Biaryl structure chiral N-quaternary ammonium salt pyridoxal catalyst and synthesis and application thereof

Abstract

The invention relates to a biaryl structure chiral N-quaternary ammonium salt pyridoxal catalyst and synthesis and application thereof, the general formula of the chemical structure of the catalyst is as follows: # imgabs0 # or # imgabs1 #, R1 and R2 are hydrogen or the following substituted or unsubstituted groups: C1-C24 alkyl, C3-C30 naphthenic base or aryl, C1-C24 carbonyl, C1-C24 sulfonyl or phosphoryl; r < 3 >, R < 4 > and R < 5 > are hydrogen or alkyl with 1-24 carbon atoms; x1, X2, X3 and X4 are respectively and independently N or CR, and R is H or C1-24 alkyl; and X5 is a fluorine ion, a chloride ion, a bromide ion, an iodide ion, a tetrafluoroborate anion, a trifluoroacetate anion, a trifluoromethanesulfonate anion, a methanesulfonate anion, a p-toluenesulfonate anion, a nitrate anion or a cyano anion. Compared with the prior art, the chiral N-quaternary ammonium salt pyridoxal catalyst disclosed by the invention is simple in synthesis process, and is successfully applied to bionic asymmetric SN2 reaction, nucleophilic substitution reaction of catalytic glycine ester to halide and the like.

Description

Technical Field

[0001] The invention belongs to the technical field of catalyst synthesis and relates to a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst and the synthesis and application thereof. Background Art

[0002] As important building blocks, non-natural α-amino acids are widely present in peptides, proteins, natural products and active pharmaceutical molecules. In addition, they can also be used as chiral building blocks in the synthesis of chiral catalysts and natural compounds. Therefore, it is of great significance to develop efficient methods for constructing chiral non-natural α-amino acids. The direct reaction of α-amino acid esters with halogenated alkanes is a potential efficient synthetic strategy for constructing non-natural quaternary carbon α-amino acids. However, α-amino acid esters contain both NH2 and α-CH reaction sites. Under the interference of inherent N-alkylation, regulating the reaction sites to achieve α-C-alkylation is the biggest factor hindering the direct reaction of α-amino acid esters with halogenated alkanes.

[0003] In recent years, the direct α-CH functionalization of primary amines using carbonyl catalysis has attracted widespread attention from chemists. Zhao Baoguo's research group has developed a variety of new and efficient naphthyl ring-pyridine axial chiral pyridoxal catalysts by simulating the reaction of L-threonine aldolase in vivo to catalyze the direct addition of glycine to aldehydes to form β-hydroxy-α-amino acids. They have been successfully applied to the addition reactions of various primary amine compounds to different electrophilic reagents [J.Chen, X.Gong, J.Li, Y.Li, J.Ma, C.Hou, G.Zhao, W.Yuan, B.Zhao, Science 2018,360,1438-1442; J.Ma,Q.Zhou,G.Song,Y.Song,G.Zhao,K.Ding,B.Zhao,Angew.Chem.Int.Ed.2021,60,10588-10592;A.Cheng,L .Zhang,Q.Zhou,T.Liu,J.Cao,G.Zhao,K.Zhang,G.Song,B.Zhao,Angew.Chem.Int.Ed.2021,60,20166-20172;J.Ma,B.Gao,G.Song,R.Z hang, Q. Wang, Z. Ye, W.-W. Chen, B. Zhao, Angew. Chem. Int. Ed. 2022, 61, e202200850; P. Ji, X. Liu, J. Xu. X. Zhang, J. Guo, W.-W. Chen, B. Zhao, Angew. Chem. Int. Ed. 2022, 61, e202206111; C. Hou, B. Peng, S. Ye, Z. Yin, J. Cao, X. Xiao, B. Zhao, Nat. Catal. 2022, 5, 1061-1068.]. In the above catalytic reactions, the CH functionalization of α-substituted primary amines has not been achieved due to the large steric hindrance. Therefore, the development of a new type of highly efficient chiral pyridoxal compound to catalyze the CH functionalization of α-substituted primary amines and apply it to the nucleophilic substitution reaction of α-amino acid esters on halogenated alkanes to synthesize chiral quaternary carbon α-amino acid ester compounds has important theoretical significance and great application potential. Summary of the invention

[0004] The purpose of the present invention is to provide a novel biaryl chiral N-quaternary ammonium salt pyridoxal catalyst.

[0005] Another object of the present invention is to provide a method for synthesizing the chiral pyridoxal catalyst.

[0006] The present invention also provides the use of the chiral pyridoxal catalyst, namely, to realize the asymmetric nucleophilic substitution reaction of unprotected α-amino acids on halogenated alkanes, and synthesize a series of non-natural quaternary carbon α-amino acid derivatives with high stereoselectivity.

[0007] The purpose of the present invention can be achieved by the following technical solutions:

[0008] One of the technical solutions of the present invention provides a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst, characterized in that its chemical structure is as follows:

[0009]

[0010] Furthermore, R 1 , R 2 It can be hydrogen or substituted or unsubstituted following groups: C1~C 24 Hydrocarbon, C3~C 30 Cycloalkyl or aryl, C1~C 24 The carbonyl group, C1~C 24 The alkyl group may be methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, 2,6-biphenyl, 3,5-biphenyl, (1-phenyl)ethyl, 1-naphthyl, 2-naphthyl, etc.; the substitution mentioned herein refers to substitution by the following substituents: halogen, C1-C8 alkyl, C3-C 12 The carbonyl group may be a cycloalkyl or aryl group, a C1-C8 carbonyl group, a C1-C8 sulfonyl or phosphoryl group, a C1-C8 alkoxy group or an amine group, wherein the carbonyl group refers to an aldehyde group, a keto carbonyl group, an ester carbonyl group, a carboxyl group or an amide group.

[0011] Furthermore, R 3 , R 4 , R 5 It can be hydrogen or C 1-24 The hydrocarbon group can be methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, trifluoromethyl, cyano, phenyl, benzyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, 2,6-biphenyl, 3,5-biphenyl, 1-naphthyl and 2-naphthyl, etc.

[0012] Furthermore, X1, X2, X3 and X4 can be N or CR, and R can be H or C. 1-24 The hydrocarbon group can be methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, trifluoromethyl, cyano, phenyl, benzyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, 2,6-biphenyl, 3,5-biphenyl, 1-naphthyl and 2-naphthyl, etc.

[0013] Furthermore, X5 can be a fluoride ion, a chloride ion, a bromide ion, an iodide ion, a tetrafluoroborate anion, a trifluoroacetate anion, a trifluoromethanesulfonate anion, a methanesulfonate anion, a p-toluenesulfonate anion, a nitrate anion, a cyanide anion, or the like.

[0014] The second technical solution of the present invention provides a method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst, comprising the following steps:

[0015] (1) Compound 5 was used as a raw material to obtain compound 6 by aldehyde protection;

[0016] (2) Compound 6 is coupled with compound 7 to obtain compound 8;

[0017] (3) Compound 8 is treated with an oxidant to obtain a carboxylic acid compound 9, which is then resolved with (S)-BINOL to obtain two configurations of compound 10;

[0018] (4) Compound 10 with a single configuration is subjected to the removal of BINOL under the action of a base and then acidified to obtain a chiral acid compound 9 with a single configuration;

[0019] (5) Single-configuration chiral acid compound 9 condenses with amine 11 to generate compound 12;

[0020] (6) Compound 12 is first N-alkylated with pyridine and then hydrolyzed under the action of an acid to obtain the final pyridoxal catalyst 1, which is the target product;

[0021] The overall preparation process can be seen in the following reaction flow:

[0022]

[0023] Furthermore, the process of step (1) is specifically as follows:

[0024] Compound 5 is used to protect the aldehyde group to obtain compound 6, wherein the molar ratio of compound 5 to the compound providing the protective group is 1:1 to 1:100, the reaction temperature is 0°C to 100°C, and the reaction time is 1 to 24 hours.

[0025] Furthermore, the process of step (2) is specifically as follows:

[0026] Add compound 6, compound 7, palladium complex, ligand and base to a reaction bottle, and then inject solvent under an inert gas protective atmosphere. After reaction, the coupling product compound 8 can be obtained, wherein the molar ratio of compound 6 to compound 7 is 1:1 to 1:5, the reaction temperature is -20°C to 120°C, and the reaction time is 1 to 24h.

[0027] Furthermore, the process of step (3) is specifically as follows:

[0028] In an organic solvent, compound 8 reacts with an oxidant to obtain carboxylic acid compound 9, wherein the molar ratio of compound 8 to the oxidant is 1:1 to 1:20, the reaction temperature is -20°C to 50°C, and the reaction time is 1 to 72 hours.

[0029] Furthermore, the process of step (4) is specifically as follows:

[0030] Add carboxylic acid compound 9, (S)-BINOL, condensing agent and base into a reaction container, then add solvent, and react to obtain two configurations of compound 10, wherein the molar ratio of carboxylic acid compound 9 to condensing agent is 1:1 to 1:5, the reaction temperature is -20°C to 50°C, and the reaction time is 1 to 48h;

[0031] In an organic solvent, compound 10 reacts with a base and then undergoes acidification to obtain chiral acid compound 9, wherein the molar ratio of compound 10 to the base is 1:1 to 1:10, the reaction temperature is -20°C to 120°C, and the reaction time is 1 to 72 hours.

[0032] Furthermore, the process of step (5) is specifically as follows:

[0033] Chiral acid compound 9 and amine 11 are reacted with a condensing agent to obtain compound 12, wherein the molar ratio of chiral acid compound 9 to amine 11 is 1:1 to 1:5, the reaction temperature is 0°C to 100°C, and the reaction time is 1 to 24 hours.

[0034] Furthermore, the process of step (6) is specifically as follows:

[0035] Compound 12 is first reacted with an alkylating agent to obtain an N-alkylated intermediate, and then reacted with an acid to obtain pyridoxal catalyst 1, wherein the molar ratio of compound 11 to the alkylating agent is 1:1 to 1:100, the reaction temperature is 0°C to 100°C, and the reaction time is 1 to 48 hours.

[0036] The third technical solution of the present invention provides an application of a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst, which is used for the asymmetric nucleophilic substitution reaction of unprotected α-amino acids on halogenated alkanes, and synthesizes a series of non-natural quaternary carbon α-amino acid derivatives with high stereoselectivity.

