Axially chiral bipyridine ligands, methods for their preparation and use

Abstract

This invention discloses an axially chiral bipyridine ligand, its preparation method, and its uses. The axially chiral bipyridine ligand has the structure of general formula (Ⅰ): the axially chiral bipyridine ligand contains a binaphthalene structure, wherein part A is selected from A-1, A-2, or A-3; part B is a hydrogen atom or is the same as part A. The complex catalyst formed in situ in the reaction system of the axially chiral bipyridine ligand and copper salt in this invention exhibits high catalytic activity, good to excellent enantioselectivity, and good substrate universality in the asymmetric ring-opening iodination, thioesterification, and hydrolysis of cyclic diaryliodonium salts to synthesize highly optically pure, diverse substituted 1,1'-bi-2-iodobenzene compounds, 1,1'-bi-2'-iodo-2-thioester compounds, and 1,1'-bi-2'-iodo-2-phenol compounds, respectively, showing great promise for industrial applications. This invention belongs to the field of asymmetric synthetic chemistry.

Description

Technical Field

[0001] This invention belongs to the field of asymmetric synthetic chemistry, specifically relating to a novel class of axially chiral bipyridine ligands, their preparation methods, and applications. Catalysts formed by these ligands and copper salts can be used for asymmetric ring-opening iodination, thioesterification, and hydrolysis reactions of various cyclic aryl iodonium salts, respectively synthesizing highly optically pure, diverse substituted 1,1'-bi-2-iodobenzene compounds, 1,1'-bi-2'-iodo-2-thioester compounds, and 1,1'-bi-2'-iodo-2-phenol compounds. These compounds exhibit high catalytic activity and enantioselectivity, showing promising applications in the synthesis of related chiral molecules. Background Technology

[0002] Axially chiral biaryl structures are not only widely found in natural products and drug molecules, but also form the core framework of many chiral ligands and catalysts, playing a crucial role in asymmetric synthesis. 1,1'-bi-2-naphthol (BINOL), as one of the most representative axially chiral molecules, is widely used in materials chemistry and asymmetric synthetic chemistry. Developing novel and efficient chiral ligands / catalysts is a core research focus in asymmetric catalysis. Bipyridine is an important achiral, nitrogen-containing bidentate ligand with significant applications in transition metal catalysis. In 1984, Botteghi et al. reported the first chiral bipyridine ligand (C. Botteghi, et al. J. Org. Chem. 1984, 49, 4290-4293). In 2015, Zhou Yonggui's research group reported a palladium-catalyzed enantioselective C–H functionalization reaction of indole using an axially chiral 2,2'-bipyridine as a ligand, obtaining a series of indole-3-acetic acid derivatives with an enantioselectivity of up to 98% (YGZhou, et al. Angew. Chem., Int. Ed. 2015, 54, 11956-11960). Li Pengfei's research group developed chiral pyridine structural units containing a [6-5-3] rigid fused ring structure, designed and synthesized a class of chiral bipyridine ligands with a new skeleton, and investigated the reactivity and catalytic effect of the ligands with metals in asymmetric addition reactions, asymmetric Ullmann reactions and asymmetric carboxylation reactions (P.Li, et al. Angew. Chem., Int. Ed. 2022, 61, e202117843; P.Li, et al. Angew. Chem., Int. Ed. 2022, 61, e202212108; P.Li, et al. Angew. Chem., Int. Ed. 2022, 61, e202213943). In 2024, Gu Zhenhua's research group reported a class of bipyridine ligands with an axially chiral skeleton and successfully applied them to the copper-catalyzed ring-opening reaction of cyclic diaryl iodonium salts with sterically hindered secondary amines, achieving high conversion efficiency and stereoselectivity (Z.Gu, et al. Angew. Chem., Int. Ed. 2024, e202416839). While chiral bipyridine ligands have undergone decades of development, most remain centrally chiral, and the types of asymmetric catalytic reactions applicable to the reported bipyridine ligands are limited. Transition metal-catalyzed asymmetric ring-opening reactions of cyclic diaryl compounds are one of the most efficient methods for constructing axially chiral biaryl compounds. The asymmetric ring-opening reaction of cyclic diaryl iodonium salts can be used to synthesize various axially chiral biaryl compounds containing carbon-iodine bonds. These products can serve as synthetic intermediates for many axially chiral compounds and have significant application prospects. Currently, the chiral ligands suitable for this type of reaction are mainly chiral bisoxazoline and pyridineoxazoline ligands, resulting in a relatively simple catalytic system.The development of novel chiral ligands and catalysts for the synthesis of diverse substituted 1,1'-bi-2-iodobenzene compounds, 1,1'-bi-2'-iodo-2-thioester compounds, and 1,1'-bi-2'-iodo-2-phenol compounds has high practical application value. Summary of the Invention

[0003] The purpose of this invention is to provide a novel class of axially chiral bipyridine ligands (I).

[0004] Another objective of this invention is to provide a method for synthesizing the above-mentioned chiral ligands.

[0005] Another object of the present invention is to provide the use of the above-mentioned chiral ligands, namely, to form catalysts with copper salts for the asymmetric synthesis of 1,1'-bi-2-iodobenzene compounds, 1,1'-bi-2'-iodo-2-thioester compounds and 1,1'-bi-2'-iodo-2-phenol compounds with diverse substitutions.

[0006] This invention provides an axially chiral bipyridine ligand, characterized in that the axially chiral ligand is represented by the following general formula (Ⅰ):

[0007]

[0008] In the above formula (Ⅰ):

[0009] The naphthalene moiety A of the axially chiral bipyridine ligand is A-1, A-2, or A-3; the B moiety of the axially chiral bipyridine ligand is a hydrogen atom or the same as A.

[0010] The axial chirality marked with * indicates either R-configuration or S-configuration;

[0011] R 1 C 1-6 Any one of alkyl, alkoxy, hydroxy, phenyl, and substituted aryl groups;

[0012] R 2 C 1-6 Any one of alkyl, alkoxy, phenyl, or substituted aryl groups;

[0013] R 3 C 1-6 Any one of alkyl, alkoxy, alkylamine, phenyl, or substituted aryl.

[0014] In a preferred experimental scheme of the present invention, when R 1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when the R 1When the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or hexoxy; when the R 1 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

[0015] In a preferred experimental scheme of the present invention, when R 2 C 1-6 When alkyl is used, the alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when R 2 When the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or hexoxy; when the R 2 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

[0016] In a preferred experimental scheme of the present invention, when R 3 C 1-6 When alkyl is used, the alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when R 3 When the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or hexoxy; when the R 3 When the alkylamine group is alkylamine, the alkylamine group is dimethylamino, diethylamino, dipropylamino, diisopropylamino, di-n-butylamino, diisobutylamino, di-sec-butylamino, di-tert-butylamino, di-n-pentylamino, diisopentylamino, dineopentylamino, or dihexylamino; when the R 3 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

[0017] The present invention also provides a method for preparing the axially chiral bipyridine ligand, characterized by the following steps:

[0018] (1) Compound 3 is prepared by reacting compound 1 and compound 2 in an organic solvent under nitrogen or inert gas in the presence of palladium salt, ligand and base.

[0019]

[0020] (2) Compound 6 is prepared by reacting compound 4 and compound 5 in an organic solvent under nitrogen or inert gas with a condensing agent.

[0021]

[0022] (3) Compound 7 and compound 5 are reacted in an organic solvent under nitrogen or inert gas to prepare compound 8.

[0023]

[0024] Y of compound 2 1 It is a chlorine atom, a bromine atom, or an iodine atom; Y 2 With Y 1 The structures are the same or are hydrogen; in compound 3, B is hydrogen or equal to A-1; in compound 5, Y... 3 It can be hydrogen or carboxyl; in compound 6, B is hydrogen or equal to A-2; in compound 8, B is hydrogen or equal to A-3.

[0025] In this invention, the organic solvent is a solvent commonly used in the field of organic synthesis, and the organic solvent is one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, trichloromethane, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide;

[0026] In this invention, the inert gas includes one or more of argon, helium, neon, and krypton;

[0027] In this invention, the base is a base commonly used in the field of organic synthesis, including one or more of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, pyridine, and 4-dimethylaminopyridine;

[0028] In this invention, the palladium catalyst is a catalyst commonly used in the field of organic synthesis, including one or more of tetratetraphenylphosphine palladium, bis(triphenylphosphine)dichloride palladium, tri-(dibenzylacetone)palladium, and palladium acetate;

[0029] In this invention, the ligands are ligands commonly used in the field of organic synthesis, including one or more of triphenylphosphine, 1,1'-bis(diphenylphosphine)ferrocene, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, and 1,1'-binaphthyl-2,2'-bisdiphenylphosphine.

[0030] In this invention, the condensing reagent is a condensing reagent commonly used in the field of organic synthesis, including one or more of N,N'-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, and N,N'-carbonyldiimidazole;

[0031] In this invention, the reaction temperature can be the conventional reaction temperature for this type of reaction in the field of organic synthesis, such as 70°C.

[0032] In this invention, the reaction time can be the conventional reaction time for this type of reaction in the field of organic synthesis, and the reaction time is 1-60h, for example 24h.

[0033] In this invention, the molar concentration of the reactive compound in the organic solvent is 0.01-2 mol / L, for example, 0.5 mol / L.

[0034] In this invention, the synthesis reaction is further performed under reduced pressure for solvent removal after completion.

[0035] In this invention, the synthesis reaction is followed by a quenching process. The quenching solution can be a conventional quenching solution for this type of reaction in the field of organic synthesis, such as a saturated ammonium chloride solution or a sodium hydroxide solution.

