N-N axial chiral monophosphine ligand as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of organic chemical synthesis, and particularly relates to an N-N axial chiral monophosphine ligand as well as a preparation method and application thereof. The structure of the N-N axial chiral monophosphine ligand is shown as a formula I and a formula II, wherein in the formula I and the formula II, Ar is aryl, substituted aryl or heteroaryl; r < 1 >-R < 3 > are respectively and independently selected from hydrogen, aryl, substituted aryl, heteroaryl, alkyl, alkylene and halogen. The N-N axial chiral monophosphine ligand is constructed by taking a phosphine-containing indole derivative and acrylate as raw materials under the action of an iridium catalyst and a chiral ligand. The ligand can be used for carbonyl reduction reaction catalyzed by rhodium and coupling reaction catalyzed by palladium, and shows excellent enantioselectivity; the conjugated structure of indole and pyrrole is combined with the electronic characteristics of phosphine groups, so that the compound is expected to be applied to the development of organic photoelectric materials and bioactive molecules. The method provides a wide space for developing a novel efficient chiral catalyst, and has a very good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, specifically relating to an NN-axis chiral monophosphine ligand, its preparation method, and its application. Background Technology

[0002] Axially chiral compounds, particularly those with biaryl skeletons, are indispensable chiral ligands and catalyst skeletons in asymmetric catalysis. Among them, N–N axially chiral compounds, as a new and important class of chiral compounds, have attracted widespread attention due to their unique structure and electronic properties in natural products, drug molecules, and dominant ligands (such as BIMIP and N,N'-diindolediphosphine). These compounds provide unique steric environments and electronic effects for asymmetric catalysis, demonstrating enormous application potential. Axially chiral biaryl monophosphines are an important class of chiral phosphine ligands. Although significant progress has been made in their asymmetric synthesis, existing synthetic methods still have the following shortcomings: For example, the cross-coupling method heavily relies on pre-constructed chiral phosphorus-substituted aryl halide precursors and has poor compatibility with substrates containing sensitive functional groups; the ring-opening strategy of cyclic phosphine salts requires specific cyclic phosphine salt starting materials, the synthetic steps are cumbersome, and the types of substrate structures are limited; although the carbene insertion method is simple, its stereoselectivity control mechanism is not yet perfect, the enantioselectivity (ee value) fluctuates greatly, and it is difficult to be universally applied to high enantioselectivity synthesis; although the transition metal-catalyzed C–P bond formation method can achieve high chirality control through kinetic resolution, this strategy has low atom economy and heavily relies on specific directing groups such as pyridine, which limits its widespread application; although the phosphine(III)-directed C–H functionalization method is an important breakthrough, its efficiency is highly dependent on the directing ability of the phosphine directing group, and its effect is sharply reduced for non-ideal substrates or molecules lacking strong coordination sites. The currently reported strategy for C–N axis chiral synthesis has an enantioselectivity of only 78% ee, and important transformations such as alkylation are difficult to achieve, indicating that its chiral induction model has inherent limitations. Summary of the Invention

[0003] The purpose of this invention is to provide an NN-axial chiral monophosphine ligand, its preparation method, and its application, thereby overcoming the shortcomings of the prior art. Starting from inexpensive raw materials, it facilitates and efficiently realizes the CH alkylation reaction of NN-axial chiral monophosphine through a short synthesis step.

[0004] To achieve the above objectives, the technical solution of the present invention is as follows: In a first aspect, the present invention provides an NN-axis chiral monophosphine ligand, the structure of which is shown in Formula I and Formula II:

[0005] In Formula I and Formula II: Ar represents aryl, substituted aryl, or heteroaryl; R1-R3 are each independently selected from the group consisting of hydrogen, aryl, substituted aryl, heteroaryl, alkyl, alkenyl, and halogen.

[0006] In some other embodiments, Ar is a five- to seven-membered nitrogen heteroaromatic group, phenyl, and phenyl substituted with at least one of C1-C5 alkyl, C2-C5 alkenyl, and halogen; R1-R3 are each independently selected from the group consisting of hydrogen, C1-C5 alkyl, C2-C5 alkenyl, a five- to seven-membered nitrogen heteroaromatic group, phenyl (abbreviated as Ph), and phenyl substituted with at least one of C1-C5 alkyl, C2-C5 alkenyl, and halogen, halogen being fluorine, chlorine, bromine, or iodine.

[0007] In some other embodiments, Ar is a five- to seven-membered nitrogen heteroaromatic group, phenyl, and phenyl substituted with at least one of C1-C5 alkyl, C2-C5 alkenyl, and halogen; R1-R3 are each independently selected from the group consisting of hydrogen, C1-C5 alkyl, C2-C5 alkenyl, a five- to seven-membered nitrogen heteroaromatic group, phenyl (abbreviated as Ph), and phenyl substituted with at least one of C1-C5 alkyl, C2-C5 alkenyl, and halogen, halogen being fluorine, chlorine, bromine, or iodine.

[0008] More specifically, the structure of the N-N axial chiral monophosphine ligand is selected from any one of the following: , ,

[0009] In a second aspect, the present application provides a method for preparing the N-N axial chiral monophosphine ligand of the first aspect, comprising the following steps: (1) reacting 2-nitrobenzaldehyde compound with carbon tetrahalide to generate 1,1-dihaloalkene compound; (2) reducing the 1,1-dihaloalkene compound with a reducing agent to generate amino compound; (4) intramolecularly cyclizing the amino compound with a base to generate indole skeleton compound; (4) performing electrophilic amination reaction on the indole skeleton compound with a base and 4-nitrobenzene-1,2-diazo-4-hydroxybenzamide to generate indole derivative skeleton compound containing amino and halogen substitution; (5) introducing pyrrole ring structure on the indole ring of the indole derivative skeleton compound under catalysis of pyridinium p-toluenesulfonate; (6) performing nucleophilic substitution reaction on the indole derivative skeleton compound containing pyrrole ring structure, metal alkyl compound, and diaryl halogenated phosphine to obtain the N-N axial chiral monophosphine ligand.

[0010] In some other embodiments, in step (1), the molar ratio of 2-nitrobenzaldehyde compound to carbon tetrahalide is 1:(1-10), the reaction temperature is -30-100 ℃, and the reaction time is 1-48 h; The carbon tetrahalide is carbon tetrachloride, carbon tetrabromide, or carbon tetraiodide. In step (2), the molar ratio of 1,1-dihaloalkene compound to reducing agent is 1:(1-20), the reaction temperature is 25-100 ℃, the reaction time is 1-48 h, and the reducing agent is iron powder or iron chloride. In step (3) or step (4), the reaction occurs in the presence of a catalyst and a base, the molar ratio of amino compound, catalyst, and base is 1:(1-10):(1-20), the reaction temperature is 25-100 ℃, the reaction time is 1-48 h, and the catalyst is a transition metal catalyst. In some other embodiments, in step (6), the molar ratio of indole skeleton compound, metal alkyl compound, and 4-nitrobenzene-1,2-diazo-4-hydroxybenzamide is 1:(1-5):(1-5), the reaction temperature is -90-100 ℃, and the reaction time is 0.5-48 h. The metal alkyl compound is one of alkyl lithium and alkyl magnesium. The diaryl halogenated phosphine is one of diaryl chlorinated phosphine, diaryl brominated phosphine, and diaryl iodinated phosphine. In steps (1)-(6), the reactions all occur in the presence of a solvent, and the solvent is independently selected from one or more of dichloromethane, ethanol, chloroform, ethyl acetate, tetrahydrofuran, methyl tetrahydrofuran, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, dioxane, toluene, xylene, benzene, and chlorobenzene.

[0011] In a third aspect, the present application provides an application of the N-N axial chiral monophosphine ligand of the first aspect in C-H alkylation reaction and palladium-catalyzed coupling reaction.

[0012] In a fourth aspect, the present application provides a method for C-H alkylation reaction, which comprises the following steps: adding alkyl acrylate, [Ir(coe)Cl]2, and ligand L7 into a solvent, stirring at room temperature, adding the N-N axial chiral monophosphine ligand of the first aspect as a substrate, performing alkylation reaction, cooling to room temperature after the reaction is completed, adding an oxidizing agent to perform oxidation reaction, and obtaining the product after removing the solvent and purification.

[0013] In some other embodiments, the molar ratio of alkyl acrylate to N-N axial chiral monophosphine ligand is 3:(1-2). The structural formula of ligand L7 is as follows: Ligand L7 is a chiral ligand with a spirocyclic structure, wherein the solid and dashed lines in the structural formula represent the distance.

[0014] The structural formula of the alkyl acrylate is as follows: , wherein R is selected from hydrogen, C1-C5 alkyl, C2-C5 alkenyl, five- to seven-membered nitrogen heterocyclic aryl, phenyl, and phenyl substituted with at least one of C1-C5 alkyl, C2-C5 alkenyl, and halogen; The temperature of the alkylation reaction is 140-160°C, and the reaction time is 1-3 h. The time of the oxidation reaction is 0.5-1 h.

[0015] In a fifth aspect, the present application provides a method for palladium-catalyzed coupling reaction, which uses the N-N axis chiral monophosphine ligand of the first aspect as the ligand of the palladium catalyst to catalyze the coupling reaction of acetate and indole derivative; The structural formula of the acetate is as follows: , wherein Ar1 or Ar2 is independently selected from one of aryl, substituted aryl, and heteroaryl; The structural formula of the indole derivative is as follows: , wherein R is selected from one of hydrogen, aliphatic substituent, alkyl, alkenyl, alkynyl, and aryl.

[0016] The beneficial effects of the present application are as follows: The present application provides a process for constructing N-N axis chiral monophosphine ligand by using indole derivative containing phosphine and acrylate as raw materials, under the action of iridium catalyst and chiral ligand, realizing enantioselective alkylation, developing high-efficiency kinetic resolution process for indole-indole skeleton, and realizing high selectivity factor. The ligand can be used for rhodium-catalyzed carbonyl reduction reaction and palladium-catalyzed coupling reaction, and exhibits excellent enantioselectivity; the conjugated structure of indole and pyrrole combined with the electronic properties of phosphine group is expected to be applied in the development of organic optoelectronic materials (such as OLEDs) and biologically active molecules. The modular synthesis strategy can derive diversified structures, providing a broad space for the development of new efficient chiral catalysts, and has very good application prospect. DETAILED DESCRIPTION

[0017] Those skilled in the art will understand that the following examples are only used to illustrate the present application, and should not be regarded as limiting the scope of the present application. The specific conditions are not specified in the examples, and are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The components used are not specified by the manufacturer, and are all conventional products that can be obtained by market purchase.

[0018] Firstly, the examples provide an N-N axis chiral monophosphine ligand, the structure of which is shown in formula I and formula II:

[0019] Formula I, Formula II: Ar is aryl, substituted aryl, heteroaryl; R1-R3 are each independently selected from one of hydrogen, aryl, substituted aryl, heteroaryl, alkyl, alkenyl and halogen.

[0020] Secondly, the embodiment provides a synthesis method of N-N axial chiral monophosphine ligand, comprising the following steps: (1) 2-nitrobenzaldehyde compound reacts with carbon tetrahalide to generate 1,1-dihaloalkene compound (marked as 2), introducing dihaloalkene structure; (2) 1,1-dihaloalkene compound reduces nitro compound to amino compound (marked as 3) under a reduction system; (3) under the catalysis of transition metal, intramolecular cyclization of amino compound generates indole skeleton; (4) through potassium tert-butoxide catalyzed nucleophilic reaction, indole ring amino skeleton is converted into indole derivative skeleton containing amino and halogen substitution; (5) under the catalysis of pyridinium p-toluenesulfonate, pyrrole ring structure is introduced on the indole ring; (6) using the deprotonation of alkyl metal, nucleophilic intermediate is generated, and nucleophilic substitution reaction is generated with diaryl chlorophosphine, and diphenyl phosphine group is introduced in the molecule.

