)2Cl]2, [Rh(C2H4)2OH]2, [Rh(coe)2Cl]2, [Rh(coe)2OH]]2, [Rh(C2H4)2OMe]2, [Rh(coe)2OMe]2, or combinations thereof;

[0045] The monovalent gold catalyst is selected from the group consisting of PPh3AuCl, PPh3AuPF6, PPh3AuOTf, PPh3AuBF4, or combinations thereof.

[0046] In another preferred embodiment, the method further includes one or more features selected from the group consisting of:

[0047] (1) The amount of the monovalent rhodium catalyst is 0.1 to 20 mol% based on the amount of compound of Formula 1;

[0048] (2) The amount of the chiral diene ligand is 0.12 to 22 mol% based on the amount of compound of Formula 1;

[0049] (3) The amount of the monovalent gold catalyst is 1.0 to 10 mol% based on the amount of compound of Formula 1;

[0050] (4) The organic solvent is C 1-4 Halogenated alkanes, C 6-8 Aromatic hydrocarbons or their analogues, oxaalkane or oxacycloalkanes, or combinations thereof; the C 1-4 The haloalkane is selected from the group consisting of: dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dichloropropane, 1-chlorobutane, or combinations thereof; the C... 6-8 Aromatic hydrocarbons or their analogues are selected from the group consisting of toluene, chlorobenzene, xylene, or combinations thereof; the oxaalkane or oxacycloalkane is selected from the group consisting of diethyl ether, tetrahydrofuran, 1,4-dioxane, or combinations thereof.

[0051] (5) The reaction temperature is 0–80℃;

[0052] (6) The reaction time is 0.1–72 hours.

[0053] A second aspect of the invention provides compounds as shown in Formula 3 or Formula ent-3:

[0054] or

[0055] In the formula,

[0056] Ar 1 Ar 2 Ar 3 R 1 As defined in the first aspect of the invention; preferably, R 1 It is an aryl-substituted sulfonyl group; more preferably, R 1 It is p-toluenesulfonyl.

[0057] In another preferred embodiment, the compound is selected from the group consisting of:

[0058]

[0059] A third aspect of the invention provides the use of compounds of formula 3 or ent-3 for the preparation of chiral synthetic building blocks, pharmaceutical intermediates, or active compounds as shown in the following formula:

[0060]

[0061] Among them, Ar 1 Ar 2 Ar 3 R 1 As defined in the first aspect of this invention.

[0062] A fourth aspect of the present invention provides a method for preparing a compound represented by formula 4-1, characterized in that it comprises the following steps:

[0063]

[0064] The structure shown in Formula 3-1 is used to undergo a substitution reaction with 4-bromo-1-butene to form a chiral triarylmethane compound 4-1.

[0065] Among them, Ar 1 Ar 2 Ar 1 R 1 The definition is as described in the first aspect of the present invention.

[0066] In another preferred embodiment, the method is carried out in the presence of an alkali, preferably in the presence of K2CO3.

[0067] In another preferred embodiment, the method is carried out in acetone solvent.

[0068] A fifth aspect of the present invention provides a method for preparing a compound represented by Formula 5-1, characterized in that the method comprises the steps of:

[0069] (1) Preparation of compound 4-1 using the method as described in the fourth aspect of the present invention; and

[0070]

[0071] (2) The 4-1 compound was subjected to an intramolecular DA reaction to obtain compound 5-1.

[0072] In another preferred embodiment, the method in step (2) is carried out in toluene solvent.

[0073] A sixth aspect of the present invention provides a method for preparing a compound represented by formula 6-1, characterized in that it comprises the following steps:

[0074] (1) Preparation of compound 5-1 using the method as described in the fifth aspect of the present invention; and

[0075]

[0076] (2) The 5-1 compound was deprotected and then oxidized to obtain compound 6-1.

[0077] In another preferred embodiment, the method in step (2) is performed in the presence of Red-Al.

[0078] In another preferred embodiment, the method in step (2) is carried out in toluene solvent.

[0079] A seventh aspect of the present invention provides a method for preparing a compound represented by formula 7-1, characterized in that the method comprises the steps of:

[0080]

[0081] Compound 3-1 was subjected to oxidative ring-opening to obtain compound 7-1.

[0082] In another preferred embodiment, the method is performed in the presence of m-CPBA.

[0083] In another preferred embodiment, the method is carried out in a DCM solvent.

[0084] An eighth aspect of the present invention provides a method for preparing a compound represented by formula 8-1, characterized in that the method comprises the steps of:

[0085] (1) Preparation of compound 7-1 using the method as described in the seventh aspect of the present invention; and

[0086]

[0087] (2) The condensation-cyclization reaction of the 7-1 compound was carried out to obtain compound 8-1.

[0088] In another preferred embodiment, the method in step (2) is carried out in the presence of hydrazine hydrate.

[0089] In another preferred embodiment, the method in step (2) is carried out in a DMF solvent.

[0090] A ninth aspect of the present invention provides a method for preparing a compound represented by formula 9-1, characterized in that the method comprises the steps of:

[0091] (1) Preparation of compound 7-1 using the method as described in the seventh aspect of the present invention; and

[0092]

[0093] (2) The 7-1 compound was reduced to obtain compound 9-1.

[0094] In another preferred embodiment, the method in step (2) uses HSiCl3 as a reducing agent.

[0095] In another preferred embodiment, the method in step (2) uses triphenylphosphine oxide as a catalyst.

[0096] In another preferred embodiment, the method in step (2) is carried out in a 1,2-dichloroethane solvent.

[0097] A tenth aspect of the present invention provides a method for preparing a compound represented by formula 10-1, characterized in that the method comprises the steps of:

[0098] (1) Preparation of compound 9-1 using the method as described in the ninth aspect of the present invention; and

[0099]

[0100] (2) The 9-1 compound was reduced to obtain compound 10-1.

[0101] In another preferred embodiment, the method in step (2) is carried out in the presence of hydrazine hydrate.

[0102] In another preferred embodiment, the method in step (2) is carried out in a solvent selected from the group consisting of EtOH, DCM, or a combination thereof.

[0103] The eleventh aspect of the present invention provides a method for preparing a compound represented by formula 11-1, characterized in that it includes the following steps:

[0104]

[0105] The protecting group of compound 3-1 was removed to obtain compound 11-1.

[0106] In another preferred embodiment, the method is carried out in the presence of methyl bromoacetate and K2CO3.

[0107] In another preferred embodiment, the method is carried out in a DMF solvent.

[0108] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Detailed Implementation

[0109] Through extensive and in-depth research, the inventors discovered that by using a monovalent rhodium / chiral diene ligand and a monovalent gold as catalysts, the asymmetric 1,4-addition reaction of aryl rhodium species obtained through transmetalation with an aryl rhodium species to an azirmoniquinone intermediate generated in situ from an acetylamide substrate can yield an important class of chiral triarylmethane compounds in high yield and with enantioselectivity. Furthermore, by selecting chiral ligands with different configurations or changing the substituents on the acetylamide and arylboronic acid substrates, the method of this invention can yield various substituted chiral triarylmethane products with opposite configurations. Based on these findings, this invention was completed.

[0110] the term

[0111] As used herein, the terms "monovalent rhodium / chiral diene ligand" and "monovalent rhodium catalyst / chiral diene ligand" are used interchangeably, referring to complexes of a monovalent rhodium metal catalyst and a chiral diene ligand. A preferred class of monovalent rhodium / chiral diene ligands suitable for this invention are complexes formed by a monovalent rhodium metal catalyst and a compound of the following formula, which was first reported in CN201510082580.8:

[0112] or .

[0113] As used herein, the term "alkyl" refers to C1-C 10The alkyl group is a straight-chain, branched, or cyclic alkyl group. In this invention, the alkyl group further includes a group in which one or more H atoms on the alkyl group are replaced by substituents selected from the group consisting of: halogens, substituted or unsubstituted phenyl groups, unsubstituted or C-type alkyl groups substituted with one or more halogens. 1-6 Alkyl. It should be understood that the term also includes C. 3-10 Substituted or unsubstituted cycloalkyl groups.