[0036] In this invention, after the synthesis reaction is completed, a post-processing step is also included. The post-processing step can be a conventional post-processing step in the art, including one or more steps such as extraction, washing, drying, and column chromatography.

[0037] In this invention, the extractant can be a conventional extractant in the field of organic synthesis, including ethyl acetate, dichloromethane, chloroform, and diethyl ether. The washing solution can be a conventional washing solution in the field, such as a saturated sodium chloride solution; the drying can be done using a conventional desiccant in the field, such as anhydrous sodium sulfate or anhydrous magnesium sulfate; the column chromatography can be conventional silica gel column chromatography in the field of organic synthesis, and the eluent used in the column chromatography can be a conventional eluent in the field of organic synthesis, such as one or a mixture of several of petroleum ether, dichloromethane, ethyl acetate, or methanol.

[0038] The present invention also provides a method for synthesizing chiral, diversified substituted 1,1'-bi-2-iodobenzene compounds, comprising the following steps: in an inert environment, the above-mentioned axially chiral bipyridine ligand is complexed with a copper salt in an organic solvent to form a catalyst in situ, and then compound 9 and an iodine source are reacted at a desired reaction temperature according to the following formula, and after a desired reaction time, compound 10 is obtained;

[0039]

[0040] Among them, R 4 -R 11 It can be hydrogen, alkyl, phenyl, substituted phenyl, carboxyl, ester, halogen, or naphthyl;

[0041] The chiral axis marked with * is either S-configuration or R-configuration.

[0042] This invention also provides a method for synthesizing chiral, diversified substituted 1,1'-bi-2'-iodo-2-thioester compounds, comprising the following steps: under an inert environment, complexing the above-mentioned axially chiral bipyridine ligand with a copper salt in an organic solvent to form a catalyst in situ, followed by the addition of compound 9 and sulfur source R. 12 SK undergoes the reaction as follows at the desired reaction temperature and after the desired reaction time to obtain compound 11;

[0043]

[0044] Among them, R 4 -R 11 It can be hydrogen, alkyl, phenyl, substituted phenyl, carboxyl, ester, halogen, p-toluenesulfonyloxy, or naphthyl;

[0045] R 12 It is an alkyl acyl, phenyl acyl, substituted phenyl acyl, 2-naphthyl acyl, furanyl, thiophene acyl, benzenesulfonyl, or alkylflavinyl;

[0046] The chiral axis marked with * is either S-configuration or R-configuration.

[0047] The present invention also provides a method for synthesizing chiral, diversified substituted 1,1'-bi-2'-iodo-2-phenol compounds, comprising the following steps: in an inert environment, the above-mentioned axially chiral bipyridine ligand is complexed with a copper salt in an organic solvent to form a catalyst in situ, and then compound 9 and water are reacted at a desired reaction temperature and after a desired reaction time to obtain compound 12;

[0048]

[0049] Among them, R 4 -R 11 It can be hydrogen, alkyl, phenyl, substituted phenyl, carboxyl, ester, halogen, or naphthyl;

[0050] The chiral axis marked with * is either S-configuration or R-configuration.

[0051] In this invention, when R 4 -R 11 When the alkyl group is alkyl, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl.

[0052] In this invention, when the R 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group.

[0053] In this invention, when R 12 When R is an alkyl acyl group, the alkyl acyl group is methyl acyl, ethyl acyl, isopropyl acyl, n-butyl acyl, isobutyl acyl, tert-butyl acyl, cyclopentyl acyl, or cyclohexyl acyl; 12 When the phenyl acyl group is substituted, the substituted phenyl acyl group is a methyl-substituted phenyl acyl group, an ethyl-substituted phenyl acyl group, an isopropyl-substituted phenyl acyl group, a tert-butyl-substituted phenyl acyl group, a trifluoromethyl-substituted phenyl acyl group, a methoxy-substituted phenyl acyl group, an ethoxy-substituted phenyl acyl group, a tert-butyloxy-substituted phenyl acyl group, a fluorine-substituted phenyl acyl group, a chlorine-substituted phenyl acyl group, or a bromine-substituted phenyl acyl group; when R 12 When the alkyl flavinyl group is methyl flavinyl, ethyl flavinyl, isopropyl flavinyl, n-butyl flavinyl, isobutyl flavinyl, tert-butyl flavinyl, cyclopentyl flavinyl, or cyclohexyl flavinyl;

[0054] In this invention, the organic solvent is a solvent commonly used in the field of organic synthesis, including one of methanol, ethanol, isopropanol, dichloromethane, chloroform, dibromomethane, 1,2-dichloroethane, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, toluene, acetonitrile, N,N-dimethylformamide, and dimethyl sulfoxide; preferably chloroform or isopropanol.

[0055] In this invention, the copper salt may be copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, anhydrous copper sulfate, copper acetylacetonate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and cuprous acetate; preferably anhydrous copper sulfate or cuprous bromide.

[0056] In this invention, the iodine source is at least one of sodium iodide, potassium iodide, lithium iodide, ammonium iodide, tetrabutylammonium iodide, and zinc iodide; sodium iodide is preferred.

[0057] In this invention, the molar concentration of compound 9 in the organic solvent in the reaction formula is 0.01 to 5.0 M; for example, 0.1 M.

[0058] In this invention, the molar ratio of compound 9 to the iodine source is 1:1 to 1:3;

[0059] In this invention, compound 9 and sulfur source R 12 The molar ratio of SK is 1:1 to 1:3;

[0060] In this invention, the molar ratio of compound 9 to water is 1:1 to 1:3.

[0061] In this invention, the molar ratio of copper salt to axially chiral bipyridine ligand in the above-mentioned reaction for preparing chiral, diversified substituted 1,1'-bi-2-iodobenzene compounds is 1:5 to 5:1;

[0062] In this invention, the reaction temperature is -40 to 40°C;

[0063] In this invention, the reaction time is 1 to 180 hours;

[0064] In an embodiment of the present invention, after the reaction is completed, a post-processing step is further included. The post-processing step can be a conventional post-processing step in the field of organic synthesis, and the post-processing step includes a column chromatography step.

[0065] The term "er" refers to the enantiomeric ratio.

[0066] The positive and progressive effects of this invention are as follows:

[0067] This invention provides a novel axially chiral bipyridine ligand, characterized by a binaphthalene axially chiral source and bipyridine and bipyridine acyl groups. The synthesis method uses 1,1'-bi-2-naphthol (BINOL), 1,1'-bi-2-naphthylamine (BINAM), substituted BINOL, and substituted BINAM as starting materials, along with halogen-containing bipyridine derivatives and bipyridine carboxylic acid derivatives. Under the action of a palladium catalyst or condensing agent, the binaphthalene axially chiral source undergoes a coupling reaction with bipyridine to construct carbon-oxygen or carbon-nitrogen bonds. The target molecule of this invention has a concise and clear structure, is simple to operate experimentally, and can be prepared on a large scale. It has potential application value in the design of novel axially chiral ligands and the synthesis of axially chiral biaryl compounds.

[0068] The novel axially chiral bipyridine ligand provided by this invention can act as a chiral ligand to form a catalyst with copper salts in a reaction system, catalyzing the asymmetric ring-opening iodination reaction of cyclic diaryl iodonium salts to synthesize a variety of substituted 1,1'-bi-2-iodobenzene compounds, 1,1'-bi-2'-iodo-2-thioester compounds, and 1,1'-bi-2'-iodo-2-phenol compounds. These compounds exhibit good to excellent yields and excellent enantioselectivity (up to 99:1), as well as good substrate versatility (compatible with at least dozens of reaction substrates), showing great promise for industrial applications. Attached Figure Description

[0069] Figure 1 The 1H NMR spectrum of the axially chiral bipyridine ligand 3fa provided in an embodiment of the present invention;

[0070] Figure 2 The 3fa NMR carbon spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0071] Figure 3 The 3cb NMR spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0072] Figure 4 The 3Cb NMR carbon spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0073] Figure 5 The 1H NMR spectrum of the axially chiral bipyridine ligand 6da provided in the embodiments of the present invention;

[0074] Figure 6 The 6da NMR carbon spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0075] Figure 7 The 6cb NMR spectrum of the axially chiral bipyridine ligand provided in this embodiment of the invention;

[0076] Figure 8The 6cb carbon NMR spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0077] Figure 9 The 8ca 1H NMR spectrum of the axially chiral bipyridine ligand provided in an embodiment of the present invention;

[0078] Figure 10 The 8ca carbon NMR spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0079] Figure 11 The 8da 1H NMR spectrum of the axially chiral bipyridine ligand provided in an embodiment of the present invention;

[0080] Figure 12 The 8da carbon NMR spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0081] Figure 13 The 8cb 1H NMR spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0082] Figure 14 The 8cb carbon NMR spectrum of the axially chiral bipyridine ligand provided in the embodiments of the present invention;

[0083] Figure 15 The 10a NMR spectrum of 1,1'-bi-2-iodobenzene compounds provided in the embodiments of the present invention;

[0084] Figure 16 The 10a carbon NMR spectrum of 1,1'-bi-2-iodobenzene compounds provided in the embodiments of the present invention;

[0085] Figure 17 The 1H NMR spectrum of 1,1'-bi-2'-iodine-2-thioester compound 11a provided in the embodiments of the present invention;

[0086] Figure 18 The carbon NMR spectrum of 11a of 1,1'-bi-2'-iodo-2-thioester compound provided in the embodiments of the present invention;

[0087] Figure 19 The 1H NMR spectrum of 1,1'-bi-2'-iodo-2-phenol compound 12a provided in the embodiments of the present invention;

[0088] Figure 20 The carbon NMR spectrum of 12a of 1,1'-bi-2'-iodo-2-phenol compounds provided in the embodiments of the present invention; Detailed Implementation

[0089] The present invention will be further described in detail below through specific embodiments, but this does not limit the scope of the present invention.