[0021] More specifically, the synthesis route and parameters are as follows: Step (1): the molar ratio of 2-nitrobenzaldehyde compound and carbon tetrahalide is 1:1-10; the reaction temperature is-30-100 ℃; the reaction time is 1-48 h; the carbon tetrahalide used is carbon tetrachloride, carbon tetrabromide, carbon tetraiodide; the triaryl phosphine used is triphenyl phosphine. The specific reaction route is as follows:

[0022] Step (2): the molar ratio of compound 2 and reducing agent is 1:1-20; the reaction temperature is 25-100 ℃; the reaction time is 1-48 h; the reducing agent used in the reaction is iron powder, iron chloride. The specific reaction route is as follows:

[0023] Step (3): the molar ratio of compound 3, catalyst and base is 1:1-10:1-20; the reaction temperature is 25-100 ℃; the reaction time is 1-48 h. The specific reaction route is as follows:

[0024] Step (4): the molar ratio of compound 4 to catalyst to base is 1:1-10:1-20; the reaction temperature is 25-100 ℃; and the reaction time is 1-48 h. The specific reaction route is as follows:

[0025] Step (5): the molar ratio of compound 5 to pyridine p-toluenesulfonic acid salt (PPTS) is 1:1-10:1-20; the reaction temperature is 25-100 ℃; and the reaction time is 1-48 h. The specific reaction route is as follows:

[0026] Step (6): the ratio of compound 5 to metal alkyl compound to diaryl halogenated phosphine is 1:1-5:1-5; the reaction temperature is -90-100 ℃; and the reaction time is 0.5-48 h. The metal alkyl compound is alkyl lithium or alkyl magnesium; and the diaryl halogenated phosphine is diaryl chlorinated phosphine, diaryl brominated phosphine or diaryl iodinated phosphine. The specific reaction route is as follows:

[0027] The organic solvent used in steps (1)-(6) is dichloromethane, chloroform, ethyl acetate, tetrahydrofuran, methyl tetrahydrofuran, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, dioxane, toluene, xylene, benzene, chlorobenzene, any one or any mixture thereof; Ar is aryl, substituted aryl or heteroaryl; R1-R3 are each independently selected from hydrogen, aryl, substituted aryl, heteroaryl, alkyl, olefinic group and halogen.

[0028] Next, the examples provide a corresponding selective C-H alkylation reaction of transition metal-catalyzed N-N axis chiral monophosphine ligand, including the following steps: (1) the N-N axis chiral monophosphine ligand (as a substrate) is reacted with an alkyl acrylate in the presence of an iridium catalyst and a ligand (L*, i.e., L7) to generate a target intermediate; (2) the target intermediate is subjected to an oxidation reaction with an oxidizing agent to oxidize the phosphine in the reaction, thereby obtaining a monoalkylated product.

[0029]

[0030] wherein the ratio of the N-N axial chiral monophosphine ligand to the iridium catalyst to the ligand is 1: (0.005-2): (0.01-4), the reaction temperature is 100-150℃, the reaction time is 3-24 h, the alkyl acrylate used includes one or more of methyl acrylate, ethyl acrylate, n-butyl acrylate, n-dodecyl acrylate and branched alkyl acrylate, the organic solvent used is one or more of dichloromethane, chloroform, ethyl acetate, tetrahydrofuran, methyl tetrahydrofuran, diethyl ether, dibutyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, dioxane, toluene, xylene, benzene and chlorobenzene, the oxidant used is one or more of hydrogen peroxide, meta-chloroperoxybenzoic acid and tert-butyl hydroperoxide, and the iridium catalyst is one or more of [Ir(cod)Cl]2, Ir(cod)SbF6, Ir(cod)BF4, Ir(cod)NTf2, Ir(C2H4)Cl, Ir(C2H4)SbF6, Ir(C2H4)BF4 and Ir(C2H4)NTf2.

[0031] Then, the embodiment provides the use of the N-N axial chiral monophosphine ligand as a ligand of a palladium catalyst to catalyze the coupling reaction of acetic acid ester and indole derivative, and the reaction formula is specifically shown in the following formula (1):

[0032] wherein R is one of hydrogen, alkyl, alkenyl, alkynyl and aryl; Ar1 or Ar2 is independently selected from one of aryl, substituted aryl and heteroaryl. The palladium catalyst is one or more of Pd(OAc)2, PdCl2, Pd(TFA)2, Pd(PPh3)2Cl2, Pd(CH3CN)2Cl2, CNPd(py)2Cl2, Pd(cod)Cl2 and Pd(CH3CN) 42 .

[0033] The scheme of the present application is described below in combination with specific embodiments: Embodiment 1 The embodiment provides 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole and a synthesis method thereof, which comprises the following steps: (1) The synthesis route of 2-(2,2-dibromoethenyl) aniline is as follows:

[0034] To a flask containing 2-nitrobenzaldehyde (1.51 g, 10 mmol) and carbon tetrabromide (CBr4, 4.97 g, 15 mmol) in dichloromethane (DCM, 50 mL) was added a solution of triphenylphosphine (PPh3, 7.86 g, 30 mmol) in dichloromethane (15 mL) dropwise at 0 °C. After the addition was complete, the reaction mixture was stirred for an additional 0.5 h, then allowed to warm to room temperature and stirred for another 0.5 h. Ethyl ether (50 mL) was then added, the mixture was filtered through a short pad of silica gel (or celite), and the filter cake was washed with ethyl ether (10 mL). The filtrates were combined and concentrated under reduced pressure. To the residue was added ethanol (40 mL), acetic acid (10 mL), iron powder (8 g, 142 mmol), and ferric chloride (FeCl3, 200 mg, 1.2 mmol), and the resulting suspension was placed in an oil bath preheated to 100 °C and stirred for 4 h. After the reaction was complete as monitored by TLC, it was cooled to room temperature, filtered through a Buchner funnel, and the filtrate was extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether: ethyl acetate = 10: 1) to give the product 2-(2,2-dibromoethenyl)aniline.

[0035] (2) The synthetic route of 2-bromoindole is as follows:

[0036] To a reaction tube equipped with a magnetic stir bar was added 2-(2,2-dibromoethenyl)aniline (1 mmol), palladium acetate (Pd(OAc)2, 0.05 mmol, 5 mol%), tri-tert-butylphosphine tetrafluoroborate (P(t-Bu)3·HBF4, 17.4 mg, 6 mol%), and potassium carbonate (K2CO3, 2 mmol) sequentially. The reaction tube was purged with nitrogen three times, toluene (3 mL) was added, and the mixture was sealed. The mixture was stirred at room temperature for 5 min, then placed in an oil bath preheated to 100 °C and stirred for another 14 h. After the reaction was complete, it was cooled to room temperature, quenched with water, and extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 10: 1) to give 2-bromoindole.

[0037] (3) The synthetic route of 2-bromo-1H-indol-1-amine is as follows:

[0038] To a solution of compound 2-bromo-lH-indole-l-carboxylic acid (5 mmol, 1 eq) in DMF (20 mL) was added HATU (6 mmol, 1.2 eq) and DIPEA (6 mmol, 1.2 eq) followed by the addition of amine (5 mmol, 1 eq). The reaction mixture was stirred at room temperature for 12 h. The reaction was monitored by TLC. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: pet ether / ethyl acetate = 10:1) to give the product 2-bromo-l-(lH-pyrrol-l-yl)-lH-indole in 75% yield.

[0039] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.53 - 7.42 (m, 2H), 7.28 - 7.20 (m, 1H), 7.14 - 7.06 (m, 1H), 6.54 - 6.54 (m, 1H), 4.58 (s, 2H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 137.1, 125.5, 122.2, 120.3, 119.6, 115.2, 109.4, 102.1. High resolution mass spectrum: (ESI) m / z: [M+H] + Theoretical value C8H8BrN2 + 210.9865; Found 210.9862.

[0040] (4) The synthesis route of 2-bromo-l-(lH-pyrrol-l-yl)-lH-indole is as follows:

[0041] To a mixture of compound 2-bromo-lH-indole-l-carboxylic acid (5 mmol, 1 eq), 2,5-dimethoxytetrahydrofuran (7.5 mmol, 1.5 eq) and pyridine p-toluenesulfonic acid salt (PPTS, 1 mmol, 20 mol%) was added toluene (20 mL) followed by placing in an 80 °C oil bath for 10 h. After completion of the reaction, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel (eluent: pet ether / ethyl acetate = 50:1) to give the product 2-bromo-l-(lH-pyrrol-l-yl)-lH-indole in 75% yield.

[0042] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.59 - 7.55 (m, 1H), 7.23 - 7.17 (m, 2H), 7.00 - 6.97 (m, 1H), 6.88 - 6.81 (m, 2H), 6.69 - 6.65 (m, 1H), 6.38 - 6.34 (m, 2H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 137.7, 125.8, 123.4, 122.1, 121.7, 120.0, 114.1, 108.9, 108.3, 104.4. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 12 H 10 BrN2 + 261.0022; Found 261.0019.

[0043] (5) The synthesis route of 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole is as follows:

[0044] To compound 2-bromo-1-(1H-pyrrol-1-yl)-1H-indole (5 mmol, 1.0 eq) dissolved in anhydrous tetrahydrofuran (THF, 10 mL) was slowly added n-butyllithium (n-BuLi, 4.4 mL, 7 mmol) dropwise at -78 °C under nitrogen protection. After stirring for 20 minutes, chlorodiarylphosphine (1.35 mL, 7.5 mmol) was added, and the reaction mixture was raised to room temperature and continued to stir for 12 h. The reaction was quenched with water, and the organic phase was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 20:1) to obtain the product 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole with a yield of 70%.

[0045] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.59 - 7.53 (m, 1H), 7.41 - 7.34 (m, 10H), 7.24 - 7.19 (m, 1H), 7.19 - 7.14 (m, 1H), 6.99 - 6.94 (m, 1H), 6.62 - 6.57 (m, 2H), 6.24 (d, J = 0.9 Hz, 1H), 6.18 (t, J = 2.3 Hz, 2H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 140.0, 139.34, 139.29, 134.9, 134.8, 133.8, 133.7, 133.1, 133.0, 132.7, 132.6, 129.2, 128.6, 128.5, 125.7, 123.6, 122.3, 121.1, 120.7, 109.9, 108.8, 107.7. Phosphine spectrum nuclear magnetic (243 MHz, CDC13) δ -30.60. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 24 H 20 N2P + 367.1359; Found 367.1350.

[0046] Example 2 This example provides 2-(diphenylphosphino)-1-(2-methyl-1H-pyrrol-1-yl)-1H- indole and a method for synthesizing the same, which is different from Example 1 in that the synthesis of Step (4) and Step (5) is different, and the other steps are consistent with Example 1.

[0047] Specifically, the synthesis route of 2-bromo-1-(2-methyl-1H-pyrrol-1-yl)-1H- indole in Step (4) is as follows:

[0048] To a mixture of compound 2-bromo-1H-indole-1-amine (5 mmol, 1 equivalent), 4-pentanone aldehyde (7.5 mmol, 1.5 equivalents) and pyridine p-toluenesulfonic acid salt (PPTS, 1 mmol, 20 mol%) was added toluene (20 mL), then placed in an 80°C oil bath for 10 h. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 20:1) to obtain the product 2-bromo-1-(2-methyl-1H-pyrrol-1-yl)-1H-indole with a yield of 35%.

[0049] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.6 - 7.5 (m, 1H), 7.2 - 7.1 (m, 2H), 7.0-6.9 (m, 1H), 6.8 - 6.7 (m, 1H), 6.7 - 6.7 (m, 1H), 6.2 (t, J = 3.5 Hz, 1H), 6.1 - 6.0 (m, 1H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 137.3, 130.5, 125.9, 123.4, 121.6, 120.7, 120.1, 114.2, 109.0, 107.3, 105.8, 104.3, 100.2, 10.4. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 13 H 12 BrN2 + 275.0178; Found 275.0172. The synthetic route of 2-(diphenylphosphino)-1-(2-methyl-1H-pyrrol-1-yl)-1H-indole in Step (5) is as follows:

[0050] To compound 2-bromo-1-(2-methyl-1H-pyrrol-1-yl)-1H-indole (5 mmol, 1.0 eq) dissolved in anhydrous tetrahydrofuran (THF, 10 mL) was added dropwise n-butyllithium (n-BuLi, 4.4 mL, 7 mmol) slowly at -78 °C under nitrogen protection. After stirring for 20 minutes, chlorodiphenylphosphine (1.35 mL, 7.5 mmol) was added, and the reaction mixture was raised to room temperature and continued to stir for 12 h. The reaction was quenched with water, and the organic phase was extracted with ethyl acetate three times. The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 20:1) to give 2-(diphenylphosphino)-1-(2-methyl-1H-pyrrol-1-yl)-1H-indole in a yield of 65%.