[0114] As used herein, the term "alkoxy" refers to C1-C 10 The alkoxy group is a straight-chain, branched, or cyclic alkoxy group. In this invention, the alkoxy group also includes a group in which one or more H atoms on the alkyl group are replaced by substituents selected from the group consisting of: halogens, substituted or unsubstituted phenyl groups, unsubstituted or substituted C atoms with one or more halogens. 1-6 alkyl.

[0115] As used herein, the terms "aryl" or "Ar" refer to C6-C. 30 Aryl groups, representative examples of which are phenyl, naphthyl, anthraceneyl, and phenanthrene, are also included in this invention. In this invention, the aryl group further includes groups in which one or more H atoms on the aryl group are replaced by substituents selected from the group consisting of halogens, phenyl groups, unsubstituted or halogen-substituted C atoms. 1-6 Alkyl, unsubstituted, or C substituted with one or more halogens 1-6 Alkyl group.

[0116] As used in this article, the term "heteroaryl" refers to C6-C 30 A heteroaryl group has one or more heteroatoms, including but not limited to: N, O, S, P, etc. Representative examples are pyridyl, thiophene, indole, and furanyl. In this invention, the heteroaryl group also includes groups in which one or more H atoms on the heteroaryl group are replaced by substituents selected from the group consisting of: halogen, phenyl, nitro, unsubstituted or halogenated C atoms. 1-6 Alkyl, unsubstituted, or C substituted with one or more halogens 1-6 Alkyl group.

[0117] As used herein, the term "sulfonyl" refers to a group having a -SO2-R group, where R is a substituted or unsubstituted aryl group, which is as defined above, for example -SO2-C7H7, -SO2-C6H4NO2, or similar groups.

[0118] As used herein, the term "amino" refers to NH2, either alone or as part of other substituents.

[0119] As used herein, the term "nitro" refers to NO2, either alone or as part of other substituents.

[0120] As used herein, the term "carbonyl" means C=O, either alone or as part of other substituents.

[0121] As used herein, the term "metal coordination" refers to the complete or partial coordination of a transition metal atom or ion with the aryl group (as used herein) via coordinate bonds, thereby forming a compound or group with aromatic properties. The C of a metal coordination 6-20 Representative examples of aryl groups include, but are not limited to, ferrocene.

[0122] As used in this article, the term "halogen" refers to F, Cl, Br, or I.

[0123] As used herein, the term "one or more" generally refers to 1-6, preferably 1-5, and more preferably 1-3.

[0124] As used in this article, the term "Ph" refers to phenyl.

[0125] As used herein, the term "PMP" stands for p-methoxyphenyl.

[0126] As used in this article, the term “rt” refers to room temperature, such as 20–30°C.

[0127] Preparation method

[0128] The synthesis method of this invention can be represented by the following typical reaction formula:

[0129]

[0130] In the formula,

[0131] Ar 1 Selected from: substituted or unsubstituted C 6-30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl; wherein, the Ar 1 Substitution refers to having one or more substituents selected from the group consisting of halogens, C, and so on. 1-6 Alkyl, C 1-6 Haloalkyl, C 1-6 Alkoxy, C 6-14 Aryl, hydroxyl, or combinations thereof; the halogen is F, Cl, Br, or I;

[0132] Ar 2 Selected from: substituted or unsubstituted C 6-30 Aryl, substituted or unsubstituted 5-30 membered heteroaryl; wherein, the Ar 2 Substitution refers to having one or more substituents selected from the group consisting of halogens, C, and so on. 1-6 Alkyl, C 1-6 Alkoxy, C 6-10 Aryl, or combinations thereof; the halogen is F, Cl, Br, or I;

[0133] Ar 3Selected from: substituted or unsubstituted C 6-10 Aryl; wherein, the Ar 3 Substitution refers to having one or more substituents selected from the group consisting of: C 1-6 Alkoxy;

[0134] R 1 Selected from: substituted or unsubstituted C 1-6 alkylsulfonyl, substituted or unsubstituted benzenesulfonyl, wherein the R 1 Substitution refers to having one or more substituents selected from the group consisting of: C 1-6 Alkyl, C 1-6 Alkyl groups. [Rh(I)] refers to monovalent rhodium metal catalysts, representative examples of which include (but are not limited to): [Rh(C2H4)2Cl]2, [Rh(C2H4)2OH]2, [Rh(coe)2Cl]2, [Rh(coe)2OH]]2, [Rh(C2H4)2OMe]2, [Rh(coe)2OMe]2 or combinations thereof; [Au(I)] refers to monovalent gold metal catalysts, representative examples of which include (but are not limited to): PPh3AuCl, PPh3AuPF6, PPh3AuOTf, PPh3AuBF4, or combinations thereof.

[0135] In this invention, a representative chiral diene ligand has the following structural formula:

[0136] or

[0137] Among them, R 2 and R 3 Each of the substituents is independently substituted or unsubstituted phenyl, naphthyl, anthracene, or phenanthrene, and the substituent is selected from the group consisting of halogens, unsubstituted C groups, or C groups substituted with one or more halogens. 1-6 Alkyl or unsubstituted or C substituted with one or more halogens 1-6 Alkyl group.

[0138] In this invention, the R 2 and R 3 They may be the same or different; preferably, the R... 2 With R 3 For unreplaced Fiki.

[0139] In this invention, the structural formulas of typical compounds of chiral diene ligands include (but are not limited to):

[0140]

[0141] In this invention, the solvent is a conventional organic solvent, which can be C 1-4 Halogenated alkanes, C6-8 Aromatic hydrocarbons, oxaalkanes, or oxacycloalkanes; the C 1-4 The haloalkane is selected from the group consisting of: dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dichloropropane, 1-chlorobutane, or combinations thereof; the C... 6-8 The aromatic hydrocarbon is selected from the group consisting of toluene, chlorobenzene, xylene, or combinations thereof; the oxaalkane or oxacycloalkane is selected from the group consisting of diethyl ether, tetrahydrofuran, 1,4-dioxane, or combinations thereof.

[0142] In the above-described reaction method of the present invention, the reaction temperature is not particularly limited, and is generally from 0°C to 80°C, preferably from 20°C to 60°C, and more preferably from 30°C to 40°C.

[0143] In the above-described reaction method of the present invention, the reaction time is not particularly limited, and is usually 0.1-72 hours, preferably 1-48 hours.

[0144] In a preferred embodiment of the present invention, a representative synthesis method may be described as follows:

[0145] A monovalent gold catalyst and the reaction substrate acetylamidone 1 are dissolved in an organic solvent and reacted at room temperature for 0.5 hours. Then, the reaction substrate arylboronic acid 2, the monovalent rhodium catalyst, and the chiral diene ligand are added to the organic solvent. Finally, an aqueous solution of alkali is added, and the reaction is continued at 40°C for 2–48 hours to obtain the high optical purity chiral triarylmethane compound described in this invention. In this reaction, the molar ratio of reaction substrate 1, reaction substrate 2, rhodium(I) / chiral diene complex, gold(I) catalyst, and alkali is 1:3:0.05:0.03:1; the preferred reaction temperature is 40°C; and the preferred reaction solvent is a mixture of 1,2-dichloroethane and 1,4-dioxane.

[0146] High optical purity chiral triarylmethane compounds

[0147] The method of this invention can rapidly and efficiently prepare chiral triarylmethane compounds with high optical purity.

[0148] In this invention, taking the catalyst complex [Rh(S,S-4p)Cl]2 as an example, the asymmetric 1,4-addition reaction of acetylacetamides with different substituents and arylboronic acids can efficiently produce the desired reaction product with good yield and excellent enantioselectivity, up to 99%. The absolute configuration of the product is determined by single-crystal diffraction.

[0149] Synthetic applications

[0150] The present invention also provides applications of chiral triarylmethane compounds with high optical purity, particularly in the preparation of pharmaceutical intermediates or active compounds with high optical purity.

[0151] In a preferred embodiment of the present invention, a first representative application is as follows:

[0152]

[0153] In this application, the chiral triarylmethane compounds of the present invention are subjected to a substitution reaction to form an organotriarylmethane compound 4 containing a butenyl group, which can then be further converted into other useful products.