[0090] The information on the instruments and experimental materials used in the following embodiments is as follows:

[0091] All chemical reagents were purchased commercially available from companies such as Adamas, Bidex Pharmaceuticals, and Leyan. Thin-layer chromatography (TLC) was performed using SHF254 silica gel plates, and silica gel column chromatography used Nortech silica gel (300-400 mesh). TLC was performed using UV light (254nm). 1 H NMR and 13 C10 NMR was characterized using a Bruker Avance III 400MHz NMR instrument, with deuterated chloroform, deuterated methanol, or deuterated dimethyl sulfoxide as solvents. Chemical shifts are expressed in ppm, and coupling constants are expressed in Hz. 1 In ¹H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, m represents multiplet, and br represents broad peak. 13 In C NMR, δ represents the chemical shift. High-resolution mass spectrometry was performed using a JEOC AccuTOF LC-plus 4G instrument with an ESI ion source, or a Waters GCT Premier with an EI ion source. Enantiomer ratios (er) were determined using Shimadzu LC-20A high-performance liquid chromatography and Daicel Chiralpak or Chiralcel chiral columns.

[0092] Example 1:

[0093]

[0094] Add o-bromobipyridine 2a (235 mg, 1.00 mmol), 1a (443 mg, 1.10 mmol), Pd2(dba)3 (36.6 mg, 4.0 mol%), dppf (44.4 mg, 8.0 mol%), and NaO sequentially to a dry 25 mL Schlenk tube equipped with a magnetic stir bar. t Bu (115 mg, 1.20 mmol) was added, and the reaction system was replaced with N2 three times. The reaction flask was placed in an oil bath at 110 °C and stirred for 24 hours. After the reaction was completed, an appropriate amount of water was added to the reaction solution, and the mixture was extracted three times with EA (3 × 15.0 mL). The organic phases were combined, washed with water 5-6 times, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The mixture was then purified by column chromatography (PE / EA = 20:1) to obtain 493 mg of white solid 3aa, with a yield of 88%. 1H NMR (400MHz, CDCl3): δ8.60(dq,J=4.8,0.8Hz,1H),8.07(d,J=3.2Hz,1H),8.06–8.04(m,1H),8.00(d,J=8 .0Hz,1H),7.81(d,J=8.0Hz,1H),7.80(d,J=8.8Hz,1H),7.73(d,J=8.0Hz,1H),7.69(t,J=7.6Hz,1H),7.61 (ddd,J=8.6,6.6,2.0Hz,1H),7.51(ddd,J=8.4,6.8,1.2Hz,1H),7.42(d,J=8.8Hz,1H),7.33(ddd,J=8.4, 6.8,1.2Hz,1H),7.29(ddd,J=8.0,6.0,2.4Hz,1H),7.24–7.15(m,5H),6.78(d,J=8.0Hz,1H),6.44(s,1H). 13 C NMR (101MHz, CDCl3) δ163.7,155.0,154.0,152.3,151.7,149.3,140.8,137.2,134.3,134.0,131.8,130.6,130.0,129.1,128. 3,128.1,127.2,126.5,126.2,125.8,125.2,124.0(2C),123.4,122.5,120.8,118.8,116.0,115.2,112.4.HRMS(ESI-TOF)m / z Calcd.for C 30 H 21 N2O2 + [M+H] + Found: 441.1598; Found: 441.1596.

[0095] Example 2:

[0096]

[0097] The preparation method is the same as in Example 1. The product is a white solid, 399 mg, with a yield of 88%. 1H NMR (400MHz, CDCl3): δ8.59 (d, J = 4.4Hz, 1H), 8.07 (d, J = 8.0Hz, 1H), 8.02 (d, J = 8. 8Hz,1H),7.99(d,J=8.0Hz,1H),7.95(d,J=7.6Hz,1H),7.88(d,J=9.2Hz,1H),7.77 (d,J=8.0Hz,1H),7.65(ddd,J=8.6,6.6,2.0Hz,1H),7.58(d,J=8.8Hz,1H),7.53(t ,J=7.6Hz,1H),7.49–7.45(m,1H),7.31–7.28(m,3H),7.24–7.19(m,3H),7.03(ddd J=8.4,6.8,1.6Hz,1H),6.55(d,J=8.0Hz,1H),3.57(s,3H). 13 C NMR (101MHz, CDCl3) δ163.3,155.7,155.0,153.8,150.5,145.0,139.7,136.9,134.4,133.9,131.4,129.8,129.0(2C),128.2 ,127.8,126.4,126.2,125.8,125.2,125.0,123.7,123.5,122.8,121.3,118.3,114.9,113.5,111.5,56.4.HRMS(ESI-TOF)m / z Calcd.for C 31 H 23 N2O2 + [M+H] + :455.1754; Found:455.1752.

[0098] Example 3:

[0099]

[0100] The preparation method is the same as in Example 1. The product is a white solid, 423 mg, with a yield of 85%. 1H NMR (400MHz, CDCl3): δ8.61(d,J=4.4Hz,1H),7.96(d,J=8.4Hz,1H),7.95–7.87(m,4H),7.86(d,J= 8.4Hz,1H),7.65(ddd,J=8.4,6.8,1.6Hz,1H),7.61(d,J=8.4Hz,1H),7.50(t,J=8.0Hz,1H),7.43(d dd,J=8.4,6.0,2.0Hz,1H),7.40(dd,J=8.8,1.2Hz,1H),7.36–7.30(m,4H),7.23(ddd,J=7.6,4.0, 0.8Hz,1H),7.11(d,J=7.6Hz,2H),7.03(t,J=7.2Hz,1H),6.93–6.83(m,3H),6.36(d,J=8.0Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.5,155.6,153.6,150.1,148.9,141.8,140.2,139.8,136.8,135.0,133.1,132.7,130.8(2C),129.1,128.6,128 .4,128.3,128.2,127.8,127.5,127.4,126.9,126.6,126.4,126.0,125.7,125.0,123.7,122.4,121.4,115.0,111.7.HRMS(ESI-TOF)m / z Calcd.for C 36 H 25 N2O + [M+H] + Found: 501.1961; Found: 501.1954.

[0101] Example 4:

[0102]

[0103] The preparation method is the same as in Example 1. The product is a white solid, 453 mg, with a yield of 88%. 1H NMR (400MHz, CDCl3): δ8.61(dq,J=4.8,0.8Hz,1H),7.96–7.93(m,3H),7.90(d,J=8.8Hz,1H),7.87(d,J=8.0Hz,2 H),7.64(ddd,J=8.4,6.8,1.6Hz,1H),7.59(d,J=8.4Hz,1H),7.50(t,J=8.0Hz,1H),7.46(ddd,J=8.0,6.4,1.6Hz, 1H),7.43(d,J=8.8Hz,1H),7.37–7.31(m,3H),7.28(d,J=8.4Hz,1H),7.22(ddd,J=7.6,4.8,1.2Hz,1H),7.05(dd d,J=8.4,6.8,1.2Hz,1H),6.93(d,J=8.4Hz,2H),6.67(d,J=8.0Hz,2H),6.38(dd,J=8.0,0.4Hz,1H),1.89(s,3H). 13 C NMR (101MHz, CDCl3) δ162.4,155.6,153.3,149.8,148.9,140.1,139.6,138.8,136.8,136.0,135.1,133.2,132.6,130.8,130.7,128.9,128 .5,128.3(2C),128.2,127.8,127.3,127.1,126.7,126.6,126.0,125.5,125.0,123.6,122.8,121.3,114.8,111.6,20.8.HRMS(ESI-TOF)m / z Calcd.for C 37 H 27 N2O + [M+H] + :515.2118;Found:515.2115.

[0104] Example 5:

[0105]

[0106] The preparation method is the same as in Example 1. The product is a white solid, 449 mg, with a yield of 87%. 1H NMR (400MHz, CDCl3): δ8.60(dq,J=4.8,0.8Hz,1H),8.00–7.92(m,3H),7.89(d,J=8.8Hz,1H),7.87(d,J=8.0Hz,2H),7.6 3(ddd,J=8.6,6.6,2.0Hz,1H),7.60(d,J=8.4Hz,1H),7.50(t,J=7.6Hz,1H),7.45(ddd,J=8.0,6.4,2.0Hz,1H),7.39(d, J=8.8Hz,1H),7.37–7.33(m,2H),7.33–7.29(m,2H),7.22(ddd,J=7.6,4.8,1.2Hz,1H),7.06(ddd,J=8.4,6.8,1.6Hz,1H ),6.86(s,1H),6.83(d,J=7.6Hz,1H),6.73(t,J=7.6Hz,1H),6.60(d,J=7.6Hz,1H),6.30(d,J=8.0Hz,1H),1.95(s,3H). 13 C NMR (101MHz, CDCl3) δ162.5,155.6,153.5,149.9,148.9,141.7,140.2,13 9.6,136.9,136.7,135.2,133.2,132.7,130.8,130.7,130.1,128.5,128.4 ,128.3,128.2,127.8,127.3(2C),127.2,127.0,126.7,126.6,126.1(2C), 125.6,125.0,123.6,122.5,121.4,114.9,111.6,21.3.HRMS(ESI-TOF)m / z Calcd.for C 37 H 27 N2O + [M+H] + :515.2118; Found:515.2120.