[0037] Furthermore, the catalyst is used for asymmetric nucleophilic substitution reactions of α-amino acids with a series of alkyl halides.

[0038] Specifically, compound 1 can be used to catalyze the synthesis of α-amino acids containing chiral quaternary carbon centers. The reaction can be described as follows: α-amino acid 2, alkyl halide 3 and pyridoxal catalyst 1 undergo an asymmetric nucleophilic substitution reaction under the action of a base and an additive to generate the corresponding chiral quaternary carbon α-amino acid 4, which contains two different configurations (R) and (S). The general formula for synthesizing chiral quaternary carbon α-amino acid 4 from pyridoxal 1, α-amino acid 2 and alkyl halide 3 is shown below:

[0039]

[0040] More specifically, the synthesis steps for preparing chiral quaternary carbon α-amino acid 4 from pyridoxal 1 are as follows: weigh pyridoxal 1, α-amino acid 2, alkyl halide 3, base and additives into a reaction bottle, and then add the corresponding solvent into the bottle. After the reaction is completed, the corresponding chiral quaternary carbon α-amino acid 4 is obtained.

[0041] In the above preparation method, the molar ratio of α-amino acid 2 and alkyl halide 3 is 0.5:1 to 5:1, and the molar ratio of pyridoxal 1 and alkyl halide 3 is 0.01:1 to 0.5:1. The reaction temperature is -10 to 100°C, and the reaction time is 1 to 72 hours.

[0042] Where R 6 It can be hydrogen, substituted or unsubstituted following groups: C1~C 24 Hydrocarbon, C3~C 30 Cycloalkyl or aryl, C1~C 24 The carbonyl group, C1~C 24 sulfonyl or phosphoryl; wherein the substitution refers to substitution by the following substituents: halogen, C1-C8 hydrocarbon, C3-C 12 The carbonyl group may be a cycloalkyl or aryl group, a C1-C8 carbonyl group, a C1-C8 sulfonyl or phosphoryl group, a C1-C8 alkoxy group or an amine group, wherein the carbonyl group refers to an aldehyde group, a keto carbonyl group, an ester carbonyl group, a carboxyl group or an amide group.

[0043] R 7 It can be hydrogen, substituted or unsubstituted following groups: C1~C 24 Hydrocarbon, C3~C 30 Cycloalkyl or aryl, C1~C 24 The carbonyl group, C1~C 24 sulfonyl or phosphoryl; wherein the substitution refers to substitution by the following substituents: halogen, C1-C8 hydrocarbon, C3-C 12 The carbonyl group may be a cycloalkyl or aryl group, a C1-C8 carbonyl group, a C1-C8 sulfonyl or phosphoryl group, a C1-C8 alkoxy group or an amine group, wherein the carbonyl group refers to an aldehyde group, a keto carbonyl group, an ester carbonyl group, a carboxyl group or an amide group.

[0044] X6 can be various leaving groups, including halogen atoms, methanesulfonate, trifluoromethanesulfonate, benzenesulfonate, p-toluenesulfonate, trifluoroacetate, and the like.

[0045] The above-mentioned solvents are independently selected from any one or more of the following solvents: water, methanol, ethanol, isopropanol, n-propanol, n-butanol, trifluoroethanol, benzene, toluene, xylene, trimethylbenzene, acetonitrile, ether, tetrahydrofuran, ethylene glycol dimethyl ether, chloroform, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N-methylpyrrolidone, etc.

[0046] The above-mentioned base is independently selected from any one or more of the following bases: sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, calcium hydride, potassium fluoride, triethylamine, diisopropylamine, diisopropylethylamine, tetramethylethylenediamine, N,N-dimethylaniline, N,N-diethylaniline, 1,4-diazabicyclooctane (DABCO), diazabicyclododecane (DBU), n-butyllithium, 1,4-dimethylpiperazine, 1-methylpiperidine, 1-methylpyrrole, quinoline or pyridine, etc.

[0047] The above-mentioned additive can be one selected from the following Lewis acids: zinc fluoride, zinc chloride, zinc bromide, zinc iodide, zinc sulfate, zinc phosphate, basic zinc carbonate, zinc hydroxide, zinc acetate, zinc telluride, zinc benzoate, zinc trifluoroacetate, zinc pivalate, zinc p-toluenesulfonate, zinc gluconate, zinc stearate, magnesium fluoride, magnesium chloride, magnesium bromide, magnesium carbonate, magnesium phosphate, magnesium trifluoromethanesulfonate, scandium trifluoromethanesulfonate, dysprosium trifluoromethanesulfonate, copper trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, ferric chloride, calcium chloride, calcium bromide, etc.

[0048] Compared with the prior art, the present invention has the following advantages:

[0049] (1) Pyridoxal is a very important class of compounds with good biological activity. In biological systems, it is a coenzyme of many biological enzymes and can catalyze the addition of glycine derivatives to aldehydes to synthesize α-hydroxy-β-amino acid derivatives. The present invention has developed a series of novel chiral N-quaternary ammonium salt pyridoxal catalysts by simulating the enzyme catalysis process in vivo, successfully realizing the asymmetric nucleophilic substitution reaction of unprotected α-amino acids to halogenated alkanes, and realizing the rapid and effective synthesis of chiral non-natural quaternary carbon α-amino acid derivatives.

[0050] (2) The chiral pyridoxal catalyst 1 developed in the present invention can be prepared by multi-step reactions of cheap and readily available raw materials, with mild reaction conditions, and is generally easy to scale up and can be prepared on a large scale.

[0051] (3) The biomimetic asymmetric affinity substitution reaction catalyzed by the N-quaternary ammonium salt pyridoxal catalyst 1 of the present invention is a new method for preparing non-natural quaternary carbon α-amino acid derivatives. The method simulates the enzyme catalysis process in the organism: the chiral pyridoxal catalyst 1 condenses with the α-amino acid 2 to form an aldimine, and the αC-H of the aldimine is deprotonated to obtain an enolate anion intermediate, and then the halogenated alkane 3 is subjected to a nucleophilic substitution reaction, and after hydrolysis, a quaternary carbon α-amino acid 4 is generated, and the chiral pyridoxal catalyst 1 is regenerated to complete the catalytic cycle process.

[0052] (4) The reaction conditions catalyzed by pyridoxal catalyst 1 in the present invention are very mild and not very sensitive to water and air. It can be carried out in water, the reaction is stable, easy to operate, the product selectivity is good, and the yield is good. By adjusting the chemical selectivity, α-C alkylation is successfully achieved under NH2 unprotected conditions. This is an effective method for preparing non-natural quaternary carbon α-amino acid derivatives. DETAILED DESCRIPTION

[0053] The present invention is described in detail below in conjunction with specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and a specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0054] In the following embodiments,

[0055] If there is no special description of raw materials or processing techniques, it means that they are all conventional commercially available raw materials or conventional processing techniques in the art.

[0056] Example 1: Synthesis of Compound 6

[0057]

[0058] Compound 5 (20.00 g, 76.89 mmol), TsOH·H2O (1.46 g, 7.69 mmol), CH(OEt)3 (150 mL) were added to a 500 mL reaction bottle with a stirrer in sequence and refluxed for 13 hours. After cooling to room temperature, saturated NaHCO3 solution was added dropwise until pH~8, 100 mL of water was added to dilute, and the organic solvent was removed by vortexing. Extracted with dichloromethane three times (150 mL×3), the organic phases were combined, dried over anhydrous Na2SO4, filtered, and concentrated by column chromatography to obtain compound 6 (yellow oily liquid, 17.72 g, 76% yield)

[0059] Yellow oil; 1 H NMR (400MHz, CDCl3) δ8.27(s,1H),5.74(s,1H),5.17(s,2H),3.48(s,3H),3.45(s,6H),2.62(s,3H);13 C NMR (100MHz, CDCl3) δ152.3,150.0,137.3,134.9,121.0,104.4,96.2,56.4,56.2,25.4; HRMS m / z Calcd.for C 11 H 17 BrNO4(M+H + ):306.0335;Found:306.0341.

[0060] The synthesis process of compound 5 can be found in the literature: Chen, J.; Gong, X.; Li, J.; Li, Y.; Ma, J.; Hou, C.; Zhao, G.; Yuan, W.; Zhao, B. Carbonyl catalysis enables a biomimetic asymmetric Mannich reaction. Science 2018, 360, 1438-1442.

[0061] Example 2: Synthesis of Compound 8

[0062]

[0063] Compound 6 (2.62 g, 8.59 mmol), commercially purchased compound 7 (1.55 g, 10.31 mmol), Pd2(dba)3 (0.196 g, 0.22 mmol), ligand Ruphos (0.179 g, 0.43 mmol) and KF (1.49 g, 25.77 mmol) were added to a 100 mL reaction bottle in sequence, a stirring bar was added, a rubber stopper was put on, N2 was replaced three times, and then 1,4-dioxane (24 mL) and water (3 mL) were injected with a syringe. The reaction system was stirred at room temperature for 30 minutes, then transferred to 100 ° C and stirred overnight. Cooled to room temperature, filtered, concentrated the filtrate, and column chromatography obtained Compound 8 (brown oily liquid, 2.81 g, yield 99%).

[0064] Brown oil; 1 H NMR (400MHz, CDCl3) δ9.63 (s, 1H), 8.48 (s, 1H), 8.02 (dd, J = 7.6, 1.2

[0065] Hz,1H),7.62(td,J=7.6,1.2Hz,1H),7.52(t,J=7.2Hz,1H),7.21(dd.J=7.2,0.8Hz,1H),5. 37(dd,J=9.6,6.8Hz,2H),5.25(s,1H),3.55(s,3H),3.17(s,3H),3.14(s,3H),2.13(s,3H); 13 C NMR (100MHz,CDCl3)δ 13 C HRMS m / z Calcd.for C 18 H 22 NO5(M+H + ):332.1492;Found:332.1505.