[0154] In another preferred embodiment of the invention, a second representative use is shown below:

[0155]

[0156] In this application, the chiral triarylmethane compound 4 of the present invention undergoes an intramolecular DA reaction to obtain a triarylmethane compound 5 containing an indoline group, which can then be further converted into other useful products.

[0157] In another preferred embodiment of the invention, a third representative use is shown below:

[0158]

[0159] In this application, the Ts-protected indoline compound 5 of the present invention is deprotected with Red-Al and then oxidized in air to obtain a deprotected triarylmethane compound 6 containing an indole group, which enriches the diversity of aromatic rings in the product.

[0160] In another preferred embodiment of the invention, a fourth representative use is shown below:

[0161]

[0162] In this application, the chiral triarylmethane compound 3-1 of the present invention is subjected to oxidative ring-opening with m-CPBA to obtain the important synthetic intermediate 1,4-dicarbonyl compound 7, which can be further converted into other useful products.

[0163] In another preferred embodiment of the invention, the fifth representative use is as follows:

[0164]

[0165] In this application, the chiral 1,4-dicarbonyl compound 7 of the present invention is subjected to a condensation-cyclization reaction in the presence of hydrazine hydrate to obtain a chiral triarylmethane compound 8 containing heteroarylpyridazine, which further enriches the diversity of aryl groups in the product.

[0166] In another preferred embodiment of the invention, the sixth representative use is as follows:

[0167]

[0168] In this application, the chiral compound 7 of the present invention is reduced by HSiCl3 to obtain compound 9.

[0169] In another preferred embodiment of the invention, the seventh representative use is as follows:

[0170]

[0171] In this application, the chiral compound 9 of the present invention is subjected to a condensation-cyclization reaction in the presence of hydrazine hydrate to obtain a chiral diarylmethane compound 10, thereby enriching the diversity of products.

[0172] In another preferred embodiment of the invention, the eighth representative use is as follows:

[0173]

[0174] In this application, the chiral triarylmethane compound 3 of the present invention is deprotected to obtain a chiral triarylmethane compound 11 with an imine.

[0175] Compared with the prior art, the main advantages of the present invention include:

[0176] (a) Using monovalent rhodium and monovalent gold as catalysts, and readily available acetylacetamide and arylboronic acid as reaction precursors, an asymmetric 1,4-addition reaction catalyzed by monovalent rhodium and monovalent gold was achieved under the action of chiral diene ligands. This can efficiently and selectively prepare chiral triarylmethane compounds that are extremely challenging to control enantioselectivity.

[0177] (b) The catalytic system has good reaction specificity, and no 1,2-addition byproducts were observed during the reaction.

[0178] (c) The method of the present invention requires a small amount of catalyst and has good substrate versatility;

[0179] (d) The method of the present invention has mild reaction conditions and is easy to operate;

[0180] (e) Through some simple methods and conditions, chiral triarylmethanes can be converted into various useful organic and pharmaceutical synthesis intermediates;

[0181] (f) The reaction of the present invention has good enantioselectivity and high optical purity of the product, and has promising applications in organic synthesis and drug development.

[0182] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions. Percentages and parts are by weight unless otherwise stated.

[0183] Example 1

[0184] Synthesis of compound 3-1

[0185] Experiment 1: The chiral diene ligand (S,S)-4p and [Rh(C2H4)2Cl]2 were dissolved in dry dichloromethane and stirred at room temperature for 1 hour to obtain the [Rh((S,S)-4p)Cl]2 complex. Trans-2-benzylmethylene-4-phenyl-N-p-toluenesulfonylbutyrylamide (0.1 mmol) was added to reaction flask A. After anhydrous and oxygen-free treatment, PPh3AuPF6 (0.006 M in DCE, 0.5 mL, 3.0 mol%) was added, and the mixture was stirred at 25 °C for 0.5 hours. p-Methylphenylboronic acid (0.3 mmol) and the previously prepared [Rh((S,S)-4p)Cl]2 complex (0.0025 mmol, 2.5 mol%) were added to another reaction flask B. After anhydrous and oxygen-free treatment, 1,4-dioxane (0.5 mL) was added, and then the solution from reaction flask A was added to reaction flask B. Cesium fluoride (1.0 M in H2O, 0.1 mL) was added, and the reaction was continued at 40 °C. After TLC monitoring showed that acetylamid compound 1 had completely reacted, the reaction solution was evaporated to dryness, and product 3-1 was obtained by silica gel column chromatography. It was a white solid with a yield of 87% and an ee of 98%.

[0186] Experiment 2: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4p, and follow the same experimental procedures as in Experiment 1. The product ent 3-1 was obtained as a white solid with a yield of 84% and an ee of 98%.

[0187] Experiment 3: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4a, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 91% and an ee of 77%.

[0188] Experiment 4: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4c, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 90% and an ee of 77%.

[0189] Experiment 5: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4i, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 89% and an ee of 77%.

[0190] Experiment 6: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4k, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 83% and an ee of 88%.

[0191] Experiment 7: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4n, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 85% and an ee of 90%.

[0192] Experiment 8: Replace the ligand (S,S)-4p used in Experiment 1 with (R,R)-4o, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 80% and an ee of 95%.

[0193] Experiments 9-12: Replace the cesium fluoride aqueous solution used in Experiment 1 with aqueous solutions of other bases (potassium hydroxide, potassium carbonate, potassium phosphate, potassium fluoride) in turn. The rest of the experimental procedures are the same as in Experiment 1. Product 3-1 is obtained, which is a white solid. Potassium hydroxide: 64% yield, 98% ee; potassium carbonate: 47% yield, 97% ee; potassium phosphate: 51% yield, 97% ee; potassium fluoride: 68% yield, 98% ee.

[0194] Experiments 13-14: Replace the 40℃ in Experiment 1 with other temperatures (25℃, 60℃) in turn, and follow the same experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid. 25℃: 62% yield, 98% ee; 60℃: 75% yield, 97% ee.

[0195] Experiment 15: Replace the amounts of monovalent rhodium and monovalent gold catalysts used in Experiment 1 with other amounts (rhodium: 1.5 mol%, gold: 5.0 mol%), and perform the remaining experimental procedures as in Experiment 1. The product 3-1 was obtained, which was a white solid with a yield of 45% and an ee of 98%.

[0196] Experiment 16: Replace 0.5 mL of 1,4-dioxane in Experiment 1 with 0.5 mL of 1,2-dichloroethane. Perform the remaining experimental procedures as in Experiment 1. Product 3-1 was obtained, which was a white solid with a yield of 63% and an ee of 98%.

[0197]

[0198] 1H NMR (400MHz, CDCl3) δ7.74(d,J=8.4Hz,2H),7.37(d,J=7.2Hz,2H),7.31–7.27(m,5H),7.24–7.20(m,3H),7.10–7.09(m, 4H),7.02(d,J=8.0Hz,2H),6.38(s,1H),6.26(s,1H),5.24(s,1H),2.42(s,3H),2.33(s,3H).ESI-MS(m / z,%)516[M+Na] + .

[0199] Based on the above experimental results, the conditions described in Experiment 1 were selected as the optimal experimental conditions for subsequent experiments.

[0200] Example 2

[0201] Synthesis of compound 3-2

[0202] The arylboronic acid 2-2 used in Example 1 was replaced with 2-3, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-2 was obtained as a white solid with a yield of 82% and an ee of 96%.

[0203]

[0204] 1 H NMR (600MHz, CDCl3) δ7.73(d,J=7.8Hz,2H),7.35(d,J=7.2Hz,2H),7.29–7.25(m,6H),7.21(t,J=7.2Hz,2H),7.12(d,J=7.8Hz,2H),7.0 4(d,J=8.4Hz,2H),6.81(d,J=8.4Hz,2H),6.36(s,1H),6.31(br,1H),5.23(s,1H),3.78(s,3H),2.41(s,3H).ESI-MS(m / z,%)532[M+Na] + .