[0107] Example 6:

[0108]

[0109] The preparation method is the same as in Example 1, yielding a white solid, 490 mg, with a yield of 88%. 1H NMR (400MHz, CDCl3): δ8.60(d,J=4.8Hz,1H),8.03(d,J=8.0Hz,1H),7.94(d,J=8.0Hz,2H),7. 92(d,J=6.8Hz,1H),7.89(d,J=9.2Hz,1H),7.84(d,J=8.0Hz,1H),7.66(ddd,J=8.8,6.8,1.6H z,1H),7.61–7.59(m,1H),7.46–7.42(m,2H),7.39–7.36(m,1H),7.34–7.28(m,4H),7.22(dd, J=7.2,4.8Hz,1H),7.07–6.96(m,5H),6.16(dd,J=8.0,2.0Hz,1H),1.13(s,6H),1.12(s,3H). 13 C NMR (101MHz, CDCl3)δ 13 C NMR (101MHz, CDCl3) δ162.7,155.6,153.7,150.2,149.1,149.0,140.0,1 39.7,138.9,136.9,135.1,133.2,132.7,130.8,130.6,128.9,128.7(2C) ,128.3,128.1,127.8,127.3,127.1,126.7,126.6,126.0,125.5,125.0, 124.6,123.7,122.1,121.3,115.1,111.6,34.3,31.3.HRMS(ESI-TOF)m / z Calcd.for C 40 H 33 N2O + [M+H] + :557.2587; Found:557.2596.

[0110] Example 7:

[0111]

[0112] The preparation method is the same as in Example 1. The product is a white solid, 484 mg, with a yield of 87%. 1H NMR (400MHz, CDCl3): δ8.63(d,J=4.8Hz,1H),7.98(d,J=8.4Hz,1H),7.96–7.93(m,3H),7.89(d,J=8 .8Hz,1H),7.88(d,J=8.4Hz,1H),7.68(dd,J=8.4,2.0Hz,1H),7.64(ddd,J=8.6,6.6,2.0Hz,1H),7.4 9(d,J=7.6Hz,1H),7.46–7.33(m,3H),7.37(d,J=7.2Hz,2H),7.34(d,J=6.8Hz,1H),7.22(ddd,J=7. 2,4.8,0.8Hz,1H),7.12(s,1H),7.06–6.96(m,4H),6.27(d,J=8.0Hz,1H),0.88(s,3H),0.87(s,6H). 13 C NMR (101MHz, CDCl3) δ162.6,155.6,153.6,150.0,149.8,148.9,141.3,140 .7,139.7,136.8,135.3,133.2,132.7,130.9(2C),128.5,128.3(2C),128.2 ,127.8,127.6,127.4,127.3,126.7(2C),126.6,126.3,126.0,125.6,125. 0,123.6,123.2,122.4,121.4,115.0,111.6,34.3,31.0.HRMS(ESI-TOF)m / z Calcd.for C 40 H 33 N2O + [M+H] + :557.2587; Found:557.2589.

[0113] Example 8:

[0114]

[0115] The preparation method is the same as in Example 1, yielding a white solid of 526 mg with a yield of 97%. 1H NMR (400MHz, CDCl3): δ8.62–8.61(m,1H),8.00(d,J=8.0Hz,1H),7.96(d,J=7.6Hz,1H),7.95(d,J=8.4Hz,1H), 7.93(d,J=8.4Hz,1H),7.90(d,J=9.2Hz,1H),7.86(d,J=8.0Hz,1H),7.68–7.61(m,2H),7.49–7.46(m,1H),7.4 5–7.42(m,1H),7.41(d,J=8.8Hz,1H),7.37(d,J=8.4Hz,1H),7.34–7.30(m,3H),7.22(ddd,J=7.2,4.8,1.2Hz, 1H),7.07–7.02(m,3H),6.82(d,J=8.0Hz,2H),6.25(d,J=8.0Hz,1H),2.66–2.55(m,1H),1.06(d,J=6.8Hz,6H). 13 C NMR (101MHz, CDCl3) δ162.6,155.6,153.6,150.1,149.0,146.7,140.1,13 9.7,139.3,136.8,135.1,133.2,132.6,130.7,130.6,129.1,128.6,128.6 ,128.3,128.1,127.8,127.3,127.1,126.7,126.6(2C),125.7,125.5,125. 0,123.7,122.3,121.3,115.0,111.6,33.4,24.0,23.7.HRMS(ESI-TOF)m / z Calcd.for C 39 H 31 N2O + [M+H] + :543.2431; Found:543.2434.

[0116] Example 9:

[0117]

[0118] The preparation method is the same as in Example 1, yielding a white solid of 524 mg with a yield of 91%. 1H NMR (400MHz, CDCl3): δ8.52 (dq, J=4.8, 0.8Hz, 1H), 7.98 (d, J=8.4Hz, 1H), 7.95 (d, J=7. 2Hz,1H),7.94(d,J=8.4Hz,1H),7.89(d,J=9.2Hz,1H),7.88(d,J=8.4Hz,1H),7.85(d,J= 8.0Hz,1H),7.63(d,J=8.4Hz,1H),7.53–7.44(m,3H),7.41(d,J=8.8Hz,1H),7.39–7.32 (m,3H),7.31–7.28(m,5H),7.25–7.20(m,1H),7.16–7.05(m,6H),6.34(d,J=8.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.5,155.4,153.5,150.0,148.8,140.9,140.4,139. 8,139.7,138.7,136.7,135.1,133.3,132.8,130.9,130.8,129.6,128.6(2C ),128.4(2C),128.3,127.9,127.3,127.0,126.9,126.7(2C),126.6,126.2, 126.1,125.7,125.1,123.6,122.6,121.2,115.0,111.6.HRMS(ESI-TOF)m / z Calcd.for C 42 H 29 N2O + [M+H] + :577.2274; Found:577.2268.

[0119] Example 10:

[0120]

[0121] The preparation method is the same as in Example 1, yielding a white solid, 449 mg, with a yield of 85%. 1H NMR (400MHz, CDCl3): δ8.61(dq,J=4.8,0.8Hz,1H),7.95(d,J=8.0Hz,3H),7.89(d,J=8.8Hz,1H),7.88(d,J=8.0H z,1H),7.82(d,J=8.0Hz,1H),7.63(ddd,J=8.6,7.0,2.0Hz,1H),7.59(d,J=8.4Hz,1H),7.50(t,J=7.8Hz,1H),7.4 6(ddd,J=8.8,6.8,2.4Hz,1H),7.40(d,J=9.2Hz,1H),7.38–7.33(m,3H),7.30(d,J=8.4Hz,1H),7.22(ddd,J=7.6, 4.8,1.2Hz,1H),7.08(ddd,J=8.4,6.8,1.2Hz,1H),6.58(s,2H),6.34(s,1H),6.28(d,J=7.6Hz,1H),1.85(s,6H). 13 CNMR(101MHz, CDCl3)δ162.5,155.6,153.3,149.7,148.9,141.5,140.2,139.5,136.6(2C),135.4,133.3,132.7,130.7(2C),128.5,128.3 ,128.2(2C),128.1,127.9,127.3,127.1,126.8,126.6,126.1,125.6,125.0,123.6,122.6,121.4,114.8,111.6,21.2.HRMS(ESI-TOF)m / z Calcd.for C 38 H 29 N2O + [M+H] + :529.2274; Found:529.2276.

[0122] Example 11:

[0123]

[0124] The preparation method is the same as in Example 1, yielding a white solid of 545 mg with a yield of 89%. 1H NMR (400MHz, CDCl3): δ8.60–8.58(m,1H),8.00–7.96(m,2H),7.93–7.91(m,1H),7.88(d,J=8 .4Hz,1H),7.85(d,J=8.4Hz,1H),7.83(d,J=9.6Hz,1H),7.72–7.69(m,1H),7.65(ddd,J=8.6, 6.6,2.0Hz,1H),7.46–7.40(m,2H),7.37(d,J=8.8Hz,2H),7.34–7.25(m,3H),7.22(ddd,J=7. 2,4.8,1.2Hz,1H),7.09–6.98(m,4H),6.15(dd,J=8.0,2.0Hz,1H),1.00(s,9H),0.99(s,9H). 13 CNMR(101MHz,CDCl3)δ162.9,155.6,153.8,150.3,149.7,149.0,141.1, 140.9,139.8,136.8,135.4,133.2,132.6,130.9(2C),128.6,128.4,128 .2,128.1,127.8,127.4,127.1,126.7(2C),125.9,125.5,124.9,123.8, 123.7,121.8,121.3,120.2,115.2,111.9,34.6,31.3.HRMS(ESI-TOF)m / z Calcd.for C 44 H 41 N2O + [M+H] + :613.3213;Found:613.3211.

[0125] Example 12:

[0126]

[0127] The preparation method is the same as in Example 1. The product is a white solid, 561 mg, with a yield of 86%. 1H NMR (400MHz, CDCl3): δ8.54–8.52(m,1H),8.10(d,J=8.0Hz,1H),8.03(d,J=8.8Hz,1H),7.98(d,J= 9.2Hz,1H),7.94(d,J=8.0Hz,1H),7.76(d,J=8.4Hz,1H),7.71(d,J=7.6Hz,1H),7.65–7.61(m,1H) ,7.58(d,J=8.0,6.4,1.2Hz,1H),7.51(d,J=8.4Hz,1H),7.45–7.39(m,4H),7.34(t,J=7.6Hz,1H), 7.29–7.25(m,8H),7.19–7.16(m,2H),7.10–7.07(m,2H),7.00–6.97(m,4H),6.30(d,J=8.4Hz,1H). 13 C NMR (101MHz, CDCl3) δ162.2,155.2,153.2,149.8,148.6,142.3,140.8,140 .6,139.8,139.6,136.3,135.8,133.4,133.0,131.2,131.0,128.6(2C),128 .5,128.2(2C),128.0,127.3,127.2(2C),127.1(2C),127.0,126.9,126.4, 125.9,125.2,124.0,123.5,123.1,121.7,115.1,111.4.HRMS(ESI-TOF)m / z Calcd.for C 48 H 33 N2O + [M+H] + Found: 653.2587; Found: 653.2579.