[0051] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.57 - 7.53 (m, 1H), 7.43 - 7.32 (m, 10H), 7.23 - 7.19 (m, 1H), 7.17 - 7.13 (m, 1H), 6.90 (dd, J = 8.2, 1.1 Hz, 1H), 6.36 (t, J = 2.5 Hz, 1H), 6.29 (d, J = 0.9 Hz, 1H), 6.03 (t, J = 3.4 Hz, 1H), 5.98 - 5.93 (m, 1H), 1.78 (s, 3H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 139.6, 139.3 (d, J = 7.2 Hz), 134.8, 134.7, 133.9, 133.82, 133.81, 133.7, 130.2, 129.2, 129.19, 128.51, 128.5, 128.5, 128.4, 125.9, 123.7, 121.14, 121.1, 120.8, 110.0, 109.0, 106.7, 105.4, 10.5. Phosphine spectrum nuclear magnetic (243 MHz, CDC13) δ -30.19. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 24 H 19 FN2P + 381.1515; Found 385.1505.

[0052] Example 3 This example provides 2-(diphenylphosphino)-1,1'-biindole and a method of synthesizing the same, comprising the following steps: (1) The synthesis route of 2-((1H-indol-1-yl)amino)benzaldehyde is as follows:

[0053] Into a 500 mL reaction flask, 2-nitrobenzyl alcohol (20 mmol), indoline (10 mmol, 1.0 equiv), tetraethylammonium iodide (TEAI, 2.57 g, 10 mmol), acetic acid (0.57 mL, 10 mmol) and dichloromethane (DCM, 200 mL, 0.05 M) were added successively under air atmosphere. The reaction mixture was stirred under UV light (385-405 nm) at room temperature for 24 h. After the reaction was completed, the solvent was removed by concentration under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 50:1) to obtain the product 2-((1H-indol-1-yl)amino)benzaldehyde in 83% yield.

[0054] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 10.35 (s, 1H), 10.00 (s, 1H), 7.65 (d, J = 4.3 Hz, 2H), 7.26 (s, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.16 (t, J = 3.0 Hz, 2H), 6.91 (s, 1H), 6.58 (s, 1H), 6.08 (d, J = 8.5 Hz, 1H). Carbon spectrum nuclear magnetic (100 MHz, CDC13) δ 194.4, 150.3, 136.2, 135.6, 135.5, 128.3, 126.6, 122.7, 121.1, 120.6, 118.94, 118.90, 111.8, 109.1, 101.5. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 15 H 13 N2O + 237.1022; Found 237.1029.

[0055] (2) The synthetic route of N-(2-(2,2-dibromoethenyl)phenyl)-1H-indol-1-amine is as follows:

[0056] To a mixture of carbon tetrabromide (6.63 g, 20 mmol) and zinc powder (5.20 g, 80 mmol) and anhydrous DCM (80 mL) was added a solution of triphenylphosphine (5.25 g, 20 mmol) in DCM (20 mL) under nitrogen atmosphere. After 30 min, 2-((1H-indol-2-yl)amino)benzaldehyde (10 mmol) was added and the reaction mixture was stirred at 0 °C for 12 h. After completion of the reaction, the mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 50:1) to give N-(2-(2,2-dibromoethenyl)phenyl)-1H-indol-1-amine in 65% yield.

[0057] Hydrogen spectrum nuclear magnetic (400MHz, CDCl3): δ 7.57 (d, J = 7.4 Hz, 1H), 7.40 (s, 1H), 7.24 (d, J = 7.7 Hz, 1H), 7.16 (d, J = 7.2 Hz, 1H), 7.11 (s, 1H), 7.09 (s, 1H), 7.08 - 7.05 (m, 1H), 7.00 (t, J = 7.9 Hz, 1H), 6.83 (t, J = 7.5 Hz, 1H), 6.53 (s, 1H), 6.48 (s, 1H), 6.00 (d, J = 8.2 Hz, 1H). Carbon spectrum nuclear magnetic (400MHz, CDCl3): (100 MHz, CDCl3) δ 144.0, 135.7, 133.12, 129.9, 129.1, 128.5, 126.6, 122.6, 121.2, 121.2, 120.8, 120.5, 112.5, 109.3, 101.2, 94.8. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 16 H 13 N2Br2 + 390.9440; Found 390.9445.

[0058] (3) The synthesis route of 2-bromo-1,1'-biindoline is as follows:

[0059] To a solution of N-(2-(2,2-dibromoethenyl)phenyl)-1H-indol-1-amine (5 mmol, 1.0 eq) in anhydrous toluene (10 mL) was added CuI (190.5 mg, 1.0 mmol), rac-BINOL (572.6 mg, 2 mmol) and K2CO3(1.38 g, 10 mmol) under nitrogen atmosphere. The mixture was stirred at 100 °C for 12 h. After the reaction was checked to be complete, the solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 200:1) to give 2-bromo-1,1'-biindoline in 90% yield.

[0060] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.63 (d, J = 7.6 Hz, 1H), 7.53 (d, J = 7.8 Hz, 1H), 7.15 (t, J = 5.6 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 7.06 (d, J = 7.8 Hz, 1H), 6.74 (t, J = 7.6 Hz, 2H), 6.67 (s, 1H), 6.63 (d, J = 3.4 Hz, 1H). Carbon spectrum nuclear magnetic (100 MHz, CDC13) δ 137.4, 136.6, 128.1, 126.4, 126.2, 123.5, 121.9, 121.4, 121.4, 120.2, 114.4, 109.1, 109.0, 104.9, 102.8. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 16 H 12 N2Br + 311.0178; calculated 311.0177.

[0061] (4) The synthesis route of 2-(diphenylphosphino)-1,1'-biindoline is as follows:

[0062] Under a nitrogen atmosphere at -78 °C, n-butyllithium (4.4 mL, 7 mmol) was slowly added to a mixture of 2-bromo-1,1'-diindole (5 mmol, 1.0 equivalent) and anhydrous THF (10 mL). After 20 minutes, diphenylphosphine chloride (1.35 mL, 7.5 mmol) was added, and the mixture was stirred at room temperature for 12 h. After the reaction was monitored for completion, the reaction was quenched with water and extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated. The crude residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 200:1) to give 2-(diphenylphosphino)-1,1'-diindole in 90% yield.

[0063] 1H NMR (400 MHz, CDCl3) δ 7.51 (t, J = 9.6 Hz, 2H), 7.28 (s, 2H), 7.26 (s, 2H), 7.23 (s, 2H), 7.22 (s, 1H), 7.20 (d, J = 4.9 Hz, 2H), 7.16 (s, 1H), 7.04 (dd, J = 12.3, 7.2 Hz, 3H), 6.94 (d, J = 8.1 Hz, 1H), 6.79 (s, 1H), 6.64 (d, J = 8.2 Hz, 1H), 6.57 (d, J = 8.3 Hz, 1H), 6.41 (s, 1H), 6.28 (s, 1H). Carbon NMR (100 MHz, CDCl3) δ 140.0, 139.9, 139.6, 136.6, 135.0, 134.9, 134.6, 134.5, 133.9, 133.9, 133.7, 133.7, 129.2, 129.1, 128.6, 128.5, 128.5, 128.4, 128.4, 126.2, 126.1, 123.6, 122.9, 121.3, 121.0, 121.0, 120.9, 110.3, 109.4, 109.0, 102.2. Phosphine NMR (162 MHz, CDCl3) δ -30.66. High-resolution mass spectrometry: (ESI) m / z: [M+H] + Calculated value C 28 H 22 N2P + 417.1515; Calculated value 417.1523.

[0064] Example 4 This embodiment provides the following route for the enantioselective CH alkylation reaction of iridium-catalyzed NNN-axial chiral phosphine:

[0065] In which 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole prepared in Example 1 was used as the substrate, and the specific reaction process was as follows: Ethyl acrylate was replaced by alkyl acrylate (0.3 mmol, 3.0 eq), [Ir(coe)Cl]2(chloro bis(cyclooctene) iridium(I) dimer, 4.5 mg, 0.005 mmol, 5 mol%), ligand L7 (3.3 mg, 0.01 mmol, 10 mol%), followed by the addition of toluene (0.5 mL), and stirring at room temperature for 2 h. Then 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole (0.1 mmol, 1.0 eq) dissolved in toluene (0.5 mL) was added, and the reaction mixture was stirred at 150 °C for 4.5 h. After the reaction was completed, it was cooled to room temperature, and H2O2 was added to continue the reaction for 0.5 h. After the reaction was completed, the solvent was removed under reduced pressure, and the crude product was directly purified by column chromatography to obtain the target product, which was separated by preparative chiral high-performance liquid chromatography. The results were as follows: (if H2O2 is not added, the corresponding monophosphine ligand can be directly obtained)

[0066] The target compound was characterized as follows: (1) Compound 3a, (S)-3-(1-(2-(diphenylphosphoryl)-1H-indol-1-yl)-1H-pyrrol-2-yl)propionic acid ester. Synthesized by the general method, and the crude product was separated by high-performance liquid chromatography (AD-H, isopropanol / n-hexane = 30 / 70, flow rate = 0.6 mL / min, l = 254 nm) t R = 22.7 min (major), 24.6 min (minor), yield 68%.

[0067] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.82 - 7.73 (m, 2H), 7.73 - 7.61 (m, 3H), 7.60 - 7.49 (m, 2H), 7.51 - 7.40 (m, 4H), 7.28 (dd, J = 14.0, 6.3 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H), 6.81 - 6.71 (m, 2H), 6.22 (s, 1H), 5.90 (t, J = 3.6 Hz, 1H), 5.79 (d, J = 3.9 Hz, 1H), 4.18 - 3.83 (m, 2H), 2.71 - 2.14 (m, 4H), 1.19 (t, J = 7.1 Hz, 3H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 172.6, 140.7 (d, J = 5.4 Hz), 133.5, 132.30 (d, J = 117.2 Hz), 132.27 (d, J = 2.7 Hz), 132.19 (d, J = 2.9 Hz), 132.0, 131.91, 131.89, 131.81, 131.79, 130.9, 130.8 (d, J = 111.2 Hz), 128.5, 128.4, 126.1, 124.3, 124.2, 122.1, 122.0, 121.3, 114.9, 114.8, 109.5, 106.9, 104.3, 60.2, 32.3, 19.9, 14.1. Phosphine spectrum nuclear magnetic (162 MHz, CDC13) δ 15.32. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 29 H 28 N2O3P + 483.1832; Found 483.1822. [a]D25= -1505° (c = 0.28, CH2Cl2, 92% ee).

[0068] (2) Compound 3b, (S)-methyl 3-[l-(2-diphenylphosphinoyl-lH-indol-l-yl)-lH-pyrrol-2-yl]propanoate. Synthesized by the general method, the crude product was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 3: 1) to give a brown oil in 69% yield.

[0069] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.84 - 7.74 (m, 2H), 7.73 - 7.61 (m, 3H), 7.60 - 7.51 (m, 2H), 7.51 - 7.39 (m, 4H), 7.35- 7.25 (m, 1H), 7.23 - 7.17 (m, 1H), 6.82 - 6.72 (m, 2H), 6.21 (dd, J = 3.2, 1.8 Hz, 1H), 5.89 (t, J = 3.5 Hz, 1H), 5.8 - 5.7 (m, 1H), 3.59 (s, 3H), 2.46 - 2.24 (m, 4H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 173.1, 140.7 (d, J = 5.5 Hz), 133.4, 132.3 (d, J = 117.3 Hz), 132.23 (d, J = 2.7 Hz), 132.15 (d, J = 2.8 Hz), 131.94, 131.91, 131.8, 130.84, 130.76 (d, J = 111.2 Hz) 128.5, 128.4, 126.1, 124.3, 124.2, 122.2, 122.1, 121.3, 114.9, 114.8, 109.5, 107.0, 104.3, 51.5, 32.1, 19.8. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.27. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 28 H 26 N2O3P + 469.1676; Found 469.1667.[α] D 25 = -1108° (c = 0.17, CH2Cl2, 96% ee). High performance liquid chromatography separation conditions (AD-H, isopropanol / n-hexane = 20 / 80, flow rate = 0.6 mL / min, l = 254 nm) t R = 17.6 min (major), 19.3 min (minor).

[0070] (3) Compound 3c, (S)-3-[1-(2-diphenylphosphinoyl-1H-indol-1-yl)-1H-pyrrol-2- yl]propionic acid butyl ester. Synthesized by the general method, the crude product was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 3:1) to give 3c as a brown oil in 57% yield.