[0205] Example 3

[0206] Synthesis of compound 3-3

[0207] The arylboronic acid 2-2 used in Example 1 was replaced with 2-4, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-3 was obtained, which was a white solid with a yield of 81% and an ee of 98%.

[0208]

[0209] 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.4Hz,2H),7.34(d,J=7.2Hz,2H),7.31–7.26(m,4H),7.25–7.22(m,6H),7.12(d,J =7.2Hz,2H),7.08(d,J=8.8Hz,2H),6.40(br,1H),6.35(s,1H),5.35(s,1H),2.40(s,3H).ESI-MS(m / z,%)536[M+Na] + .

[0210] Example 4

[0211] Synthesis of compounds 3-4

[0212] The arylboronic acid 2-2 used in Example 1 was replaced with 2-5, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-4 was obtained, which was a white solid with a yield of 84% and an ee of 98%.

[0213]

[0214] 1 H NMR (600MHz, CDCl3) δ7.72(d,J=8.4Hz,2H),7.34(d,J=7.2Hz,2H),7.30–7.27(m,4H),7.25–7.21(m,4H),7.14–7. 09(m,4H),6.96(t,J=8.4Hz,2H),6.39(br,1H),6.36(s,1H),5.35(s,1H),2.41(s,3H).ESI-MS(m / z,%)520[M+Na] + .

[0215] Example 5

[0216] Synthesis of compounds 3-5

[0217] The arylboronic acid 2-2 used in Example 1 was replaced with 2-6, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-5 was obtained, which was a white solid with a yield of 86% and an ee of 98%.

[0218]

[0219] 1H NMR (600MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.40(d,J=8.4Hz,2H),7.35(d,J=7.8Hz,2H),7.31–7.28(m,4H),7.25–7.22(m,4H),7 .13(d,J=7.8Hz,2H),7.03(d,J=7.8Hz,2H),6.51–6.45(m,1H),6.37(s,1H),5.34(s,1H),2.42(s,3H).ESI-MS(m / z,%)580[M+Na] + .

[0220] Example 6

[0221] Synthesis of compounds 3-6

[0222] The arylboronic acid 2-2 used in Example 1 was replaced with 2-7, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-6 was obtained, which was a white solid with a yield of 73% and an ee of 98%.

[0223]

[0224] 1 H NMR(400MHz, CDCl3)δ7.69(d,J=8.0Hz,2H),7.51(d,J=8.4Hz,2H),7.32–7.27(m,5H),7.24–7.18(m,7H) ,7.06(d,J=7.2Hz,2H),6.40(br,1H),6.34(s,1H),5.44(s,1H),2.38(s,3H).ESI-MS(m / z,%)570[M+Na] + .

[0225] Example 7

[0226] Synthesis of compounds 3-7

[0227] The arylboronic acid 2-2 used in Example 1 was replaced with 2-8, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-7 was obtained, which was a white solid with a yield of 93% and an ee of 95%.

[0228]

[0229] 1H NMR (400MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.36(d,J=7.6Hz,2H),7.29–7.27(m,5H),7.25–7.19(m,5H),7.13(d,J =7.6Hz,2H),7.03(d,J=8.4Hz,2H),6.39(s,1H),5.23(s,1H),2.41(s,3H),1.30(s,9H).ESI-MS(m / z,%)558[M+Na] + .

[0230] Example 8

[0231] Synthesis of compounds 3-8

[0232] The arylboronic acid 2-2 used in Example 1 was replaced with 2-9, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-8 was obtained, which was a white solid with a yield of 95% and an ee of 98%.

[0233]

[0234] 1 H NMR (400MHz, CDCl3) δ7.74(d,J=8.0Hz,2H),7.57(d,J=8.0Hz,2H),7.51(d,J=7.6Hz,2H),7.42(t,J=7.6Hz,2H),7. 38–7.28(m,7H),7.24–7.17(m,8H),6.42(s,1H),6.39(br,1H),5.36(s,1H),2.40(s,3H).ESI-MS(m / z,%)578[M+Na] + .

[0235] Example 9

[0236] Synthesis of compounds 3-9

[0237] The arylboronic acid 2-2 used in Example 1 was replaced with 2-10, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-9 was obtained, which was a white solid with a yield of 75% and an ee of 98%.

[0238]

[0239] 1H NMR (400MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.37(d,J=6.8Hz,2H),7.30–7.25(m,6H),7.32–7.15(m,3H),7.12(d,J=7.2 Hz,1H),6.93–6.90(m,2H),6.37(s,1H),6.26(br,1H),5.22(s,1H),2.41(s,3H),2.30(s,3H).ESI-MS(m / z,%)516[M+Na] + .

[0240] Example 10

[0241] Synthesis of Compounds 3-10

[0242] The arylboronic acid 2-2 used in Example 1 was replaced with 2-11, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-10 was obtained as a white solid with a yield of 93% and an ee of 99%.

[0243]

[0244] 1 H NMR (400MHz, CDCl3) δ7.74(d,J=8.0Hz,2H),7.38–7.36(m,2H),7.31–7.27(m,5H),7.25–7.21(m,4H),7.15(d,J=7.2Hz,2H),6.79 –6.76(m,1H),6.74(d,J=6.8Hz,2H),6.42(br,1H),6.40(s,1H),5.29(s,1H),3.76(s,3H),2.42(s,3H).ESI-MS(m / z,%)532[M+Na] + .

[0245] Example 11

[0246] Synthesis of compound 3-11

[0247] The arylboronic acid 2-2 used in Example 1 was replaced with 2-12, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-11 was obtained as a white solid with a yield of 90% and an ee of 98%.

[0248]

[0249] 1H NMR (400MHz, CDCl3) δ7.72(d,J=8.0Hz,2H),7.35(d,J=8.4Hz,2H),7.31–7.26(m,4H),7.25–7.19(m,6H),7.12(d,J=7.2Hz ,2H),7.07(s,1H),7.04(t,J=3.2Hz,1H),6.52(br,1H),6.36(s,1H),5.31(s,1H),2.40(s,3H).ESI-MS(m / z,%)536[M+Na] + .

[0250] Example 12

[0251] Synthesis of compound 3-12

[0252] The arylboronic acid 2-2 used in Example 1 was replaced with 2-13, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-12 was obtained as a white solid with a yield of 85% and an ee of 99%.

[0253]

[0254] 1 H NMR(400MHz, CDCl3)δ7.70(d,J=8.4Hz,2H),7.37(d,J=7.2Hz,2H),7.30–7.26(m,3H),7.25–7.19(m,5H),7.15–7.10(m,3H), 7.05(d,J=6.8Hz,2H),6.98(d,J=7.2Hz,1H),6.27(s,1H),5.43(s,1H),2.41(s,3H),2.16(s,3H).ESI-MS(m / z,%)516[M+Na] + .

[0255] Example 13

[0256] Synthesis of compound 3-13

[0257] The arylboronic acid 2-2 used in Example 1 was replaced with 2-14, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-13 was obtained as a white solid with a yield of 90% and an ee of 98%.

[0258]

[0259] 1H NMR (400MHz, CDCl3) δ7.70(d,J=8.4Hz,2H),7.46(d,J=7.2Hz,2H),7.31(t,J=7.6Hz,2H),7.25–7.20(m,5H),7.14(d,J=8.0Hz,2H),7.20(d, J=6.8Hz,2H),6.95(dd,J=7.6,1.2Hz,1H),6.88–6.85(m,2H),6.38(s,1H),5.41(s,1H),3.79(s,3H),2.33(s,3H).ESI-MS(m / z,%)532[M+Na] + .

[0260] Example 14

[0261] Synthesis of compound 3-14

[0262] The arylboronic acid 2-2 used in Example 1 was replaced with 2-17, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-14 was obtained as a white solid with a yield of 79% and an ee of >99%.

[0263]

[0264] 1 H NMR (400MHz, CDCl3) δ7.88(dd,J=18.0,8.0Hz,2H),7.77(d,J=8.4Hz,1H),7.70(d,J=8.4Hz,2H),7.48–7.36(m,5H),7 .30–7.22(m,6H),7.19–7.11(m,5H),6.28(br,1H),6.27(s,1H),5.99(s,1H),2.37(s,3H).ESI-MS(m / z,%)552[M+Na] + .