[0128] Example 13:

[0129]

[0130] The preparation method is the same as in Example 1. The product is a white solid, 372 mg, with a yield of 85%. 1H NMR (400MHz, CDCl3): δ8.59(dq,J=4.8,0.8Hz,1H),8.03(d,J=8.8Hz,1H),8.00–7.97(m,2H),7.96(d,J= 7.6Hz,1H),7.79(dd,J=7.6,1.6Hz,2H),7.64(ddd,J=8.4,6.8,1.6Hz,1H),7.57(d,J=8.8Hz,1H),7.53(d ,J=8.0Hz,1H),7.50–7.46(m,1H),7.38(d,J=8.4Hz,1H),7.31–7.27(m,3H),7.21(ddd,J=7.6,4.8,1.2Hz ,1H),7.17(d,J=8.4Hz,1H),7.02(ddd,J=8.0,6.4,1.2Hz,1H),6.49(dd,J=8.0,0.4Hz,1H),2.10(s,3H). 13 C NMR (101MHz, CDCl3) δ163.0,155.6,153.6,150.2,149.0,139.9,136.9,135.4,134.0,133.2,132.0,131.4(2C),128.8,128.6,12 8.3,127.8,127.7,127.5,126.6,126.4,126.0,125.7,125.3,124.8,123.7,123.0,121.1,115.1,111.7,20.6.HRMS(ESI-TOF)m / z Calcd.for C 31 H 23 N2O + [M+H] + Found: 439.1805; Found: 439.1808.

[0131] Example 14:

[0132]

[0133] The preparation method is the same as in Example 1. The product is a white solid, 236 mg, with a yield of 93%. 1H NMR (400MHz, CDCl3): δ7.96(d,J=8.4Hz,2H),7.88(d,J=8.4Hz,2H),7.87(d,J=7.6Hz,2H) ,7.85(d,J=8.8Hz,2H),7.60(d,J=8.4Hz,2H),7.46(dd,J=7.6,0.8Hz,2H),7.42–7.38(m, 2H),7.37–7.31(m,8H),7.28(d,J=0.8Hz,2H),7.26(d,J=2.0Hz,2H),7.10(dt,J=6.4,2.0 Hz,4H),7.04(ddd,J=8.4,6.8,1.2Hz,2H),6.93–6.86(m,6H),6.26(dd,J=8.0,0.8Hz,2H). 13 C NMR (101MHz, CDCl3) δ162.3,153.1,150.2,141.9,140.2,139.5,134.8,133.2,132.7,130.9,130.7,129.2,128.6,128. 4,128.3,128.1,127.8,127.5,127.4,126.7,126.5(2C),126.1,125.7,125.0,122.1,115.4,111.5.HRMS(ESI-TOF)m / z Calcd.for C 62 H 41 N2O2 + [M+H] + :845.3163; Found:845.3157.

[0134] Example 15:

[0135]

[0136] A magnetic stir bar was added to a 100 mL Schlenk tube, and compound 1m (0.29 g, 1.0 mmol), compound 5a (0.24 g, 1.2 mmol), condensation reagent HATU (0.76 g, 2.0 mmol), and triethylamine (280.0 μL, 2.0 mmol) were added sequentially. 10 mL of DCM solution was added, and the reaction was carried out at 25 °C for 12 hours. The reaction was monitored by TLC. After the starting material was converted, the reaction was quenched with water, the organic phase was separated, and the aqueous phase was extracted three times with DCM. The organic phases were combined, dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporation under reduced pressure. 410 mg of white solid 6aa was obtained by silica gel column chromatography (PE:EA = 8:1), with a yield of 91%. 1H NMR (400MHz, CDCl3) δ8.61(d,J=4.8Hz,1H),8.46(d,J=8.0Hz,1H),8.09(d,J=9.2Hz, 1H),8.01(d,J=8.0Hz,1H),7.98(dd,J=8.0,1.2Hz,1H),7.84(d,J=8.4Hz,1H),7.79( d,J=8.4Hz,1H),7.74(td,J=8.0,2.0Hz,1H),7.70–7.66(m,2H),7.51(ddd,J=8.0,6. 8,1.2Hz,1H),7.45–7.38(m,3H),7.37–7.34(m,2H),7.33–7.27(m,3H),2.18(s,3H). 13 C NMR (101MHz, CDCl3) δ163.4,156.3,155.1,149.0,146.7,146.7,137.7,137.1,135.6,133.4,133.2,132.1(2C),130.7,12 9.4,128.7,128.4,128.1,127.9,127.0,126.4,126.0(2C),125.0(2C),124.2(2C),121.9,121.7,20.5.HRMS(ESI-TOF)m / z Calcd.for C 32 H 23 N2O2 + [M+H] + :467.1754;Found:467.1746.

[0137] Example 16:

[0138]

[0139] The preparation method is the same as in Example 15, resulting in a white solid, 213 mg, with a yield of 88%. 1 H NMR (400MHz, CDCl3) δ8.63–8.61(m,1H),8.48(dd,J=8.0Hz,0.8Hz,1H),8.07(d,J=8.8Hz,1H),7.99(dt,J=8.0,1.2Hz,2H),7.91(d, J=8.8Hz,1H),7.84(dt,J=7.6,1.2Hz,1H),7.74–7.69(m,3H),7.52–7.47(m,2H),7.37–7.32(m,4H),7.30–7.27(m,3H),3.70(s,3H). 13C NMR (101MHz, CDCl3) δ163.4,156.3,155.2,155.1,149.0,147.1,147.0,137.7,137.0,134.0,133.8,132.0,130.1,129.2,129.1,128.4,127 .9,126.9,126.6,126.4,125.7,125.5,125.2,125.0,124.2,124.1,123.7,121.9,121.8,117.8,113.7,56.7.HRMS(ESI-TOF)m / zCalcd.for C 32 H 23 N2O3 + [M+H] + :483.1703; Found:483.1699.

[0140] Example 17:

[0141]

[0142] The preparation method is the same as in Example 15, resulting in a white solid, 200 mg, with a yield of 75%. 1 H NMR (400MHz, CDCl3) δ8.67–8.63(m,1H),8.53(dd,J=8.0,0.8Hz,1H),8.10(d,J=8.0Hz,1H),7.98( d,J=8.4Hz,1H),7.95(d,J=8.4Hz,1H),7.93(d,J=7.6Hz,1H),7.92(d,J=9.2Hz,1H),7.77(t,J=8.0 Hz,1H),7.74(td,J=7.6,1.6Hz,1H),7.62(d,J=8.4Hz,1H),7.59(d,J=8.8Hz,2H),7.49–7.46(m,1 H),7.46–7.40(m,2H),7.38–7.31(m,3H),7.30–7.28(m,1H),7.17–7.14(m,2H),7.10–7.02(m,3H). 13C NMR (101MHz, CDCl3) δ162.9,156.3,155.1,149.1,146.9(2C),141.6,140.3,137.7,137.0,134.2,133.0,132.8,131.4,130.3,129.2,129.0,1 28.5,128.2(2C),127.9,127.6,127.5,127.0,126.8(2C),126.7,126.6,125.9,125.6,125.1,124.3,124.2,121.8,121.5.HRMS(ESI-TOF)m / z Calcd.for C 37 H 25 N2O2 + [M+H] + Found: 529.1911; Found: 529.1902.

[0143] Example 18:

[0144]

[0145] The preparation method is the same as in Example 15, resulting in a white solid, 231 mg, with a yield of 82%. 1 H NMR (400MHz, CDCl3) δ8.64–8.63(m,1H),8.52(dd,J=8.0,0.8Hz,1H),8.13(dd,J=8.0,1.2Hz,1H),7.96(d, J=8.4Hz,1H),7.95(d,J=9.2Hz,1H),7.90(d,J=8.4Hz,2H),7.77(d,J=8.0Hz,1H),7.75–7.72(m,1H),7.63( dd,J=8.4,0.8Hz,1H),7.59(dd,J=8.8,0.8Hz,1H),7.56(dt,J=7.6,0.8Hz,1H),7.47–7.41(m,2H),7.37(d, J=8.4Hz,1H),7.35(d,J=8.0Hz,1H),7.32–7.27(m,3H),7.09–7.06(m,2H),7.06–7.03(m,2H),1.20(s,9H). 13C NMR (101MHz, CDCl3) δ162.8,156.3,155.1,149.5,149.1,147.0,146.9,14 0.2,138.5,137.7,137.0,134.3,133.1,132.7,131.5,130.1,129.1,128.7 ,128.5(2C),128.2,127.8,127.7,127.0,126.7(2C),126.6,125.8,125.6 ,125.1,124.6,124.3,124.2,121.8,121.6,34.4,31.3.HRMS(ESI-TOF)m / z Calcd.for C 41 H 33 N2O2 + [M+H] + :585.2537; Found:585.2544.