[0071] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.81 - 7.73 (m, 2H), 7.72 - 7.60 (m, 3H), 7.60 - 7.51 (m, 2H), 7.51 - 7.37 (m, 4H), 7.34 - 7.27 (m, 1H), 7.25 - 7.17 (m, 1H), 6.79 - 6.69 (m, 2H), 6.23 - 6.20 (m, 1H), 5.90 (t, J = 3.5 Hz, 1H), 5.80 - 5.75 (m, 1H), 3.99 (t, J = 6.8 Hz, 2H), 2.53 - 2.10 (m, 4H), 1.72 - 1.44 (m, 2H), 1.42 - 1.03 (m, 2H), 0.90 (t, J = 7.4 Hz, 3H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 172.8, 140.7 (d, J = 5.5 Hz), 133.5, 132.29 (d, J = 117.2 Hz), 132.26 (d, J = 2.7 Hz), 132.18 (d, J = 2.7 Hz), 132.98, 131.95, 131.88, 131.85, 130.9, 130.8 (d, J = 111.3 Hz), 128.6, 128.4, 126.2, 124.4, 124.2, 122.2, 122.1, 121.3, 115.0, 114.8, 109.6, 107.0, 104.4, 64.2, 32.4, 30.6, 20.0, 19.1, 13.7. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.36. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 31 H 32 N2O3P + 511.2145; Found 511.2135.[α] D 25= -525° (c = 0.17, CH2Cl2, 94% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 15 / 85, flow rate = 0.6 mL / min, l = 254 nm) t R = 22.6 min (major), 24.8 min (minor).

[0072] (4) Compound 3d, (S)-3-[l-(2-diphenylphosphinoyl-lH-indol-l-yl)-lH-pyrrol-2- yl]propionic acid dodecyl ester. Synthesized by the general method, the crude product was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 3: 1) to give 3d as a brown oil in 62% yield.

[0073] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.83 - 7.72 (m, 2H), 7.72 - 7.61 (m, 3H), 7.60 - 7.51 (m, 2H), 7.55 - 7.39 (m, 4H), 7.33 - 7.26 (m, 1H), 7.24 - 7.16 (m, 2H), 6.81 - 6.72 (m, 1H), 6.25 - 6.19 (m, 1H), 5.93 - 5.87 (m, 1H), 5.81 - 5.76 (m, 1H), 3.97 (t, J = 6.8 Hz, 2H), 2.45 - 2.16 (m, 4H), 1.59 - 1.51 (m, 2H), 1.28 - 1.23 (m, 18H), 0.88 (t, J = 6.8 Hz, 3H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 172.7, 140.7 (d, J = 5.5 Hz), 133.5, 132.23 (d, J = 117.3 Hz), 132.21 (d, J = 2.7 Hz), 132.1 (d, J = 2.7 Hz), 131.93, 131.91, 131.83, 131.80, 130.84, 130.77 (d, J = 111.2 Hz), 128.5, 128.4, 126.1, 124.3, 124.2, 122.2, 122.0, 121.3, 114.9, 114.8, 109.5, 106.9, 104.3, 64.5, 32.3, 31.9, 29.6, 29.59, 29.55, 29.49, 29.3, 29.2, 28.5, 25.9, 22.7, 19.9, 14.1. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.25.

[0074] High resolution mass spectrum: (ESI) m / z: [M+H] + Theoretical value C39H 48 O3P + 623.3397; Found 623.3395. [a] D 25 = -500° (c = 0.1, CH2Cl2, 97% ee). High performance liquid chromatography separation condition (IA-H, isopropanol / n-hexane = 5 / 95, flow rate = 0.6 mL / min, l = 254 nm) tR = 50.2 min (major), 54.9 min(minor).

[0075] (5) Compound 3e, 3-[l-((S)-2-diphenylphosphinoyl-lH-indol-l-yl)-lH-pyrrol-2- yl]propionic acid 2-ethylhexyl ester. Synthesized by the general method, the crude product was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 3: 1) to give 3e as a brown oil in 60% yield.

[0076] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.84 - 7.72 (m, 2H), 7.71 - 7.60 (m, 3H), 7.59 - 7.51 (m, 2H), 7.51 - 7.39 (m, 4H), 7.32 - 7.25 (m, 1H), 7.20 (t, J = 7.4 Hz, 1H), 6.85 - 6.70 (m, 2H), 6.23 (dd, J = 3.1, 1.8 Hz, 1H), 5.90 (t, J = 3.5 Hz, 1H), 5.78 (dd, J = 4.1, 1.7 Hz, 1H), 3.94 - 3.85 (m, 2H), 2.43 - 2.20 (m, 4H), 1.29 - 1.21 (m, 9H), 0.89 - 0.83 (m, 6H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 172.8, 140.7 (d, J = 5.6 Hz), 133.5, 132.23 (d, J = 117.3 Hz), 132.21 (d, J = 2.8 Hz), 132.1 (d, J = 3.0 Hz), 131.94, 131.90, 131.84, 131.80, 130.85, 130.77 (d, J = 111.2 Hz), 128.5, 128.38, 128.37, 126.1, 124.3, 124.2, 122.2, 122.0, 121.3, 114.9, 114.8, 109.5, 106.9, 104.3, 66.7, 38.6, 32.3, 30.3, 28.8, 23.7, 22.9, 19.9, 14.0, 10.9. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.26. High resolution mass spectrum: (ESI) m / z: [M+H] + Theoretical value C 35 H40 N2O3P + 567.2771; Found 567.2759.[α] D 25 = -787.5° (c = 0.23, CH2Cl2, 91% ee). HPLC separation conditions (OD-H, isopropanol / n-hexane = 5 / 95, flow rate = 0.8 mL / min, l = 254 nm) t R = 20.8 min (minor),27.6 min (major).

[0077] (6) Compound 3f, (S)-3-[l-(2-diphenylphosphinyl-lH-indol-l-yl)-lH-pyrrol-2- yl]propionic acid 2-phenoxyethyl ester. Synthesized by the general method, the crude product was purified by column chromatography (silica gel, petroleum ether: ethyl acetate = 3: 1) to give 3f as brown oil in 60% yield.

[0078] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.80 - 7.72 (m, 2H), 7.71 - 7.61 (m, 3H), 7.58 - 7.50 (m, 2H), 7.49 - 7.38 (m, 4H), 7.33 - 7.25 (m, 3.5H), 7.24 - 7.16 (m, 1H), 6.99 - 6.93 (m, 1H), 6.92 - 6.84 (m, 2H), 6.81 - 6.76 (m, 1H), 6.74 (d, J = 4.4 Hz, 1H), 6.25 - 6.19 (m, 1H), 5.88 (t, J = 3.5 Hz, 1H), 5.82 - 5.77 (m, 1H), 4.39 - 4.32 (m, 2H), 4.17 - 4.07 (m, 2H), 2.54 - 2.17 (m, 4H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 172.6, 158.4, 140.7 (d, J = 5.4 Hz), 133.3, 132.6, 132.3 (d, J = 2.1 Hz), 132.2 (d, J = 2.8 Hz), 131.91, 131.89, 131.84, 131.83, 131.6, 130.9, 130.7 (d, J = 111.0 Hz), 129.5, 128.5, 128.4, 126.2, 124.3, 124.2, 122.2, 122.1, 121.4, 121.1, 114.94, 114.85, 114.5, 109.5, 107.0, 104.4, 65.7, 62.7, 32.1, 19.8. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.24. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 35 H 32 N2O3P + 575.2094; Found 575.2090.[α] D 25 = 140° (c = 0.14, CH2Cl2, 93% ee). High performance liquid chromatography separation conditions (AD-H, isopropanol / n-hexane = 30 / 70, flow rate = 0.7 mL / min, l = 254 nm) t R= 19.4 min (major), 27.2 min (minor).

[0079] (7) Compound 3g, (S)-3-(1-(2-(diphenylphosphoryl)-1H-indol-1-yl)-1H-pyrrol-2- yl)benzyl propanoate. Refer to the general procedure for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3:1, volume ratio) to give 3g as brown oil in 52% yield.

[0080] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.83 - 7.75 (m, 2H), 7.74 - 7.62 (m, 3H), 7.60 - 7.52 (m, 2H), 7.51 - 7.41 (m, 4H), 7.41 - 7.33 (m, 3H), 7.33 - 7.27 (m, 3H), 7.26 - 7.19 (m, 1H), 6.79 - 6.70 (m, 2H), 6.28 - 6.22 (m, 1H), 5.92 (t, J = 3.5 Hz, 1H), 5.84 - 5.77 (m, 1H), 5.06 (d, J = 2.2 Hz, 2H), 2.49 - 2.44 (m, 4H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 172.4, 140.6 (d, J = 5.5 Hz), 135.9, 133.3, 132.24 (d, J = 117.3 Hz), 132.21 (d, J = 2.8 Hz), 132.1 (d, J = 2.8 Hz), 131.9, 131.81, 131.79, 130.80, 130.76 (d, J = 111.2 Hz), 128.49, 128.46, 128.4, 128.13, 128.11, 126.1, 124.3, 124.2, 122.1, 122.0, 121.3, 114.9, 114.8, 109.5, 107.0, 104.4, 66.1, 32.3, 19.9. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.28. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 34 H 30 N2O3P + 545.1989; Found 545.1981.[α] D 25= -500° (c = 0.10, CH2Cl2, 93% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 0.6 mL / min, l = 254 nm) t R = 15.1 min (major), 17.9 min(minor).

[0081] (8) Compound 3h, (S)-phenyl 3-(l-(2-(diphenylphosphoryl)-lH-indol-l- yl)-lH-pyrrol-2-yl)propanoate. Refer to the general procedure for the synthesis, the crude product was purified by column chromatography on silica gel (eluent: petroleum ether: ethyl acetate = 3: 1, by volume) to give 3h as brown oil in 57% yield.

[0082] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.82 - 7.73 (m, 2H), 7.71 - 7.57 (m, 3H), 7.57 - 7.51 (m, 2H), 7.49 - 7.36 (m, 4H), 7.32 (t, J = 7.8 Hz, 2H), 7.26 - 7.22 (m, 1H), 7.21 - 7.13 (m, 2H), 6.98 (d, J = 7.9 Hz, 2H), 6.78 (d, J = 8.2 Hz, 1H), 6.71 (d, J = 4.4 Hz, 1H), 6.22 - 6.14 (m, 1H), 5.91 - 5.84 (m, 2H), 2.72 - 2.55 (m, 2H), 2.53 - 2.35 (m, 2H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 171.2, 150.6, 140.7 (d, J = 5.4 Hz), 133.1, 132.6, 132.3 (d, J = 2.4 Hz), 132.2 (d, J = 2.3 Hz), 131.89, 131.87, 131.83, 131.81, 131.6, 130.9, 130.6 (d, J = 111.5 Hz), 129.3, 128.5, 128.4, 126.2, 125.7, 124.2, 124.2, 122.2, 122.1, 121.5, 121.4, 115.0, 114.9, 109.5, 107.0, 104.5, 32.4, 19.9. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.33. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 33 H 28 N2O3P + 531.1832; Found 531.1826.[a] D 25 = -1505° (c = 0.28, CH2Cl2, 97% ee). High performance liquid chromatography separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 0.6 mL / min, l = 254 nm) t R = 14.6 min (major), 16.6 min (minor).

[0083] (9) Compound 3i, 3-(l-(2-(diphenylphosphoryl)-lH-indol-l-yl)-lH-pyrrol-2- yl)propionic acid 2-bromophenyl ester. Refer to the general method for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3: 1, volume ratio) to give 3i as brown oil in 44% yield.

[0084] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.83 - 7.75 (m, 2H), 7.74 - 7.67 (m, 2H), 7.63 (d, J = 8.0 Hz, 1H), 7.60 - 7.53 (m, 3H), 7.50 - 7.45 (m, 4H), 7.31 - 7.27 (m, 2H), 7.20 (t, J = 7.4 Hz, 1H), 7.11 - 7.07 (m, 1H), 7.05 (dd, J = 8.1, 1.5 Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 6.75 (d, J = 4.4 Hz, 1H), 6.27 - 6.21 (m, 1H), 5.97 - 5.89 (m, 2H), 2.79 - 2.63 (m, 2H), 2.54 - 2.40 (m, 2H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 170.3, 152.7, 148.1, 140.7 (d, J = 5.8 Hz), 133.2, 133.0, 132.5, 132.33 (d, J = 2.1 Hz), 132.25 (d, J = 2.8 Hz), 132.2, 131.93, 131.91, 131.86, 131.8, 131.6, 130.9, 130.6 (d, J = 111.2 Hz), 128.9, 128.6, 128.5, 128.4, 127.2, 126.3, 124.3, 124.2, 123.8, 122.2, 122.1, 121.5, 116.3, 116.1, 115.1, 115.0, 109.5, 107.0, 104.7, 32.2, 19.8. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 16.23. High resolution mass spectrum: (ESI) m / z: [M+H] + Theoretical value C 33 H 27 BrN2O3P + 609.0937; Found 609.0931. [α]D 25 = -1785° (c = 0.28, CH2Cl2, 94% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 0.8 mL / min, l = 254 nm) t R = 12.4 min (minor), 13.4 min (major).