[0265] Example 15

[0266] Synthesis of compound 3-15

[0267] The arylboronic acid 2-2 used in Example 1 was replaced with 2-18, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-15 was obtained as a white solid with a yield of 99% and an ee of 98%.

[0268]

[0269] 1H NMR(600MHz, CDCl3)δ7.81(t,J=3.6Hz,1H),7.77–7.74(m,4H),7.53(s,1H),7.46–7.45(m,2H),7.39(d,J=7.8Hz,2H), 7.32–7.28(m,5H),7.25–7.18(m,6H),6.49(br,1H),6.44(s,1H),5.49(s,1H),2.36(s,3H).ESI-MS(m / z,%)552[M+Na] + .

[0270] Example 16

[0271] Synthesis of compound 3-16

[0272] The arylboronic acid 2-2 used in Example 1 was replaced with 2-19, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-16 was obtained as a white solid with a yield of 65% and an ee of 99%.

[0273]

[0274] 1 H NMR (400MHz, CDCl3) δ8.73(d,J=8.0Hz,1H),8.68(d,J=8.2Hz,1H),7.95(d,J=7.9Hz,1H),7.78–7.47(m,8H),7.41–7.36(m,3H),7.31– 7.26(m,4H),7.23–7.16(m,3H),7.11(d,J=8.0Hz,2H),6.34(s,1H),6.31(s,1H),5.98(s,1H),2.31(s,3H).ESI-MS(m / z,%)602[M+Na] + .

[0275] Example 17

[0276] Synthesis of compound 3-17

[0277] The arylboronic acid 2-2 used in Example 1 was replaced with 2-20, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. Product 3-17 was obtained, which was a white solid with a yield of 90% and an ee of 98%.

[0278]

[0279] 1H NMR (400MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.37(d,J=8.4Hz,2H),7.30–7.19(m,8H),7.10(d,J=8.0Hz,2H),6.85 (s,1H),6.71(s,2H),6.36(s,1H),6.27(br,1H),5.14(s,1H),2.41(s,3H),2.25(s,6H).ESI-MS(m / z,%)530[M+Na] + .

[0280] Example 18

[0281] Synthesis of compound 3-18

[0282] The arylboronic acid 2-2 used in Example 1 was replaced with 2-21, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-18 was obtained as a white solid with a yield of 87% and an ee of 95%.

[0283]

[0284] 1 H NMR(400MHz, CDCl3) δ7.73(d,J=8.0Hz,2H),7.35–7.33(m,2H),7.31–7.21(m,8H),7.15(d,J=7.2Hz,2H),6.78–6.76(m,2H),6.63 (dd,J=8.0,1.6Hz,1H),6.38(s,1H),6.35(br,1H),5.31(s,1H),3.85(s,3H),3.79(s,3H),2.42(s,3H).ESI-MS(m / z,%)562[M+Na] + .

[0285] Example 19

[0286] Synthesis of compound 3-19

[0287] The arylboronic acid 2-2 used in Example 1 was replaced with 2-22, and the amount was 0.3 mmol. The rest of the experimental procedures were the same as in Experiment 1 of Example 1. The product 3-19 was obtained as a white solid with a yield of 59% and an ee of 92%.

[0288]

[0289] 1H NMR (400MHz, CDCl3) δ7.72(d,J=8.0Hz,2H),7.36–7.34(m,2H),7.30–7.21(m,9H),7.18–7.16(m,2H),6.85(dd,J=5 .2,1.2Hz,1H),6.83–6.82(m,1H),6.41(s,1H),6.30(br,1H),5.30(s,1H),2.40(s,3H).ESI-MS(m / z,%)508[M+Na] + .

[0290] Example 20

[0291] Synthesis of compound 3-20

[0292] Replace acetylacetamide 1-1 used in Example 1 with 1-11, and use 0.1 mmol. Refer to Experiment 1 of Example 1 for the rest of the experimental procedures. The product 3-20 was obtained as a white solid with a yield of 68% and an ee of 98%.

[0293]

[0294] 1 H NMR (400MHz, CDCl3) δ7.72(d,J=8.0Hz,2H),7.37–7.35(m,2H),7.30–7.21(m,5H),7.17(dd,J=5.2,1.2Hz,1H),7.13–7.09(m,4H),6.91(d d,J=5.2,3.6Hz,1H),6.73(d,J=3.6Hz,1H),6.48(s,1H),6.33(br,1H),5.41(s,1H),2.40(s,3H),2.32(s,3H).ESI-MS(m / z,%)522[M+Na] + .

[0295] Example 21

[0296] Synthesis of Compound 3-21

[0297] Replace acetylacetamide 1-1 used in Example 1 with 1-3, and use 0.1 mmol. Refer to Experiment 1 of Example 1 for the rest of the experimental procedures. The product 3-21 was obtained as a white solid with a yield of 83% and an ee of 98%.

[0298]

[0299] 1H NMR (400MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.37–7.35(m,2H),7.30–7.20(m,5H),7.08(d,J=8.4Hz,2H),7.04–6.99(m,4H),6. 81(d,J=8.4Hz,2H),6.37(s,1H),6.33(br,1H),5.18(s,1H),3.38(s,3H),2.41(s,3H),2.32(s,3H).ESI-MS(m / z,%)546[M+Na] + .

[0300] Example 22

[0301] Synthesis of compound 3-22

[0302] Replace acetylacetamide 1-1 used in Example 1 with 1-4, and use 0.1 mmol. Refer to Experiment 1 of Example 1 for the rest of the experimental procedures. The product 3-22 was obtained as a white solid with a yield of 83% and an ee of 97%.

[0303]

[0304] 1 H NMR(400MHz, CDCl3)δ7.71(d,J=8.4Hz,2H),7.36–7.33(m,2H),7.30–7.22(m,7H),7.08(dd,J=12.0,8.0Hz,4H),7 .00(d,J=8.0Hz,2H),6.41(br,1H),6.35(s,1H),5.28(s,1H),2.41(s,3H),2.32(s,3H).ESI-MS(m / z,%)550[M+Na] + .

[0305] Example 23

[0306] Synthesis of compound 3-23

[0307] Replace acetylacetamide 1-1 used in Example 1 with 1-12, and use 0.1 mmol. Refer to Experiment 1 of Example 1 for the rest of the experimental procedures. The product 3-23 was obtained as a white solid with a yield of 77% and an ee of 99%.

[0308]

[0309] 1H NMR(400MHz, CDCl3)δ7.30(d,J=8.0Hz,2H),7.31–7.25(m,6H),7.22–7.19(m,1H),7.10(t,J=8.8Hz,4H),7.00(d,J=8.0Hz,2H), 6.82(d,J=9.2Hz,2H),6.23(s,1H),6.19(br,1H),5.20(s,1H),3.80(s,3H),2.42(s,3H),2.32(s,3H).ESI-MS(m / z,%)546[M+Na] + .

[0310] Example 24

[0311] Synthesis of compound 3-24

[0312] The acetylacetamide 1-1 used in Example 1 was replaced with 1-2, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-4, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. The product 3-24 was obtained as a white solid with a yield of 76% and an ee of 98%.

[0313]

[0314] 1 H NMR (600MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.35(d,J=7.8Hz,2H),7.29(t,J=7.2Hz,2H),7.26–7.22(m,5H),7.09(q,J=8.4 Hz,4H),7.02(d,J=8.4Hz,2H),6.43(br,1H),6.36(s,1H),5.30(s,1H),2.42(s,3H),2.33(s,3H).ESI-MS(m / z,%)550[M+Na] + .

[0315] Example 25

[0316] Synthesis of compound 3-25

[0317] The acetylacetamide 1-1 used in Example 1 was replaced with 1-6, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-3, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. Product 3-25 was obtained, which was a white solid with a yield of 84% and an ee of 97%.