[0146] Example 19:

[0147]

[0148] The preparation method is the same as in Example 15, resulting in a white solid, 344 mg, with a yield of 85%. 1 H NMR (400MHz, CDCl3) δ8.08(d,J=8.8Hz,2H),7.99(dt,J=8.0,1.2Hz,4H),7.88(d,J=9.2Hz,2H),7.82(d,J=7 .6Hz,2H),7.70(d,J=8.8Hz,2H),7.61(t,J=8.0Hz,2H),7.52–7.47(m,4H),7.36–7.28(m,12H),3.67(s,6H). 13 C NMR (101MHz, CDCl3) δ163.3,155.2,155.1,147.0,146.8,137.7,134.0,133.8,132.0,130.1,129.2,129.0,128.4,127.9, 126.9,126.7,126.4,125.8,125.6,125.4,125.1,124.8,123.7,121.9,117.7,113.6,56.7.HRMS(ESI-TOF)m / zCalcd.for C 54 H 37 N2O6 + [M+H] + :809.2646; Found:809.2641.

[0149] Example 20:

[0150]

[0151] The preparation method is the same as in Example 15. The product is a white solid, 362 mg, with a yield of 80%. 1 H NMR (400MHz, CDCl3) δ8.13(dd,J=7.6,1.2Hz,2H),7.97(d,J=8.0Hz,2H),7.95(d,J=9.2Hz,2H),7.93(d,J =8.4Hz,2H),7.91(d,J=8.8Hz,2H),7.69(t,J=8.0Hz,2H),7.61(d,J=8.4Hz,2H),7.60(dd,J=8.0,0.8Hz,2 H),7.58(d,J=8.8Hz,2H),7.50–7.47(m,2H),7.46–7.43(m,2H),7.43–7.37(m,3H),7.34(dd,J=6.4,1.6H z,4H),7.31–7.29(m,1H),7.14–7.12(m,2H),7.11(d,J=2.0Hz,2H),7.08–7.06(m,2H),7.05–7.01(m,4H). 13 C NMR (101MHz, CDCl3) δ162.8,155.1,146.9,146.7,141.5,140.3,137.7,134.2,133.0,132.7,131.5,130.3,129.2,129.0,128.6 ,128.3,128.2,127.9,127.6,127.5,127.0,126.9,126.8,126.7,126.6,125.9,125.7,125.5,124.8,121.5.HRMS(ESI-TOF)m / z Calcd.for C 54 H 37 N2O6 + [M+H] + :809.2646; Found:809.2641.

[0152] Example 21:

[0153]

[0154] The preparation method is the same as in Example 15, resulting in a white solid, 170 mg, with a yield of 89%. 1H NMR (400MHz, CDCl3) δ9.94(s,1H),9.17(dd,J=9.2,1.6Hz,1H),8.60(dd,J=4.8,0.8Hz,1H),8.48(dd,J=8.0,0.8Hz,1H),8.2 7(dd,J=8.0,0.8Hz,1H),8.12(d,J=9.2Hz,1H),8.05(d,J=8.4Hz,1H),8.00(d,J=8.4Hz,1H),7.96(d,J=8.0Hz,1H),7.90(t, J=8.0Hz,1H),7.75(td,J=7.6,2.0Hz,1H),7.61(d,J=8.4Hz,1H),7.47–7.44(m,1H),7.43–7.40(m,1H),7.32(ddd,J=7.6,4. 8,1.2Hz,1H),7.28(s,1H),7.27(s,1H),7.26–7.22(m,1H),6.96(d,J=8.4Hz,1H),6.76(dd,J=8.0,0.8Hz,1H),2.16(s,3H). 13 C NMR (101MHz, CDCl3) δ162.3,154.4(2C),149.2,149.1,138.5,137.0,136.6,134.2,133.1,132.8,132.4,131.1,131.0,129.2,129.1 ,128.7,128.3,128.0,127.1,126.7,125.8,125.7,125.5,125.0,124.1,123.9,123.7,122.5,120.5,119.8,20.3.HRMS(ESI-TOF)m / z Calcd.for C 32 H 23 N3ONa + [M+Na] + Found: 488.1733; Found: 488.1737.

[0155] Example 22:

[0156]

[0157] The preparation method is the same as in Example 15, resulting in a white solid, 170 mg, with a yield of 72%. 1H NMR (400MHz, CDCl3) δ10.02(s,1H),9.10(d,J=9.2Hz,1H),8.61(dd,J=4.8,1.6Hz,1H),8.4 7(d,J=8.0Hz,1H),8.27(d,J=7.6Hz,1H),8.13(d,J=9.2Hz,1H),8.08(d,J=9.2Hz,1H),7.9 6(d,J=8.4Hz,1H),7.94–7.90(m,2H),7.74(td,J=7.6,2.0Hz,1H),7.51(d,J=8.8Hz,1H),7 .41(d,J=7.2Hz,1H),7.38–7.35(m,1H),7.34–7.27(m,2H),7.25–7.20(m,2H),3.71(s,3H). 13 C NMR (101MHz, CDCl3) δ162.2,155.7,154.6,154.4,149.5,149.1,138.5,136.9,134.8,134.1,133.2,131.1,130.7,129.3,129.1,128.3,128 .1,127.6,126.5,125.7,125.3,124.8,124.4,124.1,123.7,122.6,121.5,120.6,120.0,117.7,114.1,56.9.HRMS(ESI-TOF)m / zCalcd.for C 32 H 24 N3O2 + [M+H] + Found: 482.1863; Found: 482.1860.

[0158] Example 23:

[0159]

[0160] The preparation method is the same as in Example 15, resulting in a white solid, 201 mg, with a yield of 76%. 1H NMR(400MHz, CDCl3)δ9.98(s,1H),8.87(d,J=9.2Hz,1H),8.65–8.63(m,1H),8.52(dd,J=7.6,1.2Hz,1H),8.23(dd, J=7.6,1.2Hz,1H),8.18(d,J=8.8Hz,1H),8.07(dd,J=8.0,1.2Hz,1H),7.97–7.92(m,2H),7.87(d,J=8.4Hz,1H),7. 76(td,J=7.6,2.0Hz,1H),7.72(d,J=8.8Hz,1H),7.54(ddd,J=8.4,6.4,2.0Hz,1H),7.39(dd,J=6.4,1.2Hz,1H),7. 36–7.31(m,3H),7.28–7.24(m,1H),7.13(d,J=8.4Hz,1H),7.02–6.98(m,1H),6.96–6.94(m,2H),6.93–6.89(m,3H). 13 CNMR(101MHz, CDCl3)δ161.9,154.5(2C),149.3,149.2,141.4,140.8,138.6,137.0,134.6,133.8,133.1(2C),130.6(2C),129.1(2C),128.8 ,128.5,128.2,128.1,127.7,127.5,127.1,126.8,126.7,126.6,126.1,124.8,124.2,123.8,123.7,122.5,120.7,119.7.HRMS(ESI-TOF)m / z Calcd.for C 37 H 25 N3ONa + [M+Na] + :550.1890; Found:550.1889.

[0161] Example 24:

[0162]

[0163] The preparation method is the same as in Example 15. The product is a white solid, 208 mg, with a yield of 84%. 1H NMR (400MHz, CDCl3) δ10.10(s,1H),9.07(d,J=8.8Hz,1H),8.61(dd,J=4.8,1.2Hz,1H),8.48(d,J=8.0Hz,1H),8 .28(dd,J=7.6,1.2Hz,1H),8.08(d,J=8.8Hz,1H),8.03(d,J=8.8Hz,1H),7.93(t,J=8.0Hz,3H),7.73(td,J=7.6 ,1.6Hz,1H),7.48(d,J=8.8Hz,1H),7.41(td,J=6.8,1.2Hz,1H),7.36–7.31(m,2H),7.24(dd,J=6.8,1.2Hz,1H) ,7.20(dd,J=6.4,1.2Hz,1H),7.17(d,J=8.4Hz,1H),7.14(d,J=8.8Hz,1H),6.89(d,J=7.6Hz,1H),2.44(s,6H). 13 C NMR (101MHz, CDCl3) δ162.3,154.5(2C),150.9,149.5,149.1,138.5,136.9,134.4,134.1,133.4,131.2,129.9,129.6,128.9,128.3,127 .9,127.1,126.5,126.3,125.2,124.8,124.4,124.1(2C),123.7,122.5,121.0,120.9,120.4,120.0,43.3.HRMS(ESI-TOF)m / zCalcd.for C 33 H 27 N4O + [M+H] + Found: 495.2179; Found: 495.2178.

[0164] Example 25:

[0165]

[0166] The preparation method is the same as in Example 15. The product is a white solid, 399 mg, with a yield of 89%. 1H NMR (400MHz, CDCl3) δ9.88(s,2H),8.87(d,J=8.8Hz,2H),8.27(d,J=8.0Hz,2H),8.17(d,J= 8.4Hz,2H),8.05(d,J=8.4Hz,2H),7.96(d,J=8.8Hz,2H),7.87(t,J=8.0Hz,4H),7.72(d,J=8 .4Hz,2H),7.51(ddd,J=8.0,6.4,1.6Hz,2H),7.40–7.33(m,4H),7.33–7.28(m,2H),7.26–7 .22(m,2H),7.10(d,J=8.4Hz,2H),7.03–6.99(m,2H),6.97–6.95(m,6H),6.93–6.89(m,4H). 13 CNMR (101MHz, CDCl3) δ161.6,152.8,149.4,141.4,140.8,138.6,134.5,133.7,133.0,130.7,130.5,129.2,129.1,128 .7,128.5,128.2,128.1,127.7,127.5,127.2,126.7(2C),126.0,124.9,123.7,123.2,122.8,119.5.HRMS(ESI-TOF)m / z Calcd.for C 64 H 42 N4O2Na + [M+Na] + :921.3200;Found:921.3201.