[0085] (10) Compound 3j, 2-tert-butylphenyl 3-(l-(2-(diphenylphosphoryl)-lH-indol-l- yl)-lH-pyrrol-2-yl)propanoate. Refer to the general procedure for the synthesis, the crude product was purified by column chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 3: 1, by volume) to give 3j as a brown oil in 56% yield.

[0086] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.80 (s, 2H), 7.72 - 7.61 (m, 3H), 7.59 - 7.52 (m, 2H), 7.45 (s, 4H), 7.34 (dd, J = 7.7, 1.9 Hz, 1H), 7.31 - 7.04 (m, 4H), 6.88 (dd, J = 7.8, 1.7 Hz, 1H), 6.82 - 6.78 (m, 1H), 6.75 (dd, J = 4.5, 0.9 Hz, 1H), 6.26 - 6.20 (m, 1H), 5.99 - 5.89 (m, 2H), 2.73 - 2.58 (m, 2H), 2.54 - 2.38 (m, 2H), 1.22 (s, 9H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 171.1, 149.1, 140.8, 140.67, 140.65 (d, J = 5.2 Hz), 140.6, 133.1, 132.3 (d, J = 2.8 Hz), 132.2 (d, J = 2.6 Hz), 132.1 (d, J = 117.9 Hz), 131.93, 131.91, 131.87, 131.8, 131.6, 130.9, 130.6 (d, J = 111.7 Hz), 128.6, 128.54, 128.47, 128.46, 127.1, 126.8, 126.2, 125.6, 124.3, 124.2, 123.9, 122.2, 122.1, 121.5, 115.0, 114.9, 109.5, 107.0, 104.7, 34.3, 33.0, 30.1, 19.9. Phosphine spectrum nuclear magnetic (162 MHz, CDC13) δ 15.37. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 37 H 36 N2O3P + 587.2458; Found 587.2448. [a] D 25 = -140° (c = 0.21, CH2Cl2, 93% ee). High performance liquid chromatography separation conditions (IA-H, isopropanol / n-hexane = 20 / 80, flow rate = 0.8 mL / min, l = 254 nm) t R= 12.3 min (minor), 13.5 min (major).

[0087] (11) Compound 3k, 2,4-di-tert-butylphenyl 3-(l-(2-(diphenylphosphoryl)-lH-indol-l- yl)-lH-pyrrol-2-yl)propanoate. Refer to the general procedure for the synthesis, the crude product was purified by column chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 3: 1, by volume) to give 3k as a brown oil in 75% yield.

[0088] H NMR (400 MHz, CDC13) δ 7.82 - 7.74 (m, 2H), 7.72 - 7.62 (m, 3H), 7.58 - 7.53 (m, 2H), 7.51 - 7.43 (m, 4H), 7.35 (d, J = 2.4 Hz, 1H), 7.29 - 7.23 (m, 1.5H), 7.23 - 7.16 (m, 2H), 6.81 (d, J = 8.3 Hz, 2H), 6.76 (d, J = 4.4 Hz, 1H), 6.33 - 6.23 (m, 1H), 6.02 - 5.85 (m, 2H), 2.72 - 2.57 (m, 2H), 2.52 - 2.37 (m, 2H), 1.30 (s, 9H), 1.22 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 171.2, 140.7 (d, J = 5.6 Hz), 147.9, 146.6, 139.7, 133.1, 132.3 (d, J = 2.9 Hz), 132.24 (d, J = 117.2 Hz), 132.19 (d, J = 2.9 Hz), 131.94, 131.91, 131.84, 131.81, 130.8, 130.7 (d, J = 111.3 Hz) 128.5, 128.4, 126.2, 124.3, 124.2, 124.0, 123.6, 123.1, 122.2, 122.1, 121.4, 115.0, 114.9, 109.5, 107.0, 104.7, 34.6, 34.5, 33.1, 31.4, 30.2, 19.9.31P NMR (162 MHz, CDC13) δ 15.32. High resolution mass spectrometry: (ESI) m / z: [M+H] + Calculated C 41 H44 N2O3P + 643.3084; found 643.3079.[α] D 25 = -259.3° (c = 0.38, CH2Cl2, 95% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 20 / 80, flow rate = 1.0 mL / min, l = 254 nm) t R = 7.2 min (minor), 8.8 min (major).

[0089] (12) Compound 3l, 3-(l-(2-(diphenylphosphinoyl)-lH-indol-l-yl)-lH-pyrrol-2- yl)propionic acid 3-methoxyphenyl ester. Refer to the general method for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3: 1, volume ratio) to give 3l as brown oil in 65% yield.

[0090] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.84 - 7.74 (m, 2H), 7.74 - 7.62 (m, 3H), 7.62 - 7.53 (m, 2H), 7.52 - 7.38 (m, 4H), 7.28 - 7.25 (m, 1.5H), 7.24 - 7.17 (m, 2H), 6.83 - 6.71 (m, 3H), 6.64 - 6.54 (m, 2H), 6.24 - 6.18 (m, 1H), 5.96 - 5.89 (m, 2H), 3.77 (s, 3H), 2.80 - 2.55 (m, 2H), 2.51 - 2.32 (m, 2H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 171.1, 160.4, 151.6, 140.7 (d, J = 5.6 Hz), 133.1, 132.32 (d, J = 2.9 Hz), 132.27 (d, J = 117.3 Hz), 132.2 (d, J = 2.8 Hz), 131.93, 131.91, 131.83, 131.81, 130.8, 130.7 (d, J = 111.4 Hz), 129.7, 128.6, 128.4, 126.2, 124.3, 124.2, 122.2, 122.1, 121.4, 115.0, 114.9, 113.7, 111.6, 109.5, 107.5, 107.0, 104.6, 55.4, 32.5, 19.9. Phosphine spectrum nuclear magnetic (162 MHz, CDC13) δ 15.41. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 34 H 30 N2O4P + 561.1938; Found 561.1932.[a] D 25 = -2170° (c = 0.28, CH2Cl2, 97% ee). High performance liquid chromatography separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 1.0 mL / min, l = 254 nm) t R = 10.4 min (major), 12.1 min (minor).

[0091] (13) Compound 3m, 3-(l-(2-(diphenylphosphoryl)-lH-indol-l-yl)-lH-pyrrol-2-yl)propanoic acid 3,5-dimethoxyphenyl ester. Refer to the general method for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3: 1, by volume), to give 3m as a brown oil in 55% yield.

[0092] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.83 - 7.75 (m, 2H), 7.72 - 7.60 (m, 3H), 7.60 - 7.52 (m, 2H), 7.52 - 7.40 (m, 4H), 7.31 - 7.25 (m, 1.5H), 7.24 - 7.18 (m, 1H), 6.80 (d, J = 8.2 Hz, 1H), 6.73 (d, J = 4.4 Hz, 1H), 6.31 (t, J = 2.3 Hz, 1H), 6.23 - 6.15 (m, 3H), 5.95 - 5.88 (m, 2H), 3.74 (s, 6H), 2.75 - 2.56 (m, 2H), 2.49 - 2.34 (m, 2H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 170.9, 140.7 (d, J = 5.5 Hz), 161.0, 152.1, 133.1, 132.3 (d, J = 2.9 Hz), 132.23 (d, J = 117.4 Hz), 132.17 (d, J = 2.8 Hz), 131.89, 131.87, 131.79, 131.77, 130.8, 130.7 (d, J = 111.3 Hz), 128.5, 128.4, 126.2, 124.3, 124.1, 122.2, 122.1, 121.4, 115.0, 114.8, 109.5, 107.0, 104.6, 100.1, 98.1, 55.4, 32.5, 19.9. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.36. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 35 H 32 N2O5P + 591.2043 ; Found 591.2040.[α] D 25= -2916.6° (c = 0.39, CH2Cl2, 98% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 0.7 mL / min, l = 254 nm) t R = 20.0 min (major), 23.9 min (minor).

[0093] (14) Compound 3n, 4-tert-butylphenyl 3-(l-(2-(diphenylphosphoryl)-lH-indol-l- yl)-lH-pyrrol-2-yl)propanoate. Refer to the general procedure for synthesis, the crude product was purified by column chromatography on silica gel (eluent: petroleum ether: ethyl acetate = 3: 1, volume ratio) to give 3n as brown oil in 47% yield.

[0094] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.83 - 7.75 (m, 2H), 7.73 - 7.62 (m, 3H), 7.60 - 7.52 (m, 2H), 7.52 - 7.41 (m, 4H), 7.39 - 7.32 (m, 2H), 7.29 - 7.23 (m, 1.5H), 7.23 - 7.17 (m, 1H), 6.93 - 6.89 (m, 2H), 6.84 - 6.79 (m, 1H), 6.77 - 6.72 (m, 1H), 6.25 - 6.18 (m, 1H), 5.97 - 5.88 (m, 2H), 2.73 - 2.27 (m, 4H), 1.30 (s, 9H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 171.3, 148.4, 148.2, 140.7 (d, J = 5.7 Hz), 133.2, 132.27 (d, J = 2.7 Hz), 132.25 (d, J = 117.3 Hz), 132.18 (d, J = 2.9 Hz), 131.9, 131.8, 130.8, 128.5, 128.4, 126.2, 124.3, 124.2, 122.2, 122.1, 121.4, 120.8, 115.0, 114.9, 109.5, 107.0, 104.6, 34.4, 32.5, 31.4, 20.0. Phosphorus spectrum nuclear magnetic (162 MHz, CDC13) δ 15.36. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 37 H36 N2O3P + 587.2458; Found 587.2451.[α] D 25 = 291.7° (c = 0.34, CH2Cl2, 98% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 20 / 80, flow rate = 0.8 mL / min, λ = 254 nm) t R = 7.1 min (major), 9.2 min (minor).

[0095] (15) Compound 3o, 3-(l-(2-(diphenylphosphinoyl)-lH-indol-l-yl)-lH-pyrrol-2- yl)propionic acid 4'-bromo-[l,l'-biphenyl]-4-yl ester. Refer to the general procedure for the synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3: 1, by volume) to give 3o as a brown oil in 48% yield.

[0096] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.85 - 7.73 (m, 2H), 7.73 - 7.61 (m, 3H), 7.63 - 7.32 (m, 12H), 7.32 - 7.26 (m, 1H), 7.24 - 7.18 (m, 1H), 7.17 - 7.04 (m, 2H), 6.84 - 6.78 (m, 1H), 6.73 (d, J = 4.3 Hz, 1H), 6.20 (t, J = 2.4 Hz, 1H), 5.93 (s, 1H), 2.89 - 2.30 (m, 4H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 171.2, 150.3, 140.7 (d, J = 5.5 Hz), 139.2, 137.6, 133.1, 132.6, 132.3 (d, J = 2.8 Hz), 132.2 (d, J = 2.7 Hz), 131.92, 131.85, 131.8, 131.7, 131.0, 130.6 (d, J = 111.2 Hz), 128.6, 128.54, 128.46, 127.9, 126.2, 124.3, 124.2, 122.2, 122.1, 122.0, 121.6, 121.4, 115.0, 114.9, 109.5, 107.1, 104.6, 32.5, 19.9. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 16.08. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 39 H 31 BrN2O3P + 685.1250; Found 685.1243.[a] D 25 = 615.2° (c = 0.47, CH2Cl2, 94% ee). High performance liquid chromatography separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 1.0 mL / min, λ = 254 nm) t R = 20.0 min (minor), 23.4 min (major).

[0097] (16) Compound 3p, i.e., (S)-3-(1-(5-chloro-2-(diphenylphosphoryl)-1H-indol-1-yl)-1H-pyrrol-2-yl)propanoic acid 2,4-di-tert-butylphenyl ester. Refer to the general method for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3:1, by volume), to give 3p as a brown oil in 75% yield.