[0318]

[0319] 1H NMR(400MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.35(d,J=7.2Hz,2H),7.30–7.26 (m,4H),7.21(q,J=7.2Hz,2H),7.05(d,J=8.8Hz,2H),6.82(d,J=8.8Hz,2H),6 .76(dd,J=8.4,2.4Hz,1H),6.71(d,J=8.4Hz,2H),6.37(s,1H),6.29(br,1H), 5.21(s,1H),3.79(s,3H),3.76(s,3H),2.42(s,3H).ESI-MS(m / z,%)562[M+Na] + .

[0320] Example 26

[0321] Synthesis of compound 3-26

[0322] The acetylacetamide 1-1 used in Example 1 was replaced with 1-6, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-4, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. The product 3-26 was obtained as a white solid with a yield of 84% and an ee of 98%.

[0323]

[0324] 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.4Hz,2H),7.35–7.32(m,2H),7.30–7.19(m,8H),7.08(d,J=8.4Hz,2H),6.77(dd,J=8.4,2 .0Hz,1H),6.72–6.69(m,2H),6.39(br,1H),6.35(s,1H),5.32(s,1H),3.76(s,3H),2.41(s,3H).ESI-MS(m / z,%)566[M+Na] + .

[0325] Example 27

[0326] Synthesis of compound 3-27

[0327] The acetylacetamide 1-1 used in Example 1 was replaced with 1-7, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-4, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. Product 3-27 was obtained, which was a white solid with a yield of 74% and an ee of 98%.

[0328]

[0329] 1 H NMR(400MHz, CDCl3)δ7.72(d,J=8.4Hz,2H),7.36–7.34(m,2H),7.32–7.22(m,9H),7.09–7.07(m,3H) ,7.06–7.03(m,1H),6.48(br,1H),6.34(s,1H),5.37(s,1H),2.42(s,3H).ESI-MS(m / z,%)570[M+Na] + .

[0330] Example 28

[0331] Synthesis of compound 3-28

[0332] Replace acetylacetamide 1-1 used in Example 1 with 1-5, and use 0.1 mmol. Refer to Experiment 1 of Example 1 for the rest of the experimental procedures. The product 3-28 was obtained as a white solid with a yield of 82% and an ee of 98%.

[0333]

[0334] 1 H NMR (400MHz, CDCl3) δ7.72(d,J=8.4Hz,2H),7.38–7.36(m,2H),7.29–7.24(m,4H),7.22–7.18(m,1H),7.15(t,J=7.6Hz,1H),7.07(d,J=8.0Hz,2H) ,7.02–6.98(m,3H),6.91–6.88(m,2H),6.36(s,1H),6.23(br,1H),5.15( s,1H),2.41(s,3H),2.31(s,3H),2.29(s,3H).ESI-MS(m / z,%)530[M+Na] + .

[0335] Example 29

[0336] Synthesis of compound 3-29

[0337] The acetylacetamide 1-1 used in Example 1 was replaced with 1-5, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-13, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. Product 3-29 was obtained, which was a white solid with a yield of 87% and an ee of 96%.

[0338]

[0339] 1H NMR (400MHz, CDCl3) δ7.71(d,J=8.4Hz,2H),7.38(d,J=7.2Hz,2H),7.30–7.21(m,5H),7.16–7.08(m,4H),7.02(d,J=7.6Hz,1H),6.97(d,J=7.2Hz, 1H),6.86(s,1H),6.82(d,J=7.6Hz,1H),6.26(s,1H),6.18(br,1H),5.35 (s,1H),2.41(s,3H),2.29(s,3H),2.16(s,3H).ESI-MS(m / z,%)530[M+Na] + .

[0340] Example 30

[0341] Synthesis of Compound 3-30

[0342] Replace acetylacetamide 1-1 used in Example 1 with 1-9, and use 0.1 mmol. Refer to Experiment 1 of Example 1 for the rest of the experimental procedures. The product 3-30 was obtained as a white solid with a yield of 84% and an ee of 94%.

[0343]

[0344] 1 H NMR (600MHz, CDCl3) δ7.71(d,J=8.4Hz,2H),7.38(d,J=7.8Hz,2H),7.30(t,J=7.2Hz,2H) ,7.25(d,J=8.4Hz,2H),7.20(t,J=7.2Hz,1H),7.15(d,J=3.6Hz,2H),7.11(q,J=4.2Hz,1 H),7.08(d,J=7.8Hz,2H),6.98(d,J=7.8Hz,1H),6.93(d,J=7.8Hz,2H),6.27(s,1H),6.1 6(br,1H),5.36(s,1H),2.42(s,3H),2.33(s,3H),2.16(s,3H).ESI-MS(m / z,%)530[M+Na] + .

[0345] Example 31

[0346] Synthesis of Compound 3-31

[0347] The acetylacetamide 1-1 used in Example 1 was replaced with 1-8, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-6, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. Product 3-31 was obtained, which was a white solid with a yield of 74% and an ee of 98%.

[0348]

[0349] 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.0Hz,2H),7.42(d,J=8.8Hz,2H),7.38–7.30(m,5H),7.28–7.24(m,4H),7.17(t,J=8.0Hz,1H ),7.08(d,J=7.6Hz,1H),7.02(d,J=8.4Hz,2H),6.46(s,1H),6.34(s,1H),5.34(s,1H),2.42(s,3H).ESI-MS(m / z,%)658[M+Na] + .

[0350] Example 32

[0351] Synthesis of Compound 3-32

[0352] The acetylacetamide 1-1 used in Example 1 was replaced with 1-10, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-18, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. The product 3-32 was obtained as a white solid with a yield of 82% and an ee of 96%.

[0353]

[0354] 1 H NMR (400MHz, CDCl3) δ7.95(d,J=8.4Hz,1H),7.86(d,J=8.0Hz,1H),7.81–7.74(m,3H),7.70–7.66(m,3H),7.46–7.34(m,8 H),7.30–7.24(m,3H),7.22–7.13(m,4H),6.35(s,1H),6.28(s,1H),6.13(s,1H),2.33(s,3H).ESI-MS(m / z,%)602[M+Na] + .

[0355] Example 33

[0356] Synthesis of compound 3-33

[0357] The acetylacetamide 1-1 used in Example 1 was replaced with 1-11, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-22, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. The product 3-33 was obtained as a white solid with a yield of 48% and an ee of 82%.

[0358]

[0359] 1 H NMR (600MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.36(d,J=7.2Hz,2H),7.31–7.27(m,4H),7.26–7.22(m,2H),7.19(dd,J=5.4,1.2Hz,1H),7.00–6. 98(m,2H),6.93(dd,J=5.4,3.6Hz,1H),6.82(d,J=3.6Hz,1H),6.52(s,1H),6.35(br,1H),5.58(s,1H),2.41(s,3H).ESI-MS(m / z,%)514[M+Na] + .

[0360] The above reaction produces triarylmethanes that are difficult to generate using conventional reaction methods and catalysts, indicating that the method of the present invention has very good substrate applicability.

[0361] Example 34

[0362] Synthesis of Compounds 3-34

[0363] The acetylacetamide 1-1 used in Example 1 was replaced with 1-11, and the amount was 0.1 mmol; the arylboronic acid 2-2 was replaced with 2-23, and the amount was 0.3 mmol. The remaining experimental procedures were the same as in Experiment 1 of Example 1. Product 3-34 was obtained, which was a white solid with a yield of 52% and an ee of 91%.

[0364]

[0365] 1H NMR(400MHz, CDCl3)δ7.71(d,J=8.4Hz,2H),7.39–7.37(m,3H),7.31–7.28(m ,2H),7.26–7.21(m,3H),7.19(dd,J=5.2,1.2Hz,1H),6.93(dd,J=5.2,3.6Hz ,1H),6.84(d,J=3.6Hz,1H),6.64(s,1H),6.42(s,1H),6.32(q,J=1.6Hz,1H) ,6.14(d,J=3.6Hz,1H),5.53(s,1H),2.40(s,3H).ESI-MS(m / z,%)498[M+Na] + .

[0366] The above reaction produces triarylmethanes that are difficult to generate using conventional reaction methods and catalysts, indicating that the method of the present invention has very good substrate applicability.