[0066] Example 3: Synthesis of Compound 9

[0067]

[0068] Compound 8 (5.72 g, 17.3 mmol) was dissolved in t In a mixed solvent of BuOH (30 mL) and DCM (15 mL), under ice bath for 10 minutes, slowly add an aqueous solution (60 mL) of NaClO2 (10.9 g, 121 mmol) and NaH2PO4·H2O (21.6 g, 138 mmol), and add 2-methyl-2-butene (9.69 g, 138 mmol). Return to room temperature and stir overnight. Add 50 mL of water and 50 mL of ethyl acetate for separation. The aqueous phase is extracted with DCM (50 mL×3). Combine the organic phases, dry over anhydrous Na2SO4, filter, and concentrate the filtrate to obtain compound (±)-9 (light yellow solid, 5.93 g, yield 99%, 85%).

[0069] Pale yellow solid; Mp156-157℃; 1H NMR (400MHz, CDCl3) δ10.01(brs,1H),8.29(s,1H),8.10(dd,J=8.0,1.2Hz,1H),7.54(td,J=7.6,1.6Hz,1H),7.48(td, J=7.6,1.6Hz,1H),7.11(dd,J=7.6,1.2Hz,1H),5.25-5.17(m,2H),4.99(s,1H),3.49(s,3H),3.19(s,6H),2.07(s,3H); 13 C NMR(100MHz, CDCl3)δ169.6,150.1,150.0,137.7,137.4,135.0,134.4,131.8,131.4,131.0,130.7,128.2,103.2,95.9,56.4,56.1,55.7,21.3; m / zCalcd.for C 18 H 22 NO6(M+H + ):348.1442;Found:348.1450.

[0070] Example 4: Synthesis of Compound 10

[0071]

[0072] Compound (±)-9 (5.93 g, 17.1 mmol), (S)-(-)-1,1'-binaphthol (BINOL, 5.44 g, 19.0 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl, 6.61 g, 34.6 mmol) and 4-dimethylaminopyridine (DMAP, 0.422 g, 3.46 mmol) were dissolved in DCM (60 mL), and N-methylmorpholine (NMM, 4.37 g, 43.2 mmol) was injected. After stirring at room temperature for 13 hours, 100 mL of water was added to quench the reaction. Subsequently, the mixture was extracted with DCM (100 mL×3), the organic phases were combined, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated. Column chromatography gave compound (R,S)-10 (white solid, 4.20 g, yield 40%).

[0073] White solid; Mp86-87℃; [α] D 25 = -107.6 (c = 0.10, CHCl3); 1 H NMR (400MHz,CDCl3)

[0074] δ8.29(s,1H),7.98(d,J=8.8Hz,1H),7.92(d,J=8.0Hz,1H),7.82(d,J=8.8Hz,1H) ,7.78(d,J=7.6Hz,1H),7.51-7.42(m,3H),7.34-7.27(m,2H),7.26-7.23(m,3H), 7.22(d,J=3.2Hz,2H),7.05(d,J=7.6Hz,1H),6.94(d,J=8.0Hz,1H),5.37(brs,1H ),5.24(s,2H),5.02(s,1H),3.55(s,3H),3.15(s,3H),3.12(s,3H),1.59(s,3H); 13 C NMR (100MHz, CDCl3) δ166.1,151.9,150.7,149.4,148.1,139.5,137.0,1 35.1,133.7,133.5,133.0,132.3,132.2,130.9,130.8,130.5,130.4,12 9.0,128.9,128.3,127.9,127.8,127.5,127.0,126.3,125.8,124.7,123 .7,123.4,121.5,118.2,114.1,102.7,96.0,56.4,55.9,55.6,22.3; HRMS m / z Calcd.for C 38 H 34 NO7(M+H + ):616.2330;Found:616.2346.

[0075] Example 5: Synthesis of Compound (R)-9

[0076]

[0077] Compound (R, S)-10 (4.20 g, 6.83 mmol) was dissolved in a mixed solvent of EtOH (25 mL) and H2O (50 mL), and KOH (2.30 g, 41.0 mmol) was added. After reflux for 4 hours, the organic solvent was removed by vortexing, and 50 mL of water was added. The aqueous solution was washed with a mixed solvent of ethyl acetate and petroleum ether (1:3) (100 mL×3), the aqueous phase was collected, acidified to pH~4-5 with 1.0 M hydrochloric acid, and then extracted with DCM (100 mL×5), the organic phases were combined, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated to obtain compound (R)-9 (yellow solid, 2.30 g, yield 97%).

[0078] (R)-9:Yellow solid; Mp156-157℃; [α] D 25 = -19.0 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ9.06 (brs, 1H), 8.30 (s, 1H), 8.14-8.06 (m, 1H), 7.58-7.46 (m, 2H), 7.11 (dd, J = 7. 2,0.8Hz,1H),5.22(dd,J=10.4,6.8Hz,2H),5.03-4.99(m,1H),3.49(s,3H),3.20(m,6H),2.09(s,3H); 13 C NMR(100z MHz, CDCl3)δ169.4,150.2,149.8,137.7,137.4,134.9,134.2,131.7,131.5,131.0,130.8,128.3,103.1,95.9,56.5,56.1,55.8,21.0; HRMSm / z Calcd.for C 18 H 22 NO6(M+H + ):348.1442;Found:348.1449.

[0079] Example 6: Synthesis of Compound (R)-12

[0080]

[0081] Compound (R)-9 (1.00 g, 2.88 mmol), 11 [2] (1.39 g, 5.76 mmol), EDCl (2.20 g, 11.5 mmol), 1-hydroxy-7-azobenzotriazole (HOAt, 1.56 g, 11.5 mmol) were dissolved in freshly distilled DCM (10 mL), and N,N-diisopropylethylamine (DIPEA 0.214 g, 2.115 mmol) was injected. After stirring at room temperature for 15 hours, 30 mL of water was added to quench the reaction. Subsequently, the mixture was extracted with DCM (30 mL × 3), the organic phases were combined, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated and column chromatography was performed to obtain compound (R)-12 (light yellow oil, 1.05 g, yield 64%).

[0082] Brown solid; Mp61-62℃; [α] D 25 = -16.5 (c = 0.10, CHCl3); 1H NMR(400MHz, CDCl3)δ9.91(s,1H),9.18(s,1H),7.74-7.63(m,1H),7.62-7.53(m,2H),7.38(dd,J=7.8,1.6Hz,1H),4.39(s,3H),3.36-3.25(m,1H), 3.20-3.05(m,2H),3.04-2.93(m,1H),2.50(s,3H),1.64-1.50(m,2H),1.2 8-1.19(m,8H),1.14-1.06(m,4H),1.04-0.94(m,4H),0.88-0.83(m,12H); 13 C NMR (100MHz, CDCl3) δ190.9,170.0,157.8,144.8,139.7,137.3,135.6,132.0,131.3,130.6,129.8,129 .0,127.1,52.2,49.1,45.6,34.7,33.9,33.7,33.4,33.1,19.9,19.4,19.2,18.7,14.4,14.3,14.2; HRMS m / z Calcd.for C 31 H 47 N2O3(MI - ):495.3581;Found:495.3592.

[0083] The synthesis process of compound 11 can be found in the literature: Coeck, R.; De Vos, DE. One-pot reductive amination of carboxylic acids: a sustainable method for primary amine synthesis. Green Chem. 2020, 22, 5105-5114.

[0084] Example 7: Synthesis of Compound (R)-1

[0085]

[0086] Compound (R)-12d (1.05 g, 1.84 mmol) was dissolved in CH3CN (10 mL), and then iodomethane (MeI, 10.4 g, 73.6 mmol) was injected. After stirring at room temperature for 4 hours, the mixture was concentrated and column chromatography was performed to obtain N-methyl intermediate (light yellow solid, 1.21 g, yield 92%). The intermediate (1.21 g, 1.70 mmol) was dissolved in THF (10 mL), and then 1.0 M hydrochloric acid solution (10 mL) was injected. The mixture was stirred overnight at 50°C, the organic solvent was removed by rotation, H2O (10 mL) was injected, and DCM was extracted (20 mL×3), the organic phases were combined, dried over anhydrous Na2SO4, filtered, and the filtrate was concentrated to obtain compound (R)-1d (brown solid, 1.03 g, yield 97%), with a two-step yield of 90%.

[0087] Mp61-62℃; [α] D 25 = -16.5 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ9.91(s,1H),9.18(s,1H),7.74-7.63(m,1H),7.62-7.53(m,2H),7.38(dd,J=7.8,1.6Hz,1H),4.39(s,3H),3.36-3.25(m,1H), 3.20-3.05(m,2H),3.04-2.93(m,1H),2.50(s,3H),1.64-1.50(m,2H),1.2 8-1.19(m,8H),1.14-1.06(m,4H),1.04-0.94(m,4H),0.88-0.83(m,12H); 13 CNMR (100MHz, CDCl3) δ190.9,170.0,157.8,144.8,139.7,137.3,135.6,132.0,131.3,130.6,129.8,129 .0,127.1,52.2,49.1,45.6,34.7,33.9,33.7,33.4,33.1,19.9,19.4,19.2,18.7,14.4,14.3,14.2; HRMS m / z Calcd.for C 31 H 47 N2O3(MI-):495.3581; Found:495.3592.

[0088] Example 8: Synthesis of quaternary carbon α-amino acid ester 4a catalyzed by chiral pyridoxal catalyst (R)-1a

[0089]

[0090] Chiral pyridoxal catalyst (R)-1a (0.0125 g, 0.020 mmol) and Zn3(PO4)2 (7.7 mg, 0.02 mmol) were added to a 2 mL reaction bottle, Et2O (0.3 mL) was injected, tert-butyl alanine ester 2a (0.0436 g, 0.30 mmol) was injected, a stirring bar was added, and the stopper was covered and stirred at room temperature for 1 hour. Then H2O (0.10 mL), DIPEA (0.0388 g, 0.3 mmol) and benzyl bromide 3a (49.4 mg, 0.20 mmol) were added in sequence and stirred at room temperature for 10 hours. Then, hydroxylamine aqueous solution (0.50 mL, 50 wt.% in H2O) was added and stirred for 30 minutes to quench the reaction. Aqueous ammonia (5.0 mL, 25-28 wt. % in water) was added, and the mixture was extracted with dichloromethane (15 mL×4). The organic phases were combined, dried over anhydrous Na2SO4, filtered, and purified by column chromatography to obtain compound 4a (yellow solid, 0.060 g, yield 96%).

[0091] The ee value of 4a was 99% as determined by HPLC analysis of its benzoyl derivative.