[0167] Example 26: Optimization of synthetic conditions for 1,1'-bi-2-iodobenzene compounds (solvent screening)

[0168]

[0169]

[0170] Unless otherwise stated, the reaction is carried out in 1 mL of solvent on a 0.1 mmol scale.

[0171] Example 27: Optimization of synthetic conditions for 1,1'-bi-2-iodobenzene compounds (screening of copper salts)

[0172]

[0173]

[0174] Unless otherwise stated, the reaction was carried out in 1 mL of CHCl3 solvent at a scale of 0.1 mmol. Example 28: Optimization of synthetic conditions for 1,1'-bi-2-iodobenzene compounds (screening of ligand ratios).

[0175]

[0176]

[0177] Unless otherwise stated, the reaction was carried out in 1 mL of CHCl3 solvent at a scale of 0.1 mmol. Example 29: Optimization of synthesis conditions for 1,1'-bi-2-iodobenzene compounds (screening of iodine source).

[0178]

[0179]

[0180] Unless otherwise stated, the reaction was carried out in 1 mL of CHCl3 solvent at a scale of 0.1 mmol. Example 30: Optimization of synthesis conditions (temperature screening) for 1,1'-bi-2-iodobenzene compounds.

[0181]

[0182]

[0183] Unless otherwise stated, the reaction was carried out in 1 mL of CHCl3 solvent at a scale of 0.1 mmol. Example 31: Optimization of synthetic conditions for 1,1'-bi-2-iodobenzene compounds (ligand screening).

[0184]

[0185]

[0186] Unless otherwise stated, the reaction is carried out in 1 mL of CHCl3 solvent at a scale of 0.1 mmol.

[0187] Example 32: Asymmetric ring-opening synthesis of diverse substituted 1,1'-bi-2-iodobenzene compounds from diaryliodonium salts containing different substituents

[0188]

[0189] CuSO4 (0.40 mg, 0.0025 mmol) and ligand 3fa (1.7 mg, 0.0030 mmol) were added to a dry reaction tube, and nitrogen was added three times to purge the mixture. 0.5 mL of CHCl3 was added as a solvent, and the reaction tube was placed in a metal heating block at 25 °C and pre-stirred for 30 min to prepare the complex. Under a nitrogen atmosphere, cyclic diaryliodonium salt 9 (0.05 mmol) and NaI (0.06 mmol) were added, and the reaction was carried out at 0 °C for 36 h. After the reaction was completed, the target product was obtained by column chromatography (PE). The enantiomeric excess value of the product was analyzed by high performance liquid chromatography. The experimental results for each substituent of 1,1'-bi-2-iodobenzene are shown in the table below.

[0190]

[0191]

[0192] Example 48: Optimization of synthetic conditions for 1,1'-bi-2'-iodo-2-thioester compounds (screening of copper salts)

[0193]

[0194]

[0195]

[0196] Unless otherwise stated, the reaction was carried out in 1 mL of CH2Cl2 solvent at a scale of 0.1 mmol. Example 49: Optimization of synthesis conditions for 1,1'-bi-2'-iodine-2-thioester compounds (solvent screening).

[0197]

[0198]

[0199] Unless otherwise stated, the reaction is carried out in 1 mL of solvent on a 0.1 mmol scale.

[0200] Example 50: Optimization of synthetic conditions for 1,1'-bi-2'-iodo-2-thioester compounds (ligand screening)

[0201]

[0202]

[0203]

[0204] Unless otherwise stated, the reaction is carried out in 1 mL of CHCl3 solvent at a scale of 0.1 mmol.

[0205] Example 51: Asymmetric ring-opening synthesis of diverse substituted 1,1'-bi-2'-iodo-2-thioester compounds from diaryl iodonium salts containing different substituents

[0206]

[0207] CuSO4 (0.40 mg, 0.0025 mmol) and ligand 3fa (1.7 mg, 0.0030 mmol) were added to a dry reaction tube, and nitrogen was purged three times. 0.5 mL of CHCl3 was added as a solvent, and the reaction tube was placed in a metal heating block at 25 °C and pre-stirred for 30 min to prepare the complex. Under a nitrogen atmosphere, the starting material, cyclic diaryliodonium salt 9 (0.05 mmol) and potassium thioacetate (0.06 mmol), were added, and the reaction was carried out at -20 °C for 36 h. After the reaction, the target product was obtained by column chromatography (PE). The enantiomeric excess value of the product was analyzed by high performance liquid chromatography. The experimental results of the obtained 1'-bi-2'-iodo-2-thioesters with various substituents are shown in the table below.

[0208]

[0209]

[0210] Example 62: Synthesis of diverse substituted 1,1'-bi-2'-iodo-2-thioester compounds from sulfur sources containing different substituents

[0211]

[0212] CuSO4 (0.40 mg, 0.0025 mmol) and ligand 3fa (1.7 mg, 0.0030 mmol) were added to a dry reaction tube, and nitrogen was purged three times. 0.5 mL of CHCl3 was added as a solvent, and the reaction tube was placed in a metal heating block at 25 °C and pre-stirred for 30 min to prepare the complex. Under a nitrogen atmosphere, the starting material, cyclic diaryl iodonium salt 9a (0.05 mmol) and potassium thiocarboxylate with different substituents (0.06 mmol) were added, and the reaction was carried out at -20 °C for 36 h. After the reaction, the target product was obtained by column chromatography (PE). The enantiomeric excess value of the product was analyzed by high performance liquid chromatography. The experimental results of the obtained 1'-bi-2'-iodo-2-thioesters with different substituents are shown in the table below.

[0213]

[0214]

[0215] Example 78: Optimization of synthetic conditions for 1,1'-bi-2'-iodo-2-phenol compounds (screening of copper salts)

[0216]

[0217]

[0218]

[0219] Unless otherwise stated, the reaction was carried out in 2 mL of CH2Cl2 solvent at a scale of 0.1 mmol. Example 79: Optimization of synthesis conditions for 1,1'-bi-2'-iodo-2-phenol compounds (solvent screening).

[0220]

[0221]

[0222] Unless otherwise stated, the reaction is carried out in 2 mL of solvent at a scale of 0.1 mmol.

[0223] Example 80: Optimization of synthetic conditions for 1,1'-bi-2'-iodo-2-phenol compounds (ligand screening)

[0224]

[0225]

[0226]

[0227] Unless otherwise specified, the reaction is carried out in 2 mL i In PrOH solvent, at a scale of 0.1 mmol

[0228] Example 81: Asymmetric ring-opening synthesis of diverse substituted 1,1'-bi-2'-iodo-2-phenol compounds from diaryliodonium salts containing different substituents

[0229]

[0230] Add CuBr (1.4 mg, 0.01 mmol) and ligand 3la (2.2 mg, 0.012 mmol) to a dry reaction tube, purge with nitrogen three times, and add 2 mL of [unspecified substance]. i Using PrOH as a solvent, the reaction tube was placed in a metal heating block at 25°C and pre-stirred for 30 min to prepare the complex. Under a nitrogen atmosphere, 9 (0.1 mmol) of the starting material cyclic diaryliodonium salt, water (0.5 mmol), and KHCO3 (0.4 mmol) were added, and the reaction was carried out at 0°C for 12 h. After the reaction was completed, the target product was obtained by column chromatography (PE). The enantiomeric excess value of the product was analyzed by high performance liquid chromatography. The experimental results of each substituent, 1'-bi-2'-iodo-2-phenol, are shown in the table below.

[0231]

[0232]

[0233] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of protection of the claims.

Claims

1. An axially chiral bipyridine ligand, characterized in that, The axially chiral bipyridine ligand is shown in the following general formula (Ⅰ): In the above formula (Ⅰ): The naphthalene portion A of the axially chiral bipyridine ligand is A-1, A-2, or A-3; the B portion of the axially chiral bipyridine ligand is a hydrogen atom or is the same as A; The axial chirality marked with * indicates either R-configuration or S-configuration; R 1 C 1-6 Any one of alkyl, alkoxy, hydroxy, phenyl, and substituted phenyl; R 2 C 1-6 Any one of alkyl, alkoxy, phenyl, or substituted phenyl; R 3 C 1-6 Any one of alkyl, alkoxy, alkylamine, phenyl, or substituted phenyl.

2. The axially chiral bipyridine ligand according to claim 1, characterized in that, When the R 1 C 1-6 When alkyl, the C 1-6 The alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when the R 1 When the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or hexoxy; when the R 1 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group. When the R 2 C 1-6 When alkyl is used, the alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when R 2 When the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or hexoxy; when the R 2 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group. When the R 3 C 1-6 When alkyl is used, the alkyl group is methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, or hexyl; when R 3 When the alkoxy group is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, or hexoxy; when the R 3 When the alkylamine group is alkylamine, the alkylamine group is dimethylamino, diethylamino, dipropylamino, diisopropylamino, di-n-butylamino, diisobutylamino, di-sec-butylamino, di-tert-butylamino, di-n-pentylamino, diisopentylamino, dineopentylamino, or dihexylamino; when the R 3 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, or a phenyl-substituted phenyl group.

3. A method for preparing the axially chiral bipyridine ligand as described in claim 1, characterized by comprising: The following steps are required: (1) Compound 3 is prepared by reacting compound 1 and compound 2 in an organic solvent under nitrogen or inert gas conditions with palladium salt, ligand and base. (2) Compound 6 is prepared by reacting compound 4 and compound 5 in an organic solvent under nitrogen or inert gas with a condensing agent. (3) Compound 7 and compound 5 are reacted in an organic solvent under nitrogen or inert gas to prepare compound 8. Y of compound 2 1 It is a chlorine atom, a bromine atom, or an iodine atom; Y 2 With Y 1 They have the same structure or are hydrogen; In compound 3, B is hydrogen or equal to A-1; Y in compound 5 3 It can be hydrogen or carboxyl. In compound 6, B is hydrogen or equal to A-2; In compound 8, B is hydrogen or equal to A-3.