[0367] Example 35

[0368] Synthesis of Compound 4

[0369] Compound 3-1 (0.1 mmol, 49.3 mg, 98% ee) and potassium carbonate were added to a reaction flask, followed by acetone (1.0 mL), and then 4-bromo-1-butene (0.2 mmol, 20.3 μL, 2.0 eq). The system was heated to 60 °C and reacted for 2 hours. After the reaction was complete as monitored by TLC, it was cooled to room temperature and quenched by adding saturated ammonium chloride solution. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 4, a yellow solid, in 89% yield (98% ee).

[0370]

[0371] 1H NMR (600MHz, CDCl3) δ7.72(d,J=8.4Hz,2H),7.37(d,J=10.8Hz,2H),7.29(dd,J=12.6,7. 8Hz,6H),7.26–7.20(m,4H),7.12(dd,J=22.8,8.4Hz,4H),6.49(s,1H),5.55(s,1H),5.50 –5.43(m,1H),4.84(dd,J=10.8,1.8Hz,1H),4.76(dd,J=16.8,1.8Hz,1H),3.42(dd,J=7. 8,5.4Hz,2H),2.44(s,3H),2.32(s,3H),1.91(q,J=7.2Hz,2H).ESI-MS(m / z,%)570[M+Na] + .

[0372] Example 36

[0373] Synthesis of Compound 5

[0374] Compound 4 (0.1 mmol, 54.7 mg, 98% ee) was added to a reaction flask, followed by the addition of dry toluene (1.0 mL). The system was then heated to 140 °C and refluxed for 10 hours. After the reaction was completed by TLC monitoring, it was cooled to room temperature and quenched by the addition of saturated sodium chloride solution. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 5, a pale yellow solid, in 69% yield (97% ee).

[0375]

[0376] 1 H NMR (600MHz, CDCl3) δ7.46(d,J=7.8Hz,2H),7.43(d,J=7.2Hz,2H),7.37(t,J=7.2Hz,2H),7.31–7.16(m,10H),7.10(q,J=8 .4Hz,4H),6.82(s,1H),3.88(t,J=7.2Hz,2H),2.39(s,3H),2.32(s,3H),2.20(t,J=7.2Hz,2H).ESI-MS(m / z,%)552[M+Na] + .

[0377] Example 37

[0378] Synthesis of Compound 6

[0379] Compound 5 (0.1 mmol, 52.9 mg, 97% ee) was added to a reaction flask, followed by 1.0 mL of dried toluene. Then, Red-Al (0.4 mmol, 115.2 mg, 4.0 eq) was added to the system. The system was then heated to 120 °C and refluxed for 4 hours. After the reaction was completed by TLC monitoring, it was cooled to room temperature and quenched by adding saturated ammonium chloride solution. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 6, a pale yellow oil, in 73% yield (93% ee).

[0380]

[0381] 1 H NMR (600MHz, CDCl3) δ7.77(s,1H),7.65(s,1H),7.53(dd,J=8.2,1.0Hz,2H),7.38(t,J=7.7Hz,2H),7.31(t,J=7.4Hz,2H),7.28–7.26(m,1H), 7.26–7.21(m,3H),7.13–7.10(m,4H),7.07–7.04(m,1H),7.02(s,1H), 6.58–6.54(m,1H),5.79(s,1H),2.34(s,3H).ESI-MS(m / z,%)396[M+Na] + .

[0382] Example 38

[0383] Synthesis of Compound 7

[0384] Compound 3-1 (0.1 mmol, 49.3 mg, 98% ee) was added to a reaction flask, followed by 1.0 mL of dry dichloromethane. Then, m-CPBA (0.17 mmol, 29.4 mg, 1.7 eq) was added to the system. The reaction was carried out at 25 °C for 2 hours. After the reaction was completed by TLC monitoring, saturated sodium thiosulfate solution was added dropwise to quench the reaction. The mixture was then extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 7, an orange-yellow solid, in 74% yield, 98% ee.

[0385]

[0386] 1H NMR (600MHz, CDCl3) δ7.73(d,J=8.4Hz,2H),7.36(d,J=8.4Hz,2H),7.29–7.25(m,6H),7.21(td,J=7.2,1.2Hz,2H),7.10(dd,J=18. 0,8.4Hz,4H),7.01(d,J=8.4Hz,2H),6.37(s,1H),6.28(br,1H),5.24(s,1H),2.41(s,3H),2.32(s,3H).ESI-MS(m / z,%)532[M+Na] + .

[0387] Example 39

[0388] Synthesis of Compound 8

[0389] Compound 7 (0.1 mmol, 50.9 mg, 98% ee) was added to a reaction flask, DMF (1.0 mL) was added, and then hydrazine hydrate (0.2 mmol, 6.1 μL, 2.0 eq) was added to the system. The reaction was carried out at 40 °C for 2 hours. After the reaction was completed by TLC monitoring, it was cooled to room temperature and quenched by adding saturated ammonium chloride solution. Then it was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 8, a white solid, 67% yield, 92% ee.

[0390]

[0391] 1 H NMR(400MHz, CDCl3)δ11.08(br,1H),7.64–7.61(m,2H),7.42–7.40(m,3H),7.33(t,J=8.0Hz,2H),7.28–7 .26(m,2H),7.18–7.13(m,4H),7.05(d,J=8.0Hz,2H),5.82(s,1H),2.34(s,3H).ESI-MS(m / z,%)375[M+Na] + .

[0392] Example 40

[0393] Synthesis of Compound 9

[0394] Compound 7 (0.1 mmol, 50.9 mg, 98% ee) and triphenylphosphine oxide (0.5 mmol, 139 mg, 5.0 eq) were added to a reaction flask. After anhydrous and oxygen-free treatment, DCE (1.0 mL) was added, followed by trichlorosilane (1.0 mmol, 100 μL, 10.0 eq). The reaction was carried out at 25 °C for 0.5 h. After the reaction was complete as monitored by TLC, saturated ammonium chloride solution was added dropwise to quench the reaction. The mixture was then extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 9, a white solid, 67% yield, 1:1 dr, 98% ee.

[0395]

[0396] 1 H NMR(400MHz, CDCl3)δ8.69(br,1H),7.76–7.72(m,2H),7.61(q,J=4.0Hz,2H),7.53(td ,J=7.2,1.2Hz,1H),7.38(t,J=7.2Hz,2H),7.26–7.24(m,2H),7.21–7.05(m,8H),6.93 (d,J=8.0Hz,1H),4.09(d,J=12.0Hz,1H),3.83–3.76(m,1H),3.45–3.37(m,1H),3.02– 2.94(m,1H),2.35(d,J=6.4Hz,3H),2.26(d,J=13.2Hz,3H).ESI-MS(m / z,%)534[M+Na] + .

[0397] Example 41

[0398] Synthesis of Compound 10

[0399] Compound 9 (0.1 mmol, 51.1 mg, 1:1 dr, 98%, 98% ee) was added to a reaction flask, followed by EtOH (0.5 mL) and DCM (0.5 mL). Then, hydrazine hydrate (0.2 mmol, 6.1 μL, 2.0 eq) was added to the system. The reaction was carried out at 40 °C for 2 hours. After the reaction was completed by TLC monitoring, it was cooled to room temperature and quenched dropwise with saturated ammonium chloride solution. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to give product 10, a white solid, 66% yield, 1.5:1 dr, 97% ee.

[0400]

[0401] 1H NMR(600MHz, CDCl3)δ8.49(s,1H),7.56–7.46(m,2H),7.41–7.26(m,5H),7.25(s,1H),7.20(m,3H),7.18–7.02 (m,3H),4.35(dd,J=25.8,9.2Hz,1H),3.45(m,1H),2.95–2.80(m,2H),2.30(s,3H).ESI-MS(m / z,%)377[M+Na] + .