[0092] Yellow solid; Mp49-50℃; [α] D 25 = -20.7 (c = 0.25, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.60-7.55(m,2H),7.52(d,J=8.4Hz,2H),7.43(td,J=8.4,1.6Hz,2H),7.36-7. 28(m,3H),3.16(d,J=13.2Hz,1H),2.83(d,J=13.2Hz,1H),1.72(brs,2H),1.48(s,9H),1.38(s,3H); 13 C NMR (100MHz, CDCl3) δ176.4,141.0,139.8,136.0,130.8,128.9,127.3,127.1,127.0,81.3,59.0,46.1,28.2,27.1; HRMS m / z Calcd.for C 20 H 26 NO2(M+H + ):312.1958;Found:312.1958.

[0093] Example 9: Synthesis of quaternary carbon α-amino acid ester 4a catalyzed by chiral pyridoxal catalyst (R)-1b

[0094]

[0095] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that (R)-1b is used to replace (R)-1a, and the other conditions are the same as Example 8. Column chromatography gave compound 4a (yellow solid, 0.0191 g, yield 31%).

[0096] The ee value of 4a was 89% as determined by HPLC analysis of its benzoyl derivative.

[0097] Example 10: Synthesis of quaternary carbon α-amino acid ester 4a catalyzed by chiral pyridoxal catalyst (R)-1c

[0098]

[0099] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that (R)-1c is used to replace (R)-1a, and the other conditions are the same as Example 8. Column chromatography gave compound 4a (yellow solid, 0.0891 g, yield 79%).

[0100] The ee value of 4a was 89% as determined by HPLC analysis of its benzoyl derivative.

[0101] Example 11: Synthesis of quaternary carbon α-amino acid ester 4a catalyzed by chiral pyridoxal catalyst (R)-1d

[0102]

[0103] The addition amount of each component reagent and the reaction steps are shown in Example 8. Compared with Example 8, the only difference is that (R)-1d is used to replace (R)-1a and ZnCl2 is used to replace Zn3(PO4)2. The other conditions are the same as Example 8. Column chromatography gave compound 4a (yellow solid, 0.0386 g, yield 62%).

[0104] The ee value of 4a was 78% as determined by HPLC analysis of its benzoyl derivative.

[0105] Example 12: Synthesis of quaternary carbon α-amino acid ester 4a catalyzed by chiral pyridoxal catalyst (R)-1d

[0106]

[0107] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that (R)-1d is used to replace (R)-1a and K2CO3 is used to replace DIPEA. The other conditions are the same as Example 8. Column chromatography gave compound 4a (yellow solid, 0.0193 g, yield 23%).

[0108] The ee value of 4a was 85% as determined by HPLC analysis of its benzoyl derivative.

[0109] Example 13: Synthesis of quaternary carbon α-amino acid ester 4a catalyzed by chiral pyridoxal catalyst (R)-1d

[0110]

[0111] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that (R)-1d is used instead of (R)-1a and EtOH is used instead of Et2O. The other conditions are the same as Example 8. Column chromatography gave compound 4a (yellow solid, 0.0504 g, yield 71%).

[0112] The ee value of 4a was 81% as determined by HPLC analysis of its benzoyl derivative.

[0113] Example 14: Synthesis of quaternary carbon α-amino acid ester 4b catalyzed by chiral pyridoxal catalyst (R)-1a

[0114]

[0115] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3b is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4b (yellow oily liquid, 0.0393 g, yield 84%).

[0116] The ee value of 4b was 99% as determined by HPLC analysis of its benzoyl derivative.

[0117] Yellow oil; [α] D 25 = -23.9 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.31-7.19(m,5H),3.11(d,J=13.2Hz,1H),2.77(d,J=13.2Hz,1H),1.59(brs,2H),1.46(s,9H),1.34(s,3H); 13C NMR (100MHz, CDCl3) δ176.4,137.0,130.3,128.3,126.9,81.3,58.9,46.5,28.1,27.2; HRMS m / z Calcd.for C 14 H 22 NO2(M+H + ):236.1645;Found:236.1649.

[0118] Example 15: Synthesis of quaternary carbon α-amino acid ester 4c catalyzed by chiral pyridoxal catalyst (R)-1a

[0119]

[0120] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3c is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4c (yellow oily liquid, 0.0435 g, yield 87%).

[0121] The ee value of 4c was 99% as determined by HPLC analysis of its benzoyl derivative.

[0122] yellow oil; [α] D 25 = -31.5 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.13-7.04(m,4H),3.07(d,J=13.2Hz,1H),2.73(d,J=13.2Hz,1H),2.31(s,3H),1.60(brs,2H),1.46(s,9H),1.33(s,3H); 13 C NMR (100MHz, CDCl3) δ176.5,136.4,133.8,130.2,129.0,81.2,58.9,46.1,28.1,27.1,21.1; HRMS m / z Calcd.for C 15 H 24 NO2(M+H + ):250.1802;Found:250.1804.

[0123] Example 16: Synthesis of quaternary carbon α-amino acid ester 4d catalyzed by chiral pyridoxal catalyst (R)-1a

[0124]

[0125] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3d is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4d (yellow oily liquid, 0.0693 g, yield 99%).

[0126] The ee value of 4d was 98% as determined by HPLC analysis of its benzoyl derivative.

[0127] yellow oil; [α] D 25 =-25.6 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.77(d,J=7.2Hz,2H),7.73(d,J=8.0Hz,2H),7.57(t,J=7.2Hz,1H),7.47(t,J=7.6Hz,2H) ,7.34(d,J=8.0Hz,2H),3.17(d,J=13.2Hz,1H),2.86(d,J=13.2Hz,1H),1.64(s,2H),1.46(s,9H),1.37(s,3H); 13 C NMR (100MHz, CDCl3) δ196.5,176.1,142.1,137.8,136.2,132.4,130.3,130.13,130.07,128.4,81.5,58.9,46.4,28.1,27.2; HRMS m / z Calcd.for C 21 H 26 NO3(M+H + ):340.1907;Found:340.1911.

[0128] Example 17: Synthesis of quaternary carbon α-amino acid ester 4e catalyzed by chiral pyridoxal catalyst (R)-1a

[0129]

[0130] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3e is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4e (yellow oily liquid, 0.0405 g, yield 78%).

[0131] The ee value of 4e was 99% as determined by HPLC analysis of its benzoyl derivative.

[0132] yellow oil; [α] D 25= -25.3 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.57(d,J=8.4Hz,2H),7.35(d,J=8.0Hz,2H),3.12(d,J= 13.2Hz,1H),2.84(d,J=13.2Hz,1H),1.62(brs,2H),1.44(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ175.8,142.8,132.0,131.2,119.0,110.9,81.8,58.9,46.5,28.1,27.0; HRMS m / z Calcd.for C 15 H 21 N2O2(M+H + ):261.1598;Found:261.1597.

[0133] Example 18: Synthesis of quaternary carbon α-amino acid ester 4f catalyzed by chiral pyridoxal catalyst (R)-1a

[0134]

[0135] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3f is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4f (yellow oily liquid, 0.0635 g, yield 99%).

[0136] The ee value of 4f was 99% as determined by HPLC analysis of its benzoyl derivative.

[0137] yellow oil; [α] D 25 =-20.1 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.85 (d, J=8.4

[0138] Hz,2H),7.44(d,J=8.4Hz,2H),3.16(d,J=13.2Hz,1H),3.04(s,3H),2.87(d,J=13.2Hz,1H),1.62(brs,2H),1.45(s,9H),1.35(s,3H); 13C NMR (100MHz, CDCl3) δ175.9,143.7,139.1,131.4,127.3,81.8,58.8,46.2,44.7,28.1,27.1; HRMS m / z Calcd.forC 15 H 24 NO4S(M+H + ):314.1421;Found:314.1425.

[0139] Example 19: Synthesis of 4 g of quaternary carbon α-amino acid ester catalyzed by chiral pyridoxal catalyst (R)-1a

[0140]

[0141] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3g is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4g (yellow oily liquid, 0.0509 g, yield 85%).

[0142] The ee value of 4g was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 99%.

[0143] yellow oil; [α] D 25 = -16.5 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.22 (d, J=8.4

[0144] Hz,2H),7.03(d,J=8.8Hz,2H),6.48(t,J=74.0Hz,1H),3.08(d,J=13.2Hz,1H),2.75(d,J=13.2Hz,1H),1.55(brs,2H),1.45(s,9H),1.33(s,3H); 13 C NMR (100MHz, CDCl3) δ176.3, 150.3, 134.3, 131.7, 119.4, 116.1 (t, J = 257.7Hz), 81.4, 58.9, 45.7, 28.1, 27.1; 19 FNMR(376MHz, CDCl3)δ-80.6; HRMS m / z Calcd.for C 15 H 22 F2NO3(M+H + ):302.1562;Found:302.1561.

[0145] Example 20: Synthesis of quaternary carbon α-amino acid esters catalyzed by chiral pyridoxal catalyst (R)-1a for 4 h

[0146]

[0147] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3h is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4a (yellow oily liquid, 0.0488 g, yield 73%).

[0148] The ee value of 4h was 98% as determined by HPLC analysis of its benzoyl derivative.

[0149] yellow oil; [α] D 25 = -19.5 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.56 (d, J=8.0Hz, 2H), 7.29 (d, J=8.0Hz, 2H), 3.11 (d, J= 13.2Hz,1H),2.81(d,J=13.2Hz,1H),1.58(brs,2H),1.43(s,9H),1.35(s,3H); 13 C NMR (100MHz, CDCl3) δ176.0, 140.4, 136.2, 131.5, 129.7 (q, J = 306Hz), 128.18, 122.7 (q, J = 2.0Hz), 81.6, 58.9, 46.2, 28.1, 27.1; 19 F NMR(376MHz, CDCl3)δ-42.9; HRMS m / z Calcd.for C 15 H 21 F3NO2S(M+H + ):336.1240;Found:336.1242.

[0150] Example 21: Synthesis of quaternary carbon α-amino acid ester 4i catalyzed by chiral pyridoxal catalyst (R)-1a

[0151]

[0152] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3i is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4i (yellow oily liquid, 0.0586 g, yield 99%).

[0153] The ee value of 4i was 98% as determined by HPLC analysis of its benzoyl derivative.