[0098] hydrogen spectrum nuclear magnetic (600 MHz, CDCl3)) δ 7.80 - 7.74 (m, 2H), 7.70 - 7.64 (m, 2H), 7.61 - 7.55 (m, 3H), 7.51 - 7.44 (m, 4H), 7.35 (d, J = 2.4 Hz, 1H), 7.20 - 7.15 (m, 2H), 6.79 (d, J = 8.4 Hz, 1H), 6.72 (d, J = 8.8 Hz, 1H), 6.68 (dd, J = 4.4, 0.9 Hz, 1H), 6.24 (dd, J = 3.1, 1.8 Hz, 1H), 5.95 (t, J = 3.5 Hz, 1H), 5.91 (dt, J = 3.9, 1.3 Hz, 1H), 2.72 - 2.66 (m, 1H), 2.63 - 2.57 (m, 1H), 2.50 - 2.43 (m, 1H), 2.39 - 2.32 (m, 1H), 1.30 (s, 9H), 1.22 (s, 9H). Carbon spectrum nuclear magnetic (151 MHz, CDCl3)) δ 171.1, 148.0, 146.6, 139.7, 138.9 (d, J = 5.5 Hz), 134.3, 133.5, 133.0, 132.5 (d, J = 2.5 Hz), 132.4 (d, J = 2.8 Hz), 131.9, 131.8, 131.3, 130.5, 130.3 (d, J = 111.6 Hz), 128.6, 128.5, 127.8, 126.6, 125.1, 125.1, 124.0, 123.7, 123.0, 121.5, 121.3, 113.9, 113.9, 110.7, 107.3, 104.9, 34.6, 34.5, 33.0, 31.4, 30.1, 19.8. Phosphorus spectrum nuclear magnetic (243 MHz, CDCl3) δ 15.75. High resolution mass spectrum: (ESI) m / z: [M+H] + Theoretical value C41 H 43 ClN2O3P + 677.2694 ; Found 677.2688.[α] D 25 = 1361.1° (c = 0.51, CH2Cl2, 95% ee). High performance liquid chromatography separation conditions (IA-H, isopropanol / n-hexane = 20 / 80, flow rate = 1.0 mL / min, l = 254 nm) t R = 8.3 min (minor), 9.2 min(major).

[0099] (17) Compound 3q, (S)-3-(l-(2-(diphenylphosphoryl)-lH-indol-l-yl)-lH-pyrrol-2- yl)propanoic acid 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl ester. Refer to general method for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3: 1, volume ratio) to give 3q as brown oil in 45% yield.

[0100] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13) δ 7.82 - 7.74 (m, 2H), 7.72 - 7.61 (m, 3H), 7.60 - 7.51 (m, 2H), 7.51 - 7.40 (m, 4H), 7.33 - 7.25 (m, 1H), 7.23 - 7.18 (m, 1H), 6.77 (dd, J = 8.2, 1.0 Hz, 1H), 6.72 (dd, J = 4.5, 0.9 Hz, 1H), 6.17 (dd, J = 3.1, 1.8 Hz, 1H), 5.89 (t, J = 3.5 Hz, 1H), 7.23 - 7.18 (m, 1H), 5.83 - 5.78 (m, 1H), 4.29 (t, J = 6.6 Hz, 2H), 2.50 - 2.26 (m, 6H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 172.2, 140.7 (d, J = 5.5 Hz), 132.32 (d, J = 117.1 Hz), 132.26 (d, J = 2.9 Hz), 133.2, 132.2 (d, J = 2.9 Hz), 132.0, 131.92, 131.91, 131.82, 131.81, 130.9, 130.7 (d, J = 111.0 Hz), 128.53, 128.52, 128.41, 128.39, 126.1, 124.3, 124.2, 122.2, 122.1, 121.3, 114.9, 114.8, 109.4, 107.0, 104.4, 56.21, 56.17, 56.1, 32.1, 19.8. Phosphine spectrum nuclear magnetic (162 MHz, CDC13) δ 15.29. Fluorine spectrum nuclear magnetic (565 MHz, CDC13) δ -80.64, -113.60, -121.80, -122.77, -123.51, -126.04. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 35 H 27 F 13 N2O3P + 801.1546 ; Found 801.1541.

[0101] [α] D 25= -411.8° (c = 0.23, CH2Cl2, 91% ee). HPLC separation conditions (AD-H, isopropanol / n-hexane = 15 / 85, flow rate = 0.8 mL / min, l = 254 nm) t R = 7.3min (major), 8.2min (minor).

[0102] (18) Compound 3aa, (8R,9S,13S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17- decahydro-6H-cyclopenta[a]phenanthren-3-yl 3-(1-((S)-2-(diphenylphosphoryl)-1H- indol-1-yl)-1H-pyrrol-2-yl)propanoate. Refer to the general method for synthesis, the crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 3:1, volume ratio) to give 3aa as a brown oil in 45% yield.

[0103] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.86 - 7.76 (m, 2H), 7.71 - 7.66 (m, 2H), 7.63 (dt, J = 8.0, 1.0 Hz, 1H), 7.60 - 7.53 (m, 2H), 7.51 - 7.42 (m, 4H), 7.31 - 7.27 (m, 1H), 7.24 (s, 1H), 7.23 - 7.18 (m, 1H), 6.83 - 6.76 (m, 2H), 6.75 - 6.72 (m, 2H), 6.21 (dd, J = 3.1, 1.8 Hz, 1H), 5.93 (t, J = 3.5 Hz, 1H), 5.90 (dd, J = 4.0, 1.7 Hz, 1H), 2.92 - 2.85 (m, 2H), 2.71 - 2.64 (m, 1H), 2.63 - 2.56 (m, 1H), 2.54 - 2.47 (m, 2H), 2.43 - 2.37 (m, 2H), 2.30 - 2.24 (m, 1H), 2.18 - 2.10 (m, 1H), 2.06 - 1.94 (m, 4H), 1.64 - 1.56 (m, 2H), 1.54 - 1.44 (m, 3H), 0.90 (s, 3H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 220.8, 171.4, 148.4, 140.7 (d, J = 5.4 Hz), 137.8, 137.2, 133.1, 132.6, 132.3 (d, J = 2.3 Hz), 132.2 (d, J = 2.5 Hz), 131.88, 131.86, 131.82, 131.80, 131.6, 130.9, 130.6 (d, J = 111.7 Hz), 130.2, 128.5, 128.4, 126.3, 126.2, 124.2, 124.2, 122.2, 122.1, 121.5, 121.4, 118.6, 115.0, 114.9, 109.5, 107.0, 104.6, 50.3, 44.1, 37.9, 35.8, 32.4, 31.5, 29.6, 29.3, 26.3, 25.7, 21.5, 19.9, 13.8. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 16.09.High resolution mass spectrum: (ESI) m / z: [M+H]. + Calculated C 45 H 44 N2O4P + 707.3033; found 707.3026.[α] D 25 = 4122.4° (c = 0.64, CH2Cl2).

[0104] (19) Compound 3ab, i.e., (9R,10S,13R,14R)-17-((2R,5R,E)-5,6-dimethylhept-3- en-2-yl)-9,10,13,14-tetramethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H- cyclopenta[a]phenanthren-3-yl 3-(1-((S)-2-(diphenylphosphoryl)-1H-indol-1-yl)-1H- pyrrol-2-yl)propanoate. Refer to the general method for synthesis, the crude product was purified by column chromatography on silica gel (eluent: petroleum ether / ethyl acetate = 3:1, by volume) to give 3ab as a brown oil in 43% yield.

[0105] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.79 - 7.74 (m, 2H), 7.70 - 7.62 (m, 4H), 7.59 - 7.53 (m, 3H), 7.50 - 7.42 (m, 6H), 7.29 (t, J = 7.7 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 6.78 (d, J = 8.3 Hz, 1H), 6.75 (d, J = 4.3 Hz, 1H), 6.26 - 6.21 (m, 1H), 5.90 (t, J = 3.5 Hz, 1H), 5.84 - 5.78 (m, 1H), 5.59 - 5.52 (m, 1H), 5.43 - 5.33 (m, 1H), 5.25 - 5.15 (m, 2H), 4.69 - 4.56 (m, 1H), 2.47 - 2.19 (m, 6H), 2.10 - 2.00 (m, 3H), 1.92 - 1.82 (m, 3H), 1.53 - 1.44 (m, 3H), 1.35 - 1.28 (m, 3H), 1.03 (d, J = 6.7 Hz, 3H), 0.95 - 0.89 (m, 7H), 0.86 - 0.80 (m, 7H), 0.62 (s, 3H).Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 172.1, 141.5, 140.8 (d, J = 5.9 Hz), 138.5, 135.5, 133.5, 132.4 (d, J = 2.8 Hz), 132.3 (d, J = 2.5 Hz), 132.12 (d, J = 117.3 Hz), 131.9, 131.9, 131.8, 131.7, 130.9, 130.8 (d, J = 111.1 Hz), 128.5, 128.4, 126.1, 124.3, 124.2, 122.5, 122.2, 122.1, 121.3, 120.1, 116.2, 115.0, 114.9, 109.5, 107.8, 106.9, 104.3, 72.7, 55.6, 54.5, 46.0, 42.8, 40.4, 39.0, 37.8, 37.0, 36.6, 33.0, 32.5, 31.9, 31.4, 30.1, 28.3, 28.0, 22.9, 22.7, 21.1, 21.0, 19.9, 19.9, 19.6, 17.6, 16.1, 14.1, 12.0. Phosphine spectrum nuclear magnetic (162 MHz, CDC13) δ 15.52. High resolution mass spectrum: (ESI) m / z: [M+H]. + Calcd. C 55 H 67 N2O3P + 833.4806; Found 833.4794. [a] D 25 = -1238.46° (c = 0.37, CH2Cl2).

[0106] Example 5 This example provides a route for the synthesis of iridium-catalyzed enantioselective C-H alkylation of N-N axial chiral phosphines as shown below:

[0107] Different from Example 4, 2-(diphenylphosphino)-1,1'-biindolyl prepared in Example 3 was used as the substrate, and the specific reaction process was as follows: To a sealed reaction vial under nitrogen atmosphere, the alkyl acrylate (0.3 mmol, 3.0 equiv), [lr(coe)2Cl]2(4.5 mg, 0.005 mmol, 5 mol%) and ligand L7 (3.3 mg, 0.01 mmol, 10 mol%) were added successively, followed by toluene (0.5 mL). The reaction mixture was stirred at room temperature for 2 h, then 2-(diphenylphosphino)-1,1 '-binaphthyl (prepared in Example 3, 0.1 mmol, 1.0 equiv) dissolved in toluene (0.5 mL) was added. The reaction system was warmed to 150 °C and stirred for 24 h. After the reaction was completed, it was cooled to room temperature, hydrogen peroxide was added and the reaction was continued for 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure and the crude product was purified directly by column chromatography to give the target product. The resulting product was separated by preparative chiral high-performance liquid chromatography with the following results:

[0108] The resulting compound was characterized as follows: (1) Compound 4a, 4-(tert-butyl)phenyl 3-(2'-(diphenylphosphoryl)-[1,1 '- binaphthalen]-2-yl)propanoate, was synthesized according to the general experimental procedure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3:1 ) to give the target product 4a (brown oil, yield 46%).

[0109] Hydrogen spectrum nuclear magnetic (400 MHz, CDC13 δ 7.86 - 7.74 (m, 2H), 7.63 - 7.57 (m, 1H), 7.53 - 7.36 (m, 5H), 7.36 - 7.25 (m, 2H), 7.21 - 7.17 (m, 2H), 7.14 - 7.06 (m, 4H), 6.91 - 6.83 (m, 3H), 6.75 (d, J = 4.3 Hz, 1H), 6.66 - 6.60 (m, 1H), 6.58 - 6.52 (m, 1H), 6.28 (s, 1H), 6.10 (d, J = 8.1 Hz, 1H), 3.12 - 2.98 (m, 1H), 2.85 - 2.67 (m, 3H), 1.23 (s, 9H). Carbon spectrum nuclear magnetic (101 MHz, CDC13) δ 171.2, 148.5, 148.2, 140.5, 140.2 (d, J = 5.5 Hz), 136.5, 133.4 (d, J = 116.4 Hz), 132.3 (d, J = 2.9 Hz), 132.0, 131.9, 131.7 (d, J = 2.7 Hz), 131.5, 131.4, 130.8, 129.8, 128.7, 128.5, 128.4, 128.1, 128.0, 126.2, 125.7, 124.8, 124.7, 122.3, 122.3, 121.8, 120.8, 120.6, 119.9, 115.1, 115.0, 109.8, 108.7, 99.5, 34.4, 32.3, 31.4, 20.7. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 14.82. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 41 H 38 N2O3P + 637.2615; Found 637.2612.[α] D 25 = 2100.0° (c = 0.31, CH2Cl2, 91% ee). High performance liquid chromatography separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 1.0 mL / min, l = 254 nm) t R = 7.6 min (major), 9.2 min (minor).