[0402] Example 42

[0403] Synthesis of Compound 11

[0404] Compound 3-1 (0.1 mmol, 49.3 mg, 98% ee) and potassium carbonate (0.2 mmol, 27.6 mg, 2.0 eq) were added to a reaction flask, followed by DMF (1.0 mL). Methyl bromoacetate (0.15 mmol, 14.2 μL, 1.5 eq) was then added to the system. The reaction was carried out at 80 °C for 8 hours. After the reaction was completed by TLC monitoring, saturated ammonium chloride solution was added dropwise to quench the reaction. The mixture was then extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, and the organic phase was removed by rotary evaporation. The residue was separated by silica gel column chromatography to obtain product 11, a pale yellow solid, in 46% yield (97% ee).

[0405]

[0406] 1 H NMR (400MHz, CDCl3) δ7.97 (s, 1H), 7.67 (d, J = 7.2Hz, 2H), 7.38 (t, J = 8.0Hz, 2H), 7.34–7.28 (m, 3H), 7.24–7. 20(m,3H),7.14–7.09(m,4H),6.68(s,1H),5.89(s,1H),3.91(s,3H),2.32(s,3H).ESI-MS(m / z,%)432[M+Na] + .

[0407] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A process for the preparation of a triarylmethane compound of high optical purity, characterized in that, The method comprises the following steps: In the presence of monovalent rhodium / chiral bisolefin ligand and monovalent gold catalyst, the acetylenic amide compound shown in formula 1 generates in-situ azo-ortho-methylene heteroaryl quinone intermediate, and the asymmetric 1,4-addition reaction with aryl boronic acid shown in formula 2, thereby obtaining the chiral triarylmethane compound shown in formula 3 or formula ent-3; In the formula, Ar 1 is selected from the group consisting of substituted or unsubstituted C 6-30 aryl, substituted or unsubstituted 5-30 membered heteroaryl; wherein the substitution of said Ar 1 means that one or more H on the group is replaced with a group selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 6-14 aryl, hydroxyl; and said halogen is F, Cl, Br, or I; Ar 2 is selected from the group consisting of substituted or unsubstituted C 6-30 aryl, substituted or unsubstituted 5-30 membered heteroaryl; wherein the Ar 2 substitution means that one or more H's on the group are replaced with a group selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 alkoxy, C 6-10 aryl; and the halogen is F, Cl, Br, or I; Ar 3 selected from the group consisting of substituted or unsubstituted C 6-10 aryl; wherein the Ar 3 substituted means that one or more H on the group is replaced with a member selected from the group consisting of C 1-6 alkoxy; R 1 selected from: substituted or unsubstituted C 1-6 alkylsulfonyl, substituted or unsubstituted phenylsulfonyl, wherein the R 1 substitution means having one or more substituents selected from the group consisting of C 1-6 alkyl, C 1-6 alkoxy; The monovalent rhodium and chiral bisolefin ligand form a complex before being added to the reaction system, or are added to the reaction liquid separately and form a complex in-situ.

2. The method of claim 1, wherein: Ar 1 selected from the group consisting of: substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted phenanthryl, substituted or unsubstituted thienyl, substituted or unsubstituted furanyl; said substitution is one or more H on the group is replaced with a group selected from the group consisting of: halo, C 1-4 alkyl, C 1-4 haloalkyl, C 1-4 alkoxy, C 6-14 aryl, hydroxyl, or a combination thereof; said halo is F, Cl, Br, or I; Ar 2 is selected from the group consisting of: substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5-7 membered heteroaryl; wherein said substitution is one or more H on the group is replaced with a group selected from the group consisting of: halogen, C 1-4 alkyl, C 1-4 alkoxy, C 6-10 aryl, or combinations thereof; and said halogen is F, Cl, Br, or I. Ar 3 is selected from the group consisting of: substituted or unsubstituted phenyl; wherein said substitution is one or more H on the group is substituted with a group selected from the group consisting of: C 1-4 alkoxy.

3. The method of claim 1, wherein, The chiral bisolefin ligand has the following structural formula: In the formula, R 2 , R 3 each independently is a substituted or unsubstituted C 6-30 aryl group, a substituted or unsubstituted metal-complexed C 6-30 aryl group, wherein R 2 and R 3 may be the same or different; said substitution means that one or more H is replaced by a group selected from the group consisting of halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, nitro, -CON i Pr2.

4. The method of claim 1, wherein, The monovalent rhodium catalyst is selected from the group consisting of [Rh(C2H4)2Cl]2, [Rh(C2H4)2OH]2, [Rh(coe)2Cl]2, [Rh(coe)2OH]]2, [Rh(C2H4)2OMe]2, [Rh(coe)2OMe]2, or a combination thereof; and the monovalent gold catalyst is selected from the group consisting of PPh3AuCl, PPh3AuPF6, PPh3AuOTf, PPh3AuBF4, or a combination thereof.

5. The method of claim 1, wherein, The method further comprises one or more features selected from the group consisting of: (1) the amount of monovalent rhodium catalyst is 0.1-20 mol% based on the amount of compound of formula 1; (2) the amount of chiral bisolefin ligand is 0.12-22 mol% based on the amount of compound of formula 1; (3) the amount of monovalent gold catalyst is 1.0-10 mol% based on the amount of compound of formula 1; (4) the organic solvent is C 1-4 haloalkane, C 6-8 aromatic hydrocarbon, oxoalkane, or oxacycloalkane, or a combination thereof; the C 1-4 haloalkane is selected from the group consisting of dichloromethane, 1,2-dichloroethane, chloroform, 1,2-dichloropropane, 1-chlorobutane, or a combination thereof; the C 6-8 aromatic hydrocarbon is selected from the group consisting of toluene, chlorobenzene, xylene, or a combination thereof; the oxoalkane or oxacycloalkane is selected from the group consisting of diethyl ether, tetrahydrofuran, 1,4-dioxane, or a combination thereof; (5) the addition reaction temperature is 0-80℃; (6) the addition reaction time is 0.1-72 hours.

6. A compound of formula 3 or formula ent-3, In the formula, Ar 1 , Ar 2 , Ar 3 , R 1 as defined in claim 1; preferably, R 1 is aryl substituted sulfonyl; more preferably, R 1 is p-toluenesulfonyl; most preferably, the compound is selected from the group consisting of:

7. Use of a compound as claimed in claim 6, characterized in that for preparing a chiral synthetic building block, a pharmaceutical intermediate or an active compound shown in the following formula: wherein Ar 1 , Ar 2 , Ar 3 , R 1 as defined in claim 1.

8. A method of preparing a compound of the following formula 4-1: ###00019### 4-1 comprising the steps of: ​ substituting the structure shown in formula 3-1 with 4-bromo-1-butene to form a chiral triarylmethane compound 4-1; wherein Ar 1 , Ar 2 , Ar 1 , R 1 are as defined in claim 1.

9. A method of preparing a compound of the following formula 5-1: ###00013### 5-1 characterized in that, The method comprises the steps of: (1) preparing the compound of formula 4-1 by the method of claim 8; and (2) subjecting the compound 4-1 to intramolecular D-A reaction to obtain compound 5-1.

10. A method of preparing a compound of the following formula 6-1: ###00014### 6-1 characterized in that, The method comprises the steps of: (1) preparing the compound of formula 5-1 by the method of claim 9; and (2) subjecting the compound 5-1 to deprotection and then oxidation to obtain compound 6-1.

11. A method of preparing a compound of the following formula 7-1: ###00015### 7-1 characterized in that, The method comprises the steps of: subjecting compound 3-1 to oxidative ring-opening to obtain compound 7-1.

12. A method for preparing a compound represented by formula 8-1, characterized in that, The method comprises the steps of: (1) preparing the compound of formula 7-1 by the method of claim 11; and (2) subjecting the compound 7-1 to condensation-cyclization reaction to obtain compound 8-1.

13. A method for preparing a compound represented by formula 9-1, characterized in that, The method comprises the steps of: (1) preparing the compound of formula 7-1 by the method of claim 11; and (2) subjecting the compound 7-1 to reduction reaction to obtain compound 9-1.

14. A method for preparing a compound represented by formula 10-1, characterized in that, The method comprises the steps of: (1) preparing a compound of formula 9-1 using the method of claim 13; and (2) subjecting said compound of 9-1 to a condensation-cyclization reaction to obtain compound 10-1.

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