[0154] yellow oil; [α] D 25 = -11.5 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.94-7.88(m,2H),7.43(d,J=8.0Hz,1H),7.35(t,J=8.0Hz,1H),3.89(s, 3H),3.15(d,J=13.6Hz,1H),2.81(d,J=13.2Hz,1H),1.58(brs,2H),1.46(s,9H),1.35(s,3H); 13 C NMR (100MHz, CDCl3) δ176.2,167.1,137.4,135.0,131.3,130.2,128.4,128.3,81.6,58.9,52.2,46.3,28.1,27.1; HRMS m / z Calcd.for C 16 H 24 NO4(M+H + ):294.1700;Found:294.1701.

[0155] Example 22: Synthesis of quaternary carbon α-amino acid ester 4j catalyzed by chiral pyridoxal catalyst (R)-1a

[0156]

[0157] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3j is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4j (yellow oily liquid, 0.0584 g, yield 86%).

[0158] The ee value of 4j was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 99%.

[0159] yellow oil; [α] D 25 = -14.4 (c = 0.10, CHCl3); 1H NMR (400MHz, CDCl3) δ7.45-7.35(m,4H),7.34-7.29(m,1H),7.19(t,J=8.0Hz,1H),6.90-6.80(m,3H), 5.04(s,2H),3.09(d,J=13.2Hz,1H),2.75(d,J=13.2Hz,1H),1.70(brs,2H),1.47(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ176.3,158.7,138.5,137.2,129.3,128.7,128.0,127.5,123.0,117.1,113.3,81.3,70.0,58.9,46.5,28.1,27.2; HRMS m / z Calcd.for C 21 H 28 NO3(M+H + ):342.2064;Found:342.2064.

[0160] Example 23: Synthesis of quaternary carbon α-amino acid ester 4k catalyzed by chiral pyridoxal catalyst (R)-1a

[0161]

[0162] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3k is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4k (light yellow oily liquid, 0.0641 g, yield 89%).

[0163] The ee value of 4k was 99% when its benzoyl derivative was analyzed by HPLC.

[0164] pale yellow oil; [α] D 25 = -11.9 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.62-7.53(m,2H),7.20(d,J=7.6Hz,1H),7.02(t,J=7.6Hz,1H),3 .05(d,J=13.2Hz,1H),2.70(d,J=13.2Hz,1H),1.65(brs,2H),1.47(s,9H),1.35(s,3H); 13C NMR (100MHz, CDCl3) δ176.1,139.5,139.1,136.0,130.0,129.6,94.4,81.7,58.9,46.0,28.2,27.2; HRMS m / zCalcd.for C 14 H 21 INO2(M+H + ):362.0611;Found:362.0614.

[0165] Example 24: Synthesis of quaternary carbon α-amino acid ester 41 catalyzed by chiral pyridoxal catalyst (R)-1a

[0166]

[0167] The addition amount of each component reagent and the reaction steps are as in Example 8. Compared with Example 8, the only difference is that 3l is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4l (colorless oily liquid, 0.0497 g, yield 92%).

[0168] The ee value of 41 was 98% as determined by HPLC analysis of its benzoylated derivative.

[0169] colorless oil; [α] D 25 = -20.3 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.39-7.34(m,1H),7.33-7.29(m,1H),7.21-7.14(m,2H),3.15(s,2H),1.63(brs,2H),1.46(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ176.2,135.4,135.1,132.1,129.8,128.2,126.6,81.4,59.4,42.5,28.1,26.5; HRMS m / z Calcd.for C 14 H 21 ClNO2(M+H + ):270.1255;Found:270.1256.

[0170] Example 25: Synthesis of quaternary carbon α-amino acid ester 4m catalyzed by chiral pyridoxal catalyst (R)-1a

[0171]

[0172] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3m is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4m (yellow oily liquid, 0.0523 g, yield 83%).

[0173] The ee value of 4m was 98% as determined by HPLC analysis of its benzoyl derivative.

[0174] yellow oil; [α] D 25 = -14.0 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.56 (dd, J=

[0175] 8.0,0.8Hz,1H),7.32(dd,J=7.6,1.6Hz,1H),7.22(td,J=7.2,1.2Hz,1H),7.08 (td,J=7.6,1.6Hz,1H),3.18(s,2H),1.61(brs,2H),1.47(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ176.2,136.9,133.2,131.9,128.4,127.2,126.4,81.4,59.5,44.9,28.1,26.6; HRMS m / z Calcd.for C 14 H 21 BrNO2(M+H + ):314.0750;Found:314.0752.

[0176] Example 26: Synthesis of quaternary carbon α-amino acid ester 4n catalyzed by chiral pyridoxal catalyst (R)-1a

[0177]

[0178] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3n is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4n (yellow oily liquid, 0.0511 g, yield 87%).

[0179] The ee value of 4n was 99% as determined by HPLC analysis of its benzoyl derivative.

[0180] yellow oil; [α] D 25 = -16.9 (c = 0.10, CHCl3);1 H NMR(400MHz, CDCl3)δ6.80-6.74(m,

[0181] 3H),3.85(s,6H),3.11(d,J=13.6Hz,1H),2.73(d,J=13.6Hz,1H),1.98(brs,2H),1.46(s,9H),1.37(s,3H); 13 C NMR (100MHz, CDCl3) δ176.2,148.7,148.1,129.3,122.5,113.6,111.1,81.4,59.1,56.02,56.00,45.8,28.2,27.1; HRMS m / z Calcd.for C 16 H 26 NO4(M+H + ):296.1856;Found:296.1856.

[0182] Example 27: Synthesis of quaternary carbon α-amino acid ester 4o catalyzed by chiral pyridoxal catalyst (R)-1a

[0183]

[0184] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3o is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4o (light yellow oily liquid, 0.0556 g, yield 91%).

[0185] The ee value of 4o was 99% as determined by HPLC analysis of its benzoylated derivative.

[0186] pale yellow oil; [α] D 25 = -23.6 (c = 0.10, CHCl3); 1 H NMR (400 MHz, CDCl3) δ7.35 (d, J

[0187] =5.6Hz,1H),7.33(s,1H),7.07(dd,J=8.4,2.0Hz,1H),3.04(d,J=13.2Hz,1H),2.71(d,J=13.2Hz,1H),1.58(s,2H),1.46(s,9H),1.33(s,3H); 13C NMR (100MHz, CDCl3) δ176.0,137.4,132.24,132.17,131.1,130.2,129.8,81.7,58.9,45.5,28.1,27.1; HRMS m / zCalcd.for C 14 H 20 Cl2NO2(M+H + ):304.0866;Found:304.0868.

[0188] Example 28: Synthesis of quaternary carbon α-amino acid ester 4p catalyzed by chiral pyridoxal catalyst (R)-1a

[0189]

[0190] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3p is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4p (yellow oily liquid, 0.0518 g, yield 91%).

[0191] The ee value of 4p was determined by HPLC analysis of its benzoyl derivative, which was 99%.

[0192] yellow oil; [α] D 25 -21.4 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ6.96 (dd, J=12.4, 2.0Hz, 1H), 6.92 (dd, J=8.8, 2.0Hz, 1H), 6.86 (t, J=8.4Hz, 1H), 3.86(s,3H),3.03(d,J=13.2Hz,1H),2.68(d,J=13.6Hz,1H),1.60(brs,2H),1.46(s,9H),1.32(s,3H); 13 CNMR (100MHz, CDCl3) δ176.3, 152.1 (d, J = 243.9Hz), 146.6 (d, J = 10.6Hz), 130.0 (d, J = 6.1 Hz), 126.0 (d, J = 3.5Hz), 117.9 (d, J = 18.0Hz), 113.2, 81.4, 58.9, 56.4, 45.5, 28.1, 27.0; 19 F NMR(376MHz, CDCl3)δ-135.7; HRMS m / z Calcd.for C 15 H 23 FNO3(M+H+ ):284.1656;Found:284.1659.

[0193] Example 29: Synthesis of quaternary carbon α-amino acid ester 4q catalyzed by chiral pyridoxal catalyst (R)-1a

[0194]

[0195] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3q is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4q (yellow oily liquid, 0.0518 g, yield 90%).

[0196] The ee value of 4q was 99% as determined by HPLC analysis of its benzoyl derivative.

[0197] yellow oil; [α] D 25 = -15.0 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.28 (dd, J=7.2, 2.0Hz, 1H), 7.09 (ddd, J=8.4, 4.8, 2.0Hz, 1H), 7.04 (t, J=8. 8Hz,1H),3.04(d,J=13.2Hz,1H),2.71(d,J=13.2Hz,1H),1.58(brs,2H),1.45(s,9H),1.33(s,3H); 13 C NMR (100MHz, CDCl3) δ176.1, 157.3 (d, J = 246.4Hz), 134.1 (d, J = 4.1Hz), 132.3, 130.0 (d, J = 7 .0Hz), 120.6 (d, J = 17.5Hz), 116.3 (d, J = 20.7Hz), 81.7, 58.9 (d, J = 1.1Hz), 45.4, 28.1, 27.0; 19 F NMR(376MHz, CDCl3)δ-118.6; HRMS m / z Calcd.for C 14 H 20 ClFNO2(M+H + ):288.1161;Found:288.1161.

[0198] Example 30: Synthesis of quaternary carbon α-amino acid ester 4r catalyzed by chiral pyridoxal catalyst (R)-1a

[0199]

[0200] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3r is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4r (yellow oily liquid, 0.0705 g, yield 98%).

[0201] The ee value of 4r was 99% as determined by HPLC analysis of its benzoyl derivative.

[0202] yellow oil; [α] D 25 =-46.3 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.47 (d, J=9.2

[0203] Hz,1H),8.17(d,J=7.6Hz,2H),8.14-8.08(m,2H),8.05(dd,J=10.0,9.2Hz,2H),8.00(t,J=7.6Hz,1H),7.96 (d,J=8.0Hz,1H),3.77(d,J=13.6Hz,1H),3.72(d,J=13.6Hz,1H),1.58(brs,2H),1.48(s,3H),1.46(s,9H); 13 C NMR (100MHz, CDCl3) δ176.6,131.5,131.4,130.9,130.52,130.47,129.2,127.6,127.4 ,127.2,126.0,125.19,125.16,125.0,124.9,124.6,81.4,60.3,42.4,28.1,27.5; HRMS m / z Calcd.for C 24 H 26 NO2(M+H + ):360.1958;Found:360.1959.