[0110] (2) Compound 4b, [l,l'-biphenyl]-4-yl 3-(2'-(diphenylphosphoryl)-[l,l'-binolyl]-2- yl)propanoate, was synthesized according to the general experimental procedure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3: 1) to give the target product 4b (brown oil, yield 38%).

[0111] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.92 - 7.84 (m, 2H), 7.70 - 7.67 (m, 1H), 7.60 - 7.57 (m, 1H), 7.57 - 7.54 (m, 5H), 7.53 - 7.48 (m, 3H), 7.45 - 7.40 (m, 3H), 7.36 - 7.32 (m, 1H), 7.29 - 7.27 (m, 1H), 7.23 - 7.18 (m, 2H), 7.18 - 7.14 (m, 2H), 7.09 (d, J = 8.6 Hz, 2H), 6.99 - 6.94 (m, 2H), 6.83 (d, J = 4.3 Hz, 1H), 6.73 - 6.69 (m, 1H), 6.65 - 6.63 (m, 1H), 6.39 (d, J = 1.2 Hz, 1H), 6.17 (d, J = 8.1 Hz, 1H), 3.23 - 3.16 (m, 1H), 2.95 - 2.88 (m, 2H), 2.85 - 2.78 (m, 1H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 171.2, 145.0, 140.5, 140.3, 140.1 (d, J = 5.3 Hz), 138.9, 136.5, 133.7, 133.0, 132.3 (d, J = 2.8 Hz), 132.0, 131.9, 131.8 (d, J = 3.2 Hz), 131.7, 131.5, 131.4, 130.9, 129.6, 128.8, 128.7, 128.5, 128.4, 128.1, 128.1, 128.0, 127.3, 127.1, 126.3, 125.7, 124.8, 124.7, 122.3, 122.3, 121.8, 120.7, 119.9, 115.1, 115.0, 109.7, 108.7, 99.5, 32.3, 20.7. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 15.53. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 43 H 34 N2O3P + 657.2302; Found 657.2293.[α] D 25= 2833.3° (c = 0.30, CH2Cl2, 93% ee). HPLC separation conditions (IA-H, isopropanol / n-hexane = 30 / 70, flow rate = 1.0 mL / min, l = 254 nm) t R = 13.1 min (major), 16.6 min (minor).

[0112] Example 6 This example provides a route for the synthesis of enantioselective C-H alkylation reaction of N-N axial chiral phosphine as shown below:

[0113] In which, 2-(diphenylphosphino)-1-(2-methyl-1H-pyrrol-1-yl)-1H-indole prepared in Example 1 is used as a substrate, and the specific reaction process is as follows: Under a nitrogen atmosphere, a sealed reaction bottle was added in turn with an alkyl acrylate (0.3 mmol, 3.0 equivalents), [Ir(coe)2Cl]2(4.5 mg, 0.005 mmol, 5 mol%) and ligand L7 (3.3 mg, 0.01 mmol, 10 mol%), followed by the addition of toluene (0.5 mL). The reaction mixture was stirred at room temperature for 2 h, then 2-(diphenylphosphino)-1-(2-methyl-1H-pyrrol-1-yl)-1H-indole (prepared in Example 1, 0.1 mmol, 1.0 equivalent) dissolved in toluene (0.5 mL) was added. The reaction system was warmed to 150°C and stirred for 24 h. After the reaction was completed, it was cooled to room temperature, hydrogen peroxide was added and the reaction was continued for 0.5 h. After the reaction was complete, the solvent was removed under reduced pressure and the crude product was purified directly by column chromatography to obtain the target product. The results obtained by preparative chiral high-performance liquid chromatography separation are as follows:

[0114] The obtained compound was characterized as follows: (1) Compound 5a, namely 3-methoxyphenyl (S)-3-(1-(2-(diphenylphosphoryl)-1H-indol-1-yl)-5-methyl-1H-pyrrol-2-yl)propanoate, was synthesized according to the general experimental method. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3:1) to obtain the target product 5a (brown oil, yield 59%).

[0115] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.83 - 7.74 (m, 4H), 7.63 (d, J = 7.9 Hz, 1H), 7.59 - 7.52 (m, 2H), 7.51 - 7.44 (m, 4H), 7.29 - 7.16 (m, 3H), 6.78 - 6.70 (m, 3H), 6.61 - 6.58 (m, 1H), 6.57 - 6.50 (m, 1H), 5.82 (d, J = 3.8 Hz, 1H), 5.78 (d, J = 3.9 Hz, 1H), 3.77 (s, 3H), 2.64 - 2.56 (m, 1H), 2.51 - 2.43 (m, 1H), 2.38 - 2.28 (m, 2H), 1.56 (s, 3H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 171.1, 140.6 (d, J = 5.3 Hz), 160.4, 151.6, 132.6, 132.2, 132.2, 132.1, 132.1, 132.0, 132.0, 131.5, 131.3, 130.7 (d, J = 111.2 Hz), 130.5, 130.0, 129.7, 128.6, 128.5, 128.5, 128.4, 126.3, 124.4, 124.3, 122.2, 122.1, 114.9, 114.8, 113.7, 111.5, 109.6, 107.5, 104.8, 103.9, 55.4, 32.7, 20.3, 10.4. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 15.71. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 35 H 32 N2O4P + 575.2094; Found 575.2084.[α] D 25 = 1531.3° (c = 0.23, CH2Cl2, 92% ee). High performance liquid chromatography separation conditions (AD-H, isopropyl alcohol / n-hexane = 30 / 70, flow rate = 0.8 mL / min, l = 254 nm) t R = 18.1 min (major), 28.3 min (minor).

[0116] (2) Compound 5b, i.e., [l,l'-biphenyl]-4-yl 3-(l-(2-(diphenylphosphoryl)-lH-indol-l- yl)-5-methyl-lH-pyrrol-2-yl)propanoate, was synthesized according to the general experimental procedure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 3: 1) to give the target product 5b (brown oil, yield 59%).

[0117] Hydrogen spectrum nuclear magnetic resonance (600 MHz, CDC13) δ 7.84 - 7.75 (m, 4H), 7.64 (d, J = 7.9 Hz, 1H), 7.61 - 7.52 (m, 6H), 7.53 - 7.46 (m, 4H), 7.43 (t, J = 7.5 Hz, H), 7.34 (t, J = 7.4 Hz, 1H), 7.28 (d, J = 7.5 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.12 - 7.03 (m, 2H), 6.79 - 6.72 (m, 2H), 5.85 (d, J = 3.7 Hz, 1H), 5.80 (d, J = 3.8 Hz, 1H), 2.68 - 2.59 (m, 1H), 2.55 - 2.44 (m, 1H), 2.39 - 2.27 (m, 2H), 1.57 (s, 3H). Carbon spectrum nuclear magnetic resonance (151 MHz, CDC13) δ 171.3, 150.0, 140.6 (d, J = 5.9 Hz), 140.3, 138.8, 132.6, 132.27, 132.26, 132.25, 132.24, 131.5, 131.2, 130.7 (d, J = 111.7 Hz), 130.5, 130.0, 128.8, 128.6, 128.50, 128.48, 128.4, 128.1, 127.3, 127.1, 126.3, 124.44, 124.36, 122.2, 122.1, 121.8, 115.0 114.9, 109.6, 104.9, 103.9, 32.7, 20.3, 10.4. Phosphorus spectrum nuclear magnetic resonance (243 MHz, CDC13) δ 15.83. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 40 H 34 N2O3P + 621.2302; Found 621.2292.[a] D25 = 1100.0° (c = 0.20, CH2Cl2, 87% ee). HPLC separation conditions (AD-H, isopropanol / n-hexane = 20 / 80, flow rate = 0.8 mL / min, l = 254 nm) t R = 28.8 min (major), 37.8 min (minor).

[0118] Example 7 This example provides a route for the enantioselective C-H alkylation reaction synthesis of N-N axial chiral phosphine as shown below: 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole prepared in Example 1 was used as the substrate, and ligand L’ was used to replace the L7 ligand, unlike Example 4, and the specific synthesis process is as follows:

[0119] Under a nitrogen atmosphere, p-methoxyphenoxy acrylate (0.3 mmol, 3.0 equivalents), [Ir(coe)2Cl]2(4.5 mg, 0.005 mmol, 5 mol%) and ligand L’ (corresponding monophosphine can be directly prepared by not adding H2O2 in the compound 3h step in Example 4, 3.3 mg, 0.01 mmol, 10 mol%) were sequentially added to a sealed reaction bottle, followed by the addition of toluene (0.5 mL). The reaction mixture was stirred at room temperature for 2 h, then 2-(diphenylphosphino)-1-(1H-pyrrol-1-yl)-1H-indole (0.1 mmol, 1.0 equivalent) dissolved in toluene (0.5 mL) was added. The reaction system was warmed to 150°C and stirred for 24 h. After the reaction was completed, it was cooled to room temperature, hydrogen peroxide was added and the reaction was continued for 0.5 h. After the reaction was completed, the solvent was removed under reduced pressure, and the crude product was directly purified by column chromatography to obtain the target product. The effect of ligand L’ on the yield and enantioselectivity of the reaction was verified by preparative chiral high performance liquid chromatography separation, and it was further confirmed that it was the catalytic effect of the chiral ligand rather than the generated monophosphine.

[0120] Different from 97% ee under the condition of L7 ligand, it proves the effect of the ligand of the iridium catalyzed reaction, and excludes the interference of the generated monophosphine.

[0121] Example 8 This example provides a halogenation reaction of 2,4-di-tert-butylphenyl 3-[1-(2-(diphenylphosphoryl)-1H-indol-1-yl)-1H-pyrrol-2-yl]propanoate (compound 3k in Example 4), and the synthesis route is as follows:

[0122] To a mixture of compound 3k (0.1 mmol, 1.0 eq) and NBS (N-bromosuccinimide, 0.42 mmol, 4.2 eq) was added in a vial followed by dichloromethane (DCM, 1.0 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 h. After completion of the reaction, the solvent was removed under reduced pressure. The crude product was directly purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4: 1) to give a white oil in 81% yield.

[0123] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.91 - 7.82 (m, 2H), 7.77 - 7.71 (m, 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.58 - 7.53 (m, 1H), 7.55 - 7.48 (m, 2H), 7.48 - 7.42 (m, 2H), 7.36 (t, J = 7.7 Hz, 1H), 7.33 (d, J = 2.4 Hz, 1H), 7.28 - 7.22 (m, 1.7H), 7.16 (dd, J = 8.4, 2.4 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H), 6.83 (d, J = 4.4 Hz, 1H), 6.77 (d, J = 8.4 Hz, 1H), 2.93 - 2.81 (m, 2H), 2.79 - 2.70 (m, 1H), 2.53 - 2.45 (m, 1H), 1.29 (s, 9H), 1.17 (s, 9H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 170.4, 148.0, 146.5, 140.2 (d, J = 5.0 Hz), 139.7, 133.6, 133.0, 132.6, 132.6, 132.51, 132.49, 132.2, 132.0, 132.0, 131.3, 130.6, 129.6, 128.9, 128.64, 128.56, 128.4, 128.4, 126.9, 124.6, 124.5, 124.0, 123.6, 123.1, 122.9, 122.6, 116.4, 116.3, 109.6, 104.7, 101.8, 98.5, 34.6, 34.4, 33.2, 31.4, 30.1, 21.2. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 15.61. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 41 H 41 Br3N2O3P +877.0399; found 877.0381. [a]D25= 2066.7° (c = 0.30, CH2Cl2, 95% ee). HPLC separation conditions: (IA-H, isopropanol / n-hexane = 20 / 80, flow rate = 1.0 mL / min, l = 254 nm) t R = 7.2 min (minor), 12.9 min(major).