4. The method for preparing the axially chiral bipyridine ligand according to claim 3, characterized in that, The organic solvents mentioned in steps (1), (2), and (3) are one or more of methanol, ethanol, isopropanol, n-butanol, acetone, dichloromethane, chloroform, carbon tetrachloride, 1,1-dichloroethane, 1,2-dichloroethane, diethyl ether, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide; The inert gas includes one or more of argon, helium, neon, and krypton; The base is selected from one of sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, cesium carbonate, potassium phosphate, sodium phosphate, sodium methoxide, potassium tert-butoxide, sodium tert-butoxide, sodium hydride, calcium hydride, n-butyllithium, sec-butyllithium, tert-butyllithium, diisopropylaminolithium, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylamine, pyridine, and 4-dimethylaminopyridine; The palladium salt includes one or more of tetratetraphenylphosphine palladium, bis(triphenylphosphine)dichloride palladium, tri-(dibenzylacetone)palladium, and palladium acetate; The ligands include one or more of triphenylphosphine, 1,1'-bis(diphenylphosphine)ferrocene, 1,3-bis(diphenylphosphine)propane, 1,4-bis(diphenylphosphine)butane, and 1,1'-binaphthyl-2,2'-bisdiphenylphosphine; The condensing reagent includes one or more of N,N'-dicyclohexylcarbodiimide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate, 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate, and N,N'-carbonyldiimidazole. In the method for preparing the axially chiral bipyridine ligand, when preparing the axially chiral ligand 3 with a chiral biaryl structure of A-1, the molar ratio of compound 1 to compound 2 is 1:1 to 3:

1. In the method for preparing the axially chiral bipyridine ligand, when preparing the axially chiral ligand 6 with a chiral biaryl structure of A-2, the molar ratio of compound 4 to compound 5 is 1:3 to 3:

1. In the preparation method of the axially chiral bipyridine ligand, when preparing the axially chiral ligand 8 with a chiral biaryl structure of A-3, the molar ratio of compound 7 to compound 5 is 1:3 to 3:

1.

5. A method for synthesizing chiral, multi-substituted 1,1'-bi-2-iodobenzene compounds, characterized in that, The method for synthesizing chiral, diversified substituted 1,1'-bi-2-iodobenzene compounds includes the following steps: complexing the axially chiral bipyridine ligand as described in claim 1 with a copper salt in an organic solvent to form a catalyst in situ; then reacting compound 9 and an iodine source at a desired reaction temperature and for a desired reaction time to obtain compound 10. Among them, R 4 -R 11 It can be hydrogen, alkyl, phenyl, substituted phenyl, carboxyl, ester, halogen, or naphthyl; The chiral axis marked with * is either S-configuration or R-configuration.

6. The method for synthesizing diverse substituted 1,1'-bi-2-iodobenzene compounds according to claim 5, characterized in that, When R 4 -R 11 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group. The organic solvent is one or more of dichloromethane, trichloromethane, 1,2-dichloroethane, diethyl ether, tetrahydrofuran, toluene, and ethyl acetate; The copper salt is selected from at least one of copper sulfate, copper chloride, copper fluoride, cuprous iodide, cuprous acetate, copper trifluoromethanesulfonate, copper tetraacetonitrile hexafluorophosphate, and cuprous thiophene-2-carboxylate. The iodine source is selected from at least one of sodium iodide, potassium iodide, lithium iodide, ammonium iodide, tetrabutylammonium iodide, and zinc iodide; The molar concentration of compound 9 in the organic solvent is 0.01–5.0 M; The molar ratio of compound 9 to the iodine source is 1:1 to 1:3; The molar ratio of the copper salt to the axially chiral bipyridine ligand is 1:5 to 1:20; The reaction temperature is -30 to 40°C; The reaction time is 1 to 180 hours.

7. A method for synthesizing chiral, multi-substituted 1,1'-bi-2'-iodo-2-thioester compounds, characterized in that, The method for synthesizing chiral, multi-substituted 1,1'-bi-2'-iodo-2-thioester compounds comprises the following steps: complexing the axially chiral bipyridine ligand as described in claim 1 with a copper salt in an organic solvent to form a catalyst in situ, followed by compound 9 and sulfur source R. 12 SK undergoes the reaction as follows at the desired reaction temperature and after the desired reaction time to obtain compound 11; Among them, R 4 -R 11 It can be hydrogen, alkyl, phenyl, substituted phenyl, carboxyl, ester, aldehyde, halogen, p-toluenesulfonyloxy, or naphthyl; R 12 It is an alkyl acyl, phenyl acyl, substituted phenyl acyl, 2-naphthyl acyl, furanyl, thiophene acyl, benzenesulfonyl, or alkylflavinyl; The chiral axis marked with * is either S-configuration or R-configuration.

8. The method for synthesizing diverse substituted 1,1'-bi-2'-iodo-2-thioester compounds according to claim 7, characterized in that, When R 4 -R 11 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group; when R 12 When R is an alkyl acyl group, the alkyl acyl group is methyl acyl, ethyl acyl, isopropyl acyl, n-butyl acyl, isobutyl acyl, tert-butyl acyl, cyclopentyl acyl, or cyclohexyl acyl; 12 When the phenyl acyl group is substituted, the substituted phenyl acyl group is a methyl-substituted phenyl acyl group, an ethyl-substituted phenyl acyl group, an isopropyl-substituted phenyl acyl group, a tert-butyl-substituted phenyl acyl group, a trifluoromethyl-substituted phenyl acyl group, a methoxy-substituted phenyl acyl group, an ethoxy-substituted phenyl acyl group, a tert-butyloxy-substituted phenyl acyl group, a fluorine-substituted phenyl acyl group, a chlorine-substituted phenyl acyl group, or a bromine-substituted phenyl acyl group; when R 12 When the alkyl flavinyl group is methyl flavinyl, ethyl flavinyl, isopropyl flavinyl, n-butyl flavinyl, isobutyl flavinyl, tert-butyl flavinyl, cyclopentyl flavinyl, or cyclohexyl flavinyl; The organic solvent is one or more of isopropanol, dichloromethane, trichloromethane, 1,2-dichloroethane, dibromomethane, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, toluene, acetonitrile, N,N-dimethylformamide, ethyl acetate, and dimethyl sulfoxide. The copper salt is selected from at least one of copper sulfate, copper acetate, cuprous acetate, copper acetylacetonate, copper fluoride, cuprous trifluoromethanesulfonate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, cuprous thiocyanate, cuprous thiophene-2-carboxylate, and copper sulfate pentahydrate. The molar concentration of compound 9 in the organic solvent is 0.01–5.0 M; The compound 9 and sulfur source R 12 The molar ratio of SK is 1:1 to 1:3; The molar ratio of the copper salt to the axially chiral bipyridine ligand is 1:5 to 1:20; The reaction temperature is -30 to 40°C; The reaction time is 1 to 180 hours.

9. A method for synthesizing chiral, multi-substituted 1,1'-bi-2'-iodo-2-phenolic compounds, characterized in that, The method for synthesizing chiral, diversified substituted 1,1'-bi-2'-iodo-2-phenol compounds comprises the following steps: complexing the axially chiral bipyridine ligand as described in claim 1 with a copper salt in an organic solvent to form a catalyst in situ, and then reacting compound 9 with water at a desired reaction temperature and for a desired reaction time to obtain compound 12; Among them, R 4 -R 11 It can be hydrogen, alkyl, phenyl, substituted phenyl, carboxyl, ester, halogen, or naphthyl; The chiral axis marked with * is either S-configuration or R-configuration.

10. The method for synthesizing diverse substituted 1,1'-bi-2'-iodo-2-phenol compounds according to claim 9, characterized in that, When R 4 -R 11 When R is an alkyl group, the alkyl group is methyl, ethyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopentyl, or cyclohexyl; 4 -R 11 When the substituted phenyl group is used, the substituted phenyl group is a methyl-substituted phenyl group, an ethyl-substituted phenyl group, an isopropyl-substituted phenyl group, a tert-butyl-substituted phenyl group, a neopentyl-substituted phenyl group, an adamantyl-substituted phenyl group, a trifluoromethyl-substituted phenyl group, a methoxy-substituted phenyl group, an ethoxy-substituted phenyl group, a tert-butyloxy-substituted phenyl group, a fluorine-substituted phenyl group, a chlorine-substituted phenyl group, or a bromine-substituted phenyl group. The organic solvent is one or more of methanol, ethanol, isopropanol, dichloromethane, chloroform, 1,2-dichloroethane, methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, toluene, and acetonitrile. The copper salt is selected from at least one of copper chloride, copper bromide, cuprous chloride, cuprous bromide, cuprous iodide, copper acetate, cuprous acetate, copper acetylacetonate, cuprous trifluoromethanesulfonate, copper tetraacetonitrile hexafluorophosphate, cuprous cyanide, and cuprous thiocyanate. The molar concentration of compound 9 in the organic solvent is 0.01–5.0 M; The molar ratio of compound 9 to water is 1:1 to 1:3; The molar ratio of the copper salt to the axially chiral bipyridine ligand is 1:5 to 1:20; The reaction temperature is -30 to 40°C; The reaction time is 1 to 180 hours.

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