[0204] Example 31: Synthesis of quaternary carbon α-amino acid ester 4s catalyzed by chiral pyridoxal catalyst (R)-1a

[0205]

[0206] The addition amount of each component reagent and the reaction steps refer to Example 8, which is different from Example 88 only in that 3s is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4s (yellow oily liquid, 0.0577 g, yield 99%).

[0207] The ee value of 4s was 99% as determined by HPLC analysis of its benzoyl derivative.

[0208] yellow solid; Mp40-41℃; [α] D 25 = -13.1 (c = 0.10, CHCl3); 1 H NMR (400MHz,CDCl3)

[0209] δ7.85-7.73(m,3H),7.69(s,1H),7.49-7.40(m,2H),7.40-7.34(m,1H),3.30(d, J=13.2Hz,1H),2.95(d,J=13.2Hz,1H),1.70(brs,2H),1.47(s,9H),1.40(s,3H); 13 C NMR (100MHz, CDCl3) δ176.4,134.6,133.4,132.5,128.9,128.7,127.8,127.7,126.1,125.6,81.3,59.1,46.6,28.1,27.3; HRMS m / z Calcd.for C 18 H 24 NO2(M+H + ):286.1802;Found:286.1803.

[0210] Example 32: Synthesis of quaternary carbon α-amino acid ester 4t catalyzed by chiral pyridoxal catalyst (R)-1a

[0211]

[0212] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3t is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4t (yellow oily liquid, 0.0386 g, yield 80%).

[0213] The ee value of 4t was 99% as determined by HPLC analysis of its benzoyl derivative.

[0214] yellow oil; [α] D 25 = -36.5 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.24 (dd, J=

[0215] 4.8,2.8Hz,1H),7.05(dd,J=3.2,1.2Hz,1H),6.97(dd,J=5.2,1.2Hz,1H),3.14( d,J=13.6Hz,1H),2.81(d,J=14.0Hz,1H),1.66(s,2H),1.45(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ176.5,137.3,129.5,125.4,123.3,81.3,58.7,40.9,28.1,27.2; HRMS m / z Calcd.for C 12 H 20 NO2S(M+H + ):242.1209;Found:242.1211.

[0216] Example 33: Synthesis of quaternary carbon α-amino acid ester 4u catalyzed by chiral pyridoxal catalyst (R)-1a

[0217]

[0218] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3u is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4u (yellow oily liquid, 0.0275 g, yield 50%).

[0219] The ee value of 4u was 95% as determined by HPLC analysis of its benzoyl derivative.

[0220] yellow oil; [α] D 25 = -7.1 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.73(dd,J=9.2,1.2Hz.1H),7.66(s,1H),7.38(dd,J=9.2,1.2Hz,1H) ,3.16(d,J=13.2Hz,1H),2.90(d,J=13.2Hz,1H),1.64(brs,2H),1.46(s,9H),1.39(s,3H); 13 C NMR (100MHz, CDCl3) δ175.8,149.4,148.6,141.6,135.6,116.2,115.7,82.0,59.0,46.6,28.1,27.1; HRMS m / zCalcd.for C 14 H 20 N3O3(M+H+ ):278.1499;Found:278.1497.

[0221] Example 34: Synthesis of quaternary carbon α-amino acid ester 4v catalyzed by chiral pyridoxal catalyst (R)-1a

[0222]

[0223] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3v is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4v (yellow oily liquid, 0.0478 g, yield 93%).

[0224] The ee value of 4v was 99% as determined by HPLC analysis of its benzoylated derivative.

[0225] yellow oil; [α] D 25 = -25.4 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.35-7.27(m,4H),7.24-7.18(m,1H),6.48(d,J=15.6Hz,1H),6.18-6 .08(m,1H),2.69-2.61(m,1H),2.43-2.35(m,1H),1.70(brs,2H),1.47(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ176.5,137.3,134.1,128.7,127.5,126.3,124.8,81.1,58.2,44.6,28.2,26.6; HRMS m / zCalcd.for C 16 H 24 NO2(M+H + ):262.1802;Found:262.1805.

[0226] Example 35: Synthesis of quaternary carbon α-amino acid ester 4w catalyzed by chiral pyridoxal catalyst (R)-1a

[0227]

[0228] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3w is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4w (yellow oily liquid, 0.0600 g, yield 91%).

[0229] The ee value of 4w was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 99%.

[0230] yellow oil; [α] D 25 = -16.3 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.55(s,1H),7.48(d,J=7.2Hz,1H),7.45(d,J=8.0Hz,1H),7.39(t,J=7.6Hz,1H),6.49(d,J =16.0Hz,1H),6.28-6.18(m,1H),2.67-2.60(m,1H),2.45-2.38(m,1H),1.77(brs,2H),1.46(s,9H),1.34(s,3H); 13 C NMR (100MHz, CDCl3) δ176.3,138.0,132.6,131.1(q,J=31.9Hz),129.4(q,J=1.4Hz),129.1,127 .1,124.0(q,J=3.7Hz),124.2(q,J=270.7Hz),122.9(q,J=3.8Hz),81.3,58.2,44.5,28.1,26.5; 19 F NMR(376MHz, CDCl3)δ-62.8; HRMS m / zCalcd.for C 17 H 23 F3NO2(M+H + ):330.1675;Found:330.1676.

[0231] Example 36: Synthesis of quaternary carbon α-amino acid ester 4x catalyzed by chiral pyridoxal catalyst (R)-1a

[0232]

[0233] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3x is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4x (white solid, 0.0598 g, yield 96%).

[0234] The ee value of 4x was 99% as determined by HPLC analysis of its benzoyl derivative.

[0235] white solid; Mp78-79℃; [α] D 25=-30.0 (c = 0.10, CHCl3); 1 H NMR (400MHz,CDCl3)

[0236] δ7.81-7.74(m,3H),7.68(s,1H),7.56(dd,J=8.8,1.6Hz,1H),7.48-7.39(m,2H),6.64(d,J=15.6Hz,1 H),6.33-6.24(m,1H),2.74-2.67(m,1H),2.51-2.43(m,1H),1.87(brs,2H),1.49(s,9H),1.38(s,3H); 13 C HRMS m / z Calcd.for C 20 H 26 NO2(M+H + ):312.1958;Found:312.1961.

[0237] Example 37: Synthesis of quaternary carbon α-amino acid ester 4y catalyzed by chiral pyridoxal catalyst (R)-1a

[0238]

[0239] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3y is used to replace 3c, and the other conditions are the same as Example 8. Column chromatography gave compound 4y (yellow oily liquid, 0.0427 g, yield 82%).

[0240] The ee value of 4y was 97% as determined by HPLC analysis of its benzoylated derivative.

[0241] yellow oil; [α] D 25 = -44.5 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.41-7.34(m,

[0242] 2H),7.30-7.26(m,3H),2.85(d,J=16.4Hz,1H),2.62(d,J=16.4Hz,1H),1.87(brs,2H),1.49(s,9H),1.39(s,3H); 13 C NMR (100MHz, CDCl3) δ175.5,131.8,128.4,128.0,123.5,85.7,83.4,81.4,58.1,32.2,28.1,26.1; HRMS m / z Calcd.for C 16 H 22 NO2(M+H + ):260.1645;Found:260.1649.

[0243] Example 38: Synthesis of quaternary carbon α-amino acid ester 4z catalyzed by chiral pyridoxal catalyst (R)-1a

[0244]

[0245] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3z is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4z (yellow oily liquid, 0.0626 g, yield 99%).

[0246] The ee value of 4z was determined by HPLC analysis of its benzoyl derivative, which was 98%.

[0247] yellow oil; [α] D 25 =-37.1 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ6.89 (dd, J=

[0248] 8.0,1.2Hz,1H),6.81(d,J=1.6Hz,1H),6.70(d,J=8.4Hz,1H),5.94(s,2H),2.80(d ,J=16.4Hz,1H),2.58(d,J=16.4Hz,1H),1.97(brs,2H),1.47(s,9H),1.37(s,3H); 13 CNMR (100MHz, CDCl3) δ175.5,147.7,147.4,126.2,116.7,111.8,108.4,101.3,83.8,83.1,81.4,58.1,32.1,28.1,26.0; HRMS m / z Calcd.for C 17H 22 NO4(M+H + ):304.1543;Found:304.1546.

[0249] Example 39: Synthesis of quaternary carbon α-amino acid ester 4aa catalyzed by chiral pyridoxal catalyst (R)-1a

[0250]

[0251] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3aa is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4aa (yellow oily liquid, 0.0434 g, yield 82%).

[0252] The ee value of 4aa was determined by HPLC analysis of its benzoyl derivative, which was 99%.

[0253] yellow oil; [α] D 25 =-40.4 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.17 (dd, J=

[0254] 5.2,1.2Hz,1H),7.11(dd,J=3.6,0.8Hz,1H),6.92(dd,J=5.2,3.6Hz,1H),2.85(d ,J=16.8Hz,1H),2.63(d,J=16.4Hz,1H),1.94(brs,2H),1.48(s,9H),1.38(s,3H); 13 CNMR(100MHz, CDCl3)δ175.3,131.6,126.9,126.5,123.5,89.7,81.5,76.4,58.1,32.4,28.1,26.0; HRMS m / z Calcd.for C 14 H 20 NO2S(M+H + ):266.1209;Found:266.1208.

[0255] Example 40: Synthesis of quaternary carbon α-amino acid ester 4ab catalyzed by chiral pyridoxal catalyst (R)-1a

[0256]

[0257] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3ab is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4ab (brown oily liquid, 0.0323 g, yield 64%).

[0258] The ee value of 4ab was determined by HPLC analysis of its benzoyl derivative, which was 96%.

[0259] brown oil; [α] D 25 = -25.0 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ2.57 (dt, J=

[0260] 16.4,2.4Hz,1H),2.33(dt,J=16.0,2.4Hz,1H),2.11(tt,J=6.8,2.4Hz,2H), 1.88(brs,2H),1.49-1.41(m,11H),1.36-1.23(m,7H),0.87(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ175.7,83.5,81.1,75.5,58.0,31.5,31.1,28.7,28.0,25.9,22.3,18.8,14.1; HRMS m / z Calcd.for C 15 H 28 NO2(M+H + ):254.2115;Found:254.2114.