[0124] Example 9 This example provides the sulfuration reaction of 2,4-di-tert-butylphenyl 3-[1-(2- (diphenylphosphoryl)-1H-indol-1-yl)-1H-pyrrol-2-yl]propanoate (compound 3k in Example 4), whose synthetic route is as follows:

[0125] To a sealed tube was added 2,4-di-tert-butylphenyl acrylate (0.3 mmol, 3.0 equiv), [Ir(coe)Cl]2(4.5 mg, 0.005 mmol, 5 mol%), ligand L7 (3.3 mg, 0.01 mmol, 10 mol%) successively under nitrogen atmosphere, followed by the addition of toluene (Tol, 0.5 mL), and stirred at room temperature for 2 h. Then, compound 1 (0.1 mmol, 1.0 equiv) dissolved in 0.5 mL of toluene was added to the reaction system, and the temperature was raised to 150 °C for continued stirring for 4.5 h. After the reaction was completed, the temperature was cooled to room temperature, and the reaction was filtered through a silica gel pad. Elemental sulfur (S8, 0.12 mmol, 1.2 equiv) was added to the filtrate, and stirred at room temperature for 3 h. After the reaction was completed, the solvent was removed by evaporation under reduced pressure, and the crude product was purified directly by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1) to obtain the target product 8 (brown oil, 45.4 mg, yield 69%).

[0126] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.87 - 7.76 (m, 4H), 7.63 - 7.59 (m, 1H), 7.58 - 7.53 (m, 2H), 7.51 - 7.43 (m, 4H), 7.35 (d, J = 2.4 Hz, 1H), 7.26 - 7.22 (m, 1H), 7.23 - 7.16 (m, 2H), 6.83 (d, J = 8.4 Hz, 1H), 6.80 - 6.64 (m, 1H), 6.63 (d, J = 0.9 Hz, 1H), 6.04 (t, J = 2.4 Hz, 1H), 5.95 (d, J = 2.6 Hz, 2H), 2.80 - 2.66 (m, 2H), 2.63 - 2.47 (m, 1H), 2.41 - 2.32 (m, 1H), 1.30 (s, 9H), 1.23 (s, 9H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 171.2, 147.9, 146.6, 141.1 (d, J = 4.8 Hz), 139.8, 133.5, 132.53, 132.46, 132.1, 132.05, 132.03, 132.01, 131.91, 131.89, 131.85, 131.04, 130.96, 130.4, 128.6, 128.5, 126.1, 124.0, 123.6, 123.1, 122.2, 122.1, 121.3, 114.9, 114.8, 109.5, 106.9, 104.5, 34.6, 34.5, 32.9, 31.4, 30.2, 20.4. Phosphorus spectrum nuclear magnetic (243 MHz, CDC13) δ 28.82. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 41 H 44 N2O3PS + 659.2856; Found 659.2855. [a]D25 = -1137.5° (c = 0.23, CH2Cl2, 92% ee). High performance liquid chromatography separation conditions: (IA-H, isopropanol / n-hexane = 10 / 90, flow rate = 1.0 mL / min, l = 254 nm) t R = 5.4 min (minor), 7.0 min (major). Example 10 This example provides the conversion of 2,4-di-tert-butylphenyl 3-[1-(2- (diphenylphosphoryl)-1H-indol-1-yl)-1H-pyrrol-2-yl]propanoate (compound 3b) prepared in Example 4 to a carboxylic acid derivative, whose synthetic route is as follows:

[0127] To a sealed tube was added compound 3b (0.1 mmol, 1.0 equiv), lithium hydroxide (LiOH, 0.2 mmol, 2.0 equiv), tetrahydrofuran (THF, 0.5 mL) and water (H2O, 0.5 mL) under nitrogen atmosphere, stirred at room temperature for 12 h. After the reaction was completed, quenched with water, the organic phase was extracted with ethyl acetate (EtOAc) three times, the combined organic phase was concentrated under reduced pressure, the crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 2:1) to give brown oil in 80% yield.

[0128] Hydrogen spectrum nuclear magnetic (600 MHz, CDCl3) δ 7.57 - 7.52 (m, 1H), 7.41 - 7.31 (m, 10H), 7.22 - 7.18 (m, 1H), 7.18 - 7.12 (m, 1H), 6.92 - 6.86 (m, 1H), 6.38 - 6.36 (m, 1H), 6.33 - 6.30 (m, 1H), 6.08 - 6.04 (m, 1H), 6.01 - 5.97 (m, 1H), 2.54 - 2.47 (m, 1H), 2.44 - 2.34 (m, 3H). Carbon spectrum nuclear magnetic (151 MHz, CDCl3) δ 177.9, 139.7, 139.3 (d, J = 7.9 Hz), 134.7, 134.56, 134.61, 134.5, 133.9, 133.84, 133.79, 133.7, 132.6, 129.3, 129.2, 128.6, 128.54, 128.48, 125.9, 123.9, 121.8, 121.3, 120.9, 110.4, 108.9, 106.9, 104.8, 32.5, 20.0. Phosphorus spectrum nuclear magnetic (243 MHz, CDCl3) δ -30.4. High resolution mass spectrum: (ESI) m / z: [M+H] + Theoretical value C 27 H 24 N2O2P +439.1570; found 639.1560. [a]D25= -1586.7° (c = 0.21, CH2Cl2).

[0129] Example 11 This example provides the asymmetric allylic alkylation reaction catalyzed by N-N indole-pyridine monophosphine (any of the structures prepared in Examples 1-3 can be used) as ligand, and the synthetic route is as follows:

[0130] Under a nitrogen atmosphere, compound 26 (0.1 mmol, 1.0 equivalent), [{Pd(allyl)Cl}2] (0.004 mmol, 4 mol%), ligand L (Ligand in the synthetic route is compound 3e' which is prepared without adding H2O2 in step 3e, 0.008 mmol, 8 mol%), lithium acetate (LiOAc, 0.008 mmol, 8 mol%), bis(trimethylsilyl)amine (BSA, 0.2 mmol, 2.0 equivalent) and dichloromethane (DCM) were added into the reaction system successively, and stirred at room temperature for 0.5 h. Then compound 27 was added, and the stirring was continued at room temperature for 12 h. After the reaction was completed, water was added for quenching, the organic phase was extracted with ethyl acetate (EtOAc) for three times, the organic phases were combined, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1) to obtain white oil 28 with a yield of 90%.

[0131] Hydrogen spectrum nuclear magnetic (600 MHz, CDC13) δ 7.32 - 7.29 (m, 6H), 7.28 - 7.24 (m, 2.26H), 7.23 - 7.16 (m, 2H), 6.47 (d, J = 15.7 Hz, 1H), 6.33 (dd, J = 15.7, 8.6 Hz, 1H), 4.28 - 4.23 (m, 1H), 4.19 - 4.14 (m, 2H), 4.00 - 3.93 (m, 2H), 3.91 (d, J = 11.0 Hz, 1H), 1.20 (t, J = 7.1 Hz, 3H), 1.00 (t, J = 7.1 Hz, 3H). Carbon spectrum nuclear magnetic (151 MHz, CDC13) δ 167.8, 167.4, 140.3, 136.8, 131.6, 129.3, 128.6, 128.4, 128.0, 127.5, 127.1, 126.3, 61.6, 61.3, 57.7, 49.2, 14.1, 13.7. High resolution mass spectrum: (ESI) m / z: [M+H] + Calculated C 22 H 25 O4 + 353.1747; Found 353.1737. [a]D25= -1166.7° (c = 0.17, CH2Cl2, 85% ee). High performance liquid chromatography separation conditions: (IA-H, isopropanol / n-hexane = 05 / 95, flow rate = 1.0 mL / min, l = 254 nm) t R = 9.8 min (minor), 11.9 min (major).

[0132] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. An N-axis chiral monophosphine ligand, characterized in that, Its structure is shown in Equation I and Equation II: In Formula I and Formula II: Ar represents aryl, substituted aryl, or heteroaryl; R1-R3 are each independently selected from hydrogen, aryl, substituted aryl, heteroaryl, alkyl, olefinic and halogen.

2. The NN-axis chiral monophosphine ligand according to claim 1, characterized in that, The Ar is a five- to seven-membered nitrogen heterocyclic aryl, phenyl, or a phenyl group substituted with at least one of C1-C5 alkyl, C2-C5 olefinic, or halogen. R1-R3 are each independently selected from hydrogen, C1-C5 alkyl, C2-C5 olefin, five- to seven-membered nitrogen heterocyclic aryl, phenyl, and phenyl substituted by at least one of C1-C5 alkyl, C2-C5 olefin and halogen, wherein the halogen is fluorine, chlorine, bromine, or iodine.

3. The NN-axis chiral monophosphine ligand according to claim 1, characterized in that, The NN axial chiral monophosphine ligand is selected from any one of the following: 、 、 。 4. A method for preparing the NN-axis chiral monophosphine ligand according to any one of claims 1-3, characterized in that, Includes the following steps: (1) 2-Nitrobenzaldehyde compounds react with carbon tetrahalides to form 1,1-dihaloolefin compounds; (2) 1,1-Dihaloolefin compounds are reduced with a reducing agent to obtain amino compounds; (3) An intramolecular cyclization reaction is carried out between an amino compound and a base to prepare an indole skeleton compound; (4) The indole skeleton compound was subjected to an electrophilic amination reaction with a base and 4-nitrobenzene-1,2-diazooxy-4-hydroxybenzamide to prepare an indole derivative skeleton compound containing amino and halogen substitutions. (5) Indole derivative skeleton compounds are introduced into the indole ring under the catalysis of p-toluenesulfonic acid pyridinium; (6) Nucleophilic substitution reaction of indole derivative skeleton compounds containing pyrrole ring structure, metal alkyl compounds and diaryl phosphine halides is carried out to obtain NN axis chiral monophosphine ligands.

5. The method for preparing the N / N axial chiral monophosphine ligand according to claim 4, characterized in that, In step (1), the molar ratio of 2-nitrobenzaldehyde compounds to carbon tetrahalide is 1:(1-10), the reaction temperature is -30 to 100 °C, and the reaction time is 1 to 48 h; The carbon tetrahalide is one of carbon tetrachloride, carbon tetrabromide, and carbon tetraiodide; In step (2), the molar ratio of 1,1-dihaloolefin compound to reducing agent is 1:(1~20), the reaction temperature is 25-100℃, the reaction time is 1~48 h, and the reducing agent is iron powder or ferric chloride; In step (3) or step (4), the reaction occurs under the action of a catalyst and a base, and the molar ratio of amino compound, catalyst and base is 1:(1~10):(1~20); the reaction temperature is 25~100 ℃, the reaction time is 1-48 h, and the catalyst is a transition metal catalyst.

6. The method for preparing the N / N axial chiral monophosphine ligand according to claim 4, characterized in that, In step (6), the molar ratio of the indole skeleton compound, the metal alkyl compound, and 4-nitrobenzene-1,2-diazooxy-4-hydroxybenzamide is 1:(1-5):(1-5), the reaction temperature is -90 to 100 °C, and the reaction time is 0.5-48 h. The metal alkyl compound is one of alkyllithium and alkylmagnesium; The diarylphosphine halide is one of diarylphosphine chloride, diarylphosphine bromide, and diarylphosphine iodide.

7. The application of the NN-axial chiral monophosphine ligand according to any one of claims 1-3 in CH alkylation reactions and palladium-catalyzed coupling reactions.

8. A method for CH alkylation reaction, characterized in that, The process includes the following steps: adding alkyl acrylate, [Ir(coe)Cl]2, and ligand L7 to a solvent, stirring at room temperature, then adding the NN-axis chiral monophosphine ligand as described in any one of claims 1-3 as a substrate to carry out an alkylation reaction. After the reaction is completed, cooling to room temperature, adding an oxidant to carry out an oxidation reaction, and after the oxidation reaction is completed, removing the solvent and purifying the product to obtain the final product.

9. The method for CH alkylation reaction according to claim 8, characterized in that, The molar ratio of the alkyl acrylate to the NN-axial chiral monophosphine ligand is 3:(1-2). The structural formula of the ligand L7 is shown below: ; The structural formula of the alkyl acrylate is shown below: R is selected from hydrogen, C1-C5 alkyl, C2-C5 olefin, five- to seven-membered nitrogen heterocyclic aryl, phenyl, and phenyl substituted by at least one of C1-C5 alkyl, C2-C5 olefin and halogen; The alkylation reaction was carried out at a temperature of 140–160 °C for 1–3 h. The oxidation reaction takes 0.5 to 1 hour.

10. A method for a palladium-catalyzed coupling reaction, characterized in that, Using the NN-axis chiral monophosphine ligand as described in any one of claims 1-3 as the ligand for the palladium catalyst, the coupling reaction of acetate with indole derivative is catalyzed; The structural formula of the acetate is shown below: In the formula, Ar1 or Ar2 is independently selected from one of aryl, substituted aryl, and heteroaryl groups; The structural formula of the indole derivative is shown below: In the formula, R is selected from hydrogen, aliphatic substituent, alkyl, alkenyl, alkynyl and aryl.

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