[0261] Example 41: Synthesis of quaternary carbon α-amino acid ester 4ac catalyzed by chiral pyridoxal catalyst (R)-1a

[0262]

[0263] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3ac is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4ac (yellow oily liquid, 0.0376 g, yield 72%).

[0264] The ee value of 4ac was 95% as determined by HPLC analysis of its benzoylated derivative.

[0265] yellow oil; [α] D 25 = -22.0 (c = 0.10, CHCl3);1 H NMR (400MHz, CDCl3) δ3.62 (t, J=6.4

[0266] Hz,2H),2.62-2.53(m,1H),2.40-2.30(m,3H),2.00-1.85(m,4H),1.45(s,9H),1.30(s,3H); 13 C NMR (100MHz, CDCl3) δ175.6,81.29,81.27,76.8,57.9,43.8,31.6,31.4,28.0,25.9,16.2; HRMS m / z Calcd.for C 13 H 23 ClNO2(M+H + ):260.1412;Found:260.1413.

[0267] Example 42: Synthesis of quaternary carbon α-amino acid ester 4ad catalyzed by chiral pyridoxal catalyst (R)-1a

[0268]

[0269] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 3ad is used to replace 3a, and the other conditions are the same as Example 8. Column chromatography gave compound 4ad (yellow oily liquid, 0.0365 g, yield 69%).

[0270] The ee value of 4ad was 96% as determined by HPLC analysis of its benzoyl derivative.

[0271] yellow oil; [α] D 25 = -38.6 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ6.02-5.96(m,

[0272] 1H),2.71(d,J=16.4Hz,1H),2.48(d,J=16.0Hz,1H),2.10-2.00(m,4H),1.86(brs,2H),1.63-1.49(m,4H),1.46(s,9H),1.31(s,3H); 13C NMR (100MHz, CDCl3) δ175.6,134.1,120.7,85.2,82.4,81.2,58.0,32.1,29.5,28.0,25.9,25.6,22.4,21.6; HRMS m / zCalcd.for C 16 H 26 NO2(M+H + ):264.1958;Found:264.1958.

[0273] Example 43: Synthesis of quaternary carbon α-amino acid ester 4ae catalyzed by chiral pyridoxal catalyst (R)-1a

[0274]

[0275] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2b is used to replace 2a and 3s is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ae (yellow oily liquid, 0.0517 g, yield 83%).

[0276] The ee value of 4ae was 96% as determined by HPLC analysis of its benzoyl derivative.

[0277] yellow oil; [α] D 25 = -33.4 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.83-7.74(m,

[0278] 3H),7.70(s,1H),7.49-7.42(m,2H),7.37(dd,J=8.4,1.6Hz,1H),3.35(d,J=13.2Hz,1H),2.92(d,J=13.2H z,1H),1.97-1.85(m,3H),1.68-1.57(m,1H),1.49-1.44(m,10H),1.31-1.12(m,1H),0.96(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ175.7,134.3,133.5,132.6,129.0,128.7,127.9,127.7,126.1,125.7,81.6,62.5,45.9,43.2,28.2,17.4,14.6; HRMS m / z Calcd.for C 20 H 28 NO2(M+H +):314.2115;Found:314.2115.

[0279] Example 44: Synthesis of quaternary carbon α-amino acid ester 4af catalyzed by chiral pyridoxal catalyst (R)-1a

[0280]

[0281] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2c is used to replace 2a and 3s is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4af (yellow oily liquid, 0.0515 g, yield 79%).

[0282] The ee value of 4af was 97% as determined by HPLC analysis of its benzoyl derivative.

[0283] yellow oil; [α] D 25 =-30.0 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.84-7.73(m,

[0284] 3H),7.69(s,1H),7.49-7.41(m,2H),7.36(dd,J=8.4,1.2Hz,1H),3.35(d,J=13.2Hz,1H),2.90(d,J=13.2Hz,1H) ,1.99-1.86(m,1H),1.67-1.56(m,3H),1.48(s,9H),1.44-1.29(m,3H),1.23-1.13(m,1H),0.93(t,J=7.2Hz,3H); 13 C NMR (100MHz,CDCl3)δ 13 CNMR (100MHz, CDCl3) δ176.0,134.5,133.4,132.5,129.0,128.7,127.9,127.7,126.1,125.7,81.4,62.3,46.1,40.8,28.2,26.2,23.2,14.1; HRMS m / z Calcd.for C 21 H 30 NO2(M+H + ):328.2271;Found:328.2273.

[0285] Example 45: Synthesis of quaternary carbon α-amino acid ester 4ag catalyzed by chiral pyridoxal catalyst (R)-1a

[0286]

[0287] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2d is used to replace 2a and 3s is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ag (yellow oily liquid, 0.0523 g, yield 77%).

[0288] The ee value of 4ag was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 94%.

[0289] yellow oil; [α] D 25 = -27.9 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.84-7.73(m,

[0290] 3H),7.69(s,1H),7.48-7.41(m,2H),7.38-7.34(m,1H),3.35(d,J=13.2Hz,1H),2.90(d,J=13.2Hz,1H ),1.96-1.87(m,1H),1.71-1.57(m,3H),1.51-1.45(m,10H),1.44-1.14(m,5H),0.90(t,J=6.8Hz,3H); 13 C NMR (100MHz,CDCl3)δ 13 C NMR (100MHz, CDCl3) δ175.9,134.4,133.5,132.5,129.0,128.7,127.9,127 .7,126.1,125.7,81.4,62.4,46.0,41.1,32.3,28.3,23.7,22.6,14.1; HRMS m / z Calcd.for C 22 H 32 NO2(M+H + ):342.2428;Found:342.2429.

[0291] Example 46: Synthesis of quaternary carbon α-amino acid ester 4ah catalyzed by chiral pyridoxal catalyst (R)-1a

[0292]

[0293] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that 2e is used to replace 2a and 3s is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ah (yellow solid, 0.0608 g, yield 88%).

[0294] The ee value of 4ah was 99% as determined by HPLC analysis of its benzoylated derivative.

[0295] yellow solid; Mp63-64℃; [α] D 25 = -20.5 (c = 0.10, CHCl3); 1 H NMR (400MHz,CDCl3)

[0296] δ7.86-7.71(m,3H),7.68(s,1H),7.49-7.39(m,2H),7.35(dd,J=8.4,1.2Hz,1H),4.65(dd,J=9.2,6.4Hz,2H),3.97(d,J=8 .8Hz,1H),3.54(d,J=8.8Hz,1H),3.38(s,3H),3.24(d,J=13.2Hz,1H),2.91(d,J=13.2Hz,1H),1.89(brs,2H),1.46(s,9H); 13 C HRMS m / z Calcd.for C 20 H 28 NO4(M+H + ):346.2013;Found:346.2015.

[0297] Example 47: Synthesis of quaternary carbon α-amino acid ester 4ai catalyzed by chiral pyridoxal catalyst (R)-1a

[0298]

[0299] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2f is used to replace 2a and 3s is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ai (yellow oily liquid, 0.0636 g, yield 92%).

[0300] The ee value of 4ai was 99% as determined by HPLC analysis of its benzoyl derivative.

[0301] yellow oil; [α] D 25 = -12.0 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.84-7.72(m,

[0302] 3H),7.68(s,1H),7.50-7.41(m,2H),7.35(dd,J=8.4,1.6Hz,1H),3.33(d,J=13.2Hz,1H),2.94(d,J=13.2Hz,1H),2.61(td,J=1 2.4,5.2Hz,1H),2.44(td,J=12.4,4.4Hz,1H),2.28-2.17(m,1H),2.13(s,3H),1.99-1.87(m,1H),1.69(brs,2H),1.48(s,9H).; 13 C HRMS m / z Calcd.forC 20 H 28 NO2S(M+H + ):346.1835;Found:346.1832.

[0303] Example 48: Synthesis of quaternary carbon α-amino acid ester 4aj catalyzed by chiral pyridoxal catalyst (R)-1a

[0304]

[0305] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2g is used to replace 2a and 3s is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4aj (yellow oily liquid, 0.0669 g, yield 84%).

[0306] The ee value of 4aj was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 94%.

[0307] yellow oil; [α] D 25= -25.9 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.85-7.73(m,3H),7.67(s,1H),7.49-7.40(m,2H),7.35(dd,J=8.4,1.6Hz,1H),3.33(d,J=13.2Hz,1H) ,2.92(d,J=13.2Hz,1H),2.45-2.34(m,1H),2.27-2.13(m,2H),2.00-1.89(m,1H),1.56(brs,2H),1.47(s,9H),1.45(s,9H); 13 C NMR (100MHz, CDCl3) δ175.3,172.8,134.0,133.4,132.6,129.0,128.6,128.0,127 .74,127.72,126.2,125.8,81.8,80.5,61.8,45.7,35.7,30.6,28.23,28.21; HRMS m / z Calcd.for C 24 H 34 NO4(M+H + ):400.2482;Found:400.2487.

[0308] Example 49: Synthesis of quaternary carbon α-amino acid ester 4ak catalyzed by chiral pyridoxal catalyst (R)-1a

[0309]

[0310] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2b is used to replace 2a and 3v is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ak (colorless oily liquid, 0.0442 g, yield 76%).

[0311] The ee value of 4ak was determined by HPLC analysis of its benzoyl derivative, which was 96%.

[0312] colorless oil; [α] D 25 = -27.3 (c = 0.10, CHCl3); 1H NMR (400MHz, CDCl3) δ7.35-7.26(m,4H),7.24-7.18(m,1H),6.48(d,J=16.0Hz,1H),6.18-6.06(m,1H),2.79-2.63(m,1H),2.42 -2.32(m,1H),1.80-1.62(m,3H),1.58-1.49(m,1H),1.47(s,9H),1.46-1.33(m,1H),1.29-1.15(m,1H),0.93(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ176.1,137.3,134.2,128.6,127.4,126.3,124.7,81.1,61.4,43.9,42.6,28.2,17.4,14.6; HRMS m / zCalcd.for C 18 H 28 NO2(M+H + ):290.2115;Found:290.2122

[0313] Example 50: Synthesis of quaternary carbon α-amino acid ester 4a1 catalyzed by chiral pyridoxal catalyst (R)-1a

[0314]

[0315] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that 2c is used to replace 2a and 3v is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4a1 (yellow oily liquid, 0.0532 g, yield 88%).

[0316] The ee value of 4al was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 99%.

[0317] yellow oil; [α] D 25 = -31.3 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.35-7.26(m,

[0318] 4H),7.23-7.17(m,1H),6.48(d,J=16.0Hz,1H),6.17-6.06(m,1H),2.73-2.62(m,1H),2.41-2.30(m,1H),1.8 9-1.70(m,3H),1.60-1.50(m,1H),1.47(s,9H),1.42-1.26(m,3H),1.21-1.08(m,1H),0.90(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ176.0,137.3,134.2,128.6,127.4,126.3,124.6,81.1,61.3,43.9,39.9,28.2,26.2,23.1,14.1; HRMS m / z Calcd.for C 19 H 30 NO2(M+H + ):304.2271;Found:304.2271.

[0319] Example 51: Synthesis of quaternary carbon α-amino acid ester 4am catalyzed by chiral pyridoxal catalyst (R)-1a

[0320]

[0321] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2d is used to replace 2a and 3v is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4am (yellow oily liquid, 0.0598 g, yield 94%).

[0322] The ee value of 4am was determined by HPLC analysis of its benzoyl derivative, which was 98%.

[0323] yellow oil; [α] D 25 = -19.9 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.35-7.26(m,

[0324] 4H),7.23-7.17(m,1H),6.48(d,J=15.6Hz,1H),6.17-6.08(m,1H),2.72-2.63(m,1H),2.41-2.32(m ,1H),1.82-1.72(m,3H),1.58-1.50(m,1H),1.50(s,9H),1.43-1.11(m,6H),0.89(t,J=6.8Hz,3H);13 C NMR (100MHz, CDCl3) δ176.1,137.3,134.2,128.6,127.4,126.3,124.7,81.1,61.4,43.9,40.3,32.2,28.2,23.6,22.6,14.1; HRMS m / z Calcd.forC 20 H 32 NO2(M+H + ):318.2428;Found:318.2429.

[0325] Example 52: Synthesis of quaternary carbon α-amino acid ester 4an catalyzed by chiral pyridoxal catalyst (R)-1a

[0326]

[0327] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2e is used to replace 2a and 3v is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4an (yellow oily liquid, 0.0600 g, yield 93%).

[0328] The ee value of 4an was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 99%.

[0329] yellow oil; [α] D 25 = -15.1 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.34-7.26(m,

[0330] 4H),7.24-7.17(m,1H),6.49(d,J=16.0Hz,1H),6.14-6.04(m,1H),4.63(s,2H),3.86(d,J=8.8Hz,1H),3.48(d,J= 8.8Hz,1H),3.36(s,3H),2.60(dd,J=13.2,6.8Hz,1H),2.38(dd,J=13.6,8.4Hz,1H),1.98(brs,2H),1.47(s,9H); 13 C NMR (100MHz, CDCl3) δ174.4,137.1,134.5,128.6,127.5,126.3,123.3,96.9,81.5,74.1,61.9,55.4,40.3,28.2; HRMSm / z Calcd.for C 18 H 28NO4(M+H + ):322.2013;Found:322.2013.

[0331] Example 53: Synthesis of quaternary carbon α-amino acid ester 4ao catalyzed by chiral pyridoxal catalyst (R)-1a

[0332]

[0333] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2f is used to replace 2a and 3v is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ao (yellow oily liquid, 0.0332 g, yield 52%).

[0334] The ee value of 4ao was 98% as determined by HPLC analysis of its benzoyl derivative.

[0335] yellow oil; [α] D 25 = -18.1 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.35-7.27(m,

[0336] 4H),7.24-7.19(m,1H),6.49(d,J=15.6Hz,1H),6.14-6.04(m,1H),2.73-2.64(m,1H),2.64-2.54(m,1 H),2.47-2.36(m,2H),2.11(s,3H),2.10-2.04(m,1H),1.91-1.81(m,1H),1.71(brs,2H),1.48(s,9H); 13 C NMR (100MHz, CDCl3) δ175.3,137.1,134.6,128.7,127.6,126.3,123.9,81.6,61.2,43.9,39.7,28.9,28.2,15.7; HRMS m / z Calcd.forC 18 H 28 NO2S(M+H + ):322.1835;Found:322.1840.

[0337] Example 54: Synthesis of quaternary carbon α-amino acid ester 4ap catalyzed by chiral pyridoxal catalyst (R)-1a

[0338]

[0339] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that 2b is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ap (yellow oily liquid, 0.0470 g, yield 82%).

[0340] The ee value of 4ap was obtained by HPLC analysis of its benzoyl derivative, and its ee value was 98%.

[0341] yellow oil; [α] D 25 = -41.4 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.40-7.33(m,

[0342] 2H),7.29-7.24(m,3H),2.86(d,J=16.4Hz,1H),2.59(d,J=16.4Hz,1H),1.86(brs,2H),1.79-1.69( m,1H),1.62-1.53(m,1H),1.48(s,9H),1.46-1.35(m,1H),1.31-1.17(m,1H),0.93(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ175.1,131.7,128.3,128.0,123.5,85.5,83.3,81.4,61.2,42.0,31.3,28.1,17.5,14.5; HRMS m / z Calcd.for C 18 H 26 NO2(M+H + ):288.1958;Found:288.1962.

[0343] Example 55: Synthesis of quaternary carbon α-amino acid ester 4aq catalyzed by chiral pyridoxal catalyst (R)-1a

[0344]

[0345] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2c is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4aq (yellow oily liquid, 0.0458 g, yield 76%).

[0346] The ee value of 4aq was 97% as determined by HPLC analysis of its benzoylated derivative.

[0347] yellow oil; [α] D 25 = -52.0 (c = 0.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.40-7.34(m,2H),7.30-7.23(m,3H),2.86(d,J=16.4Hz,1H),2.60(d,J=16.4Hz,1H),1.89(brs ,2H),1.82-1.72(m,1H),1.66-1.54(m,1H),1.49(s,9H),1.44-1.28(m,3H),1.24-1.11(m,1H),0.91(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ175.1,131.7,128.3,128.0,123.5,85.5,83.3,81.3,61.2,39.4,31.3,28.1,26.3,23.0,14.1; HRMS m / z Calcd.for C 19 H 28 NO2(M+H + ):302.2115;Found:302.2116.

[0348] Example 56: Synthesis of quaternary carbon α-amino acid ester 4ar catalyzed by chiral pyridoxal catalyst (R)-1a

[0349]

[0350] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that 2d is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4ar (yellow oily liquid, 0.0474 g, yield 75%).

[0351] The ee value of 4ar was determined by HPLC analysis of its benzoyl derivative, which was 97%.

[0352] yellow oil; [α] D 25 = -33.8 (c = 0.10, CHCl3); 1H NMR (400MHz, CDCl3) δ7.39-7.32(m,2H),7.28-7.23(m,3H),2.84(d,J=16.4Hz,1H),2.59(d,J=16.4Hz,1H), 1.94(brs,2H),1.80-1.69(m,1H),1.64-1.53(m,1H),1.47(s,9H),1.42-1.12(m,6H),0.87(t,J=6.8Hz,3H); 13 C NMR (100MHz, CDCl3) δ175.0,131.7,128.3,127.9,123.5,85.5,83.3,81.3,61.2,39.6,32.1,31.2,28.1,23.8,22.5,14.0; HRMS m / z Calcd.for C 20 H 30 NO2(M+H + ):316.2271;Found:316.2272.

[0353] Example 57: Synthesis of quaternary carbon α-amino acid ester 4as catalyzed by chiral pyridoxal catalyst (R)-1a

[0354]

[0355] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2h is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4as (yellow oily liquid, 0.0475 g, yield 72%).

[0356] The ee value of 4as was 95% as determined by HPLC analysis of its benzoyl derivative.

[0357] yellow oil; [α] D 25 = -27.1 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.40-7.34(m,

[0358] 2H),7.30-7.25(m,3H),2.85(d,J=16.4Hz,1H),2.59(d,J=16.4Hz,1H),1.87-1.71 (m,3H),1.63-1.53(m,1H),1.48(s,9H),1.45-1.10(m,8H),0.88(t,J=6.4Hz,3H); 13CNMR(100MHz, CDCl3)δ175.1,131.8,128.3,128.0,123.5,85.6,83.4,81.4,61.2,39.7,31.7,31.3,29.6,28.1,24.1,22.7,14.2; HRMS m / z Calcd.for C 21 H 32 NO2(M+H + ):330.2428;Found:330.2431.

[0359] Example 58: Synthesis of quaternary carbon α-amino acid ester 4at catalyzed by chiral pyridoxal catalyst (R)-1a

[0360]

[0361] The addition amount of each component reagent and the reaction steps are as shown in Example 8. Compared with Example 8, the only difference is that 2e is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4at (yellow oily liquid, 0.0374 g, yield 58%).

[0362] The ee value of 4at was 87% as determined by HPLC analysis of its benzoyl derivative.

[0363] yellow oil; [α] D 25 = -16.4 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.39-7.35(m,

[0364] 2H),7.30-7.26(m,3H),4.65(s,2H),3.84(d,J=8.8Hz,1H),3.55(d,J=8.8Hz,1H),3.3 7(s,3H),2.82(d,J=16.4Hz,1H),2.65(d,J=16.0Hz,1H),1.95(brs,2H),1.49(s,9H); 13 C NMR (100MHz, CDCl3) δ173.3,131.8,128.4,128.1,123.4,96.9,84.3,83.7,81.8,73.2,61.5,55.5,28.13,28.11; HRMS m / z Calcd.for C 18 H 26 NO4(M+H + ):320.1856;Found:320.1861.

[0365] Example 59: Synthesis of quaternary carbon α-amino acid ester 4au catalyzed by chiral pyridoxal catalyst (R)-1a

[0366]

[0367] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2f is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4au (yellow oily liquid, 0.0502 g, yield 78%).

[0368] The ee value of 4au was 98% as determined by HPLC analysis of its benzoyl derivative.

[0369] yellow oil; [α] D 25 =-47.9 (c=0.10, CHCl3); H NMR (400MHz, CDCl3) δ7.41-7.31 (m,

[0370] 2H),7.30-7.23(m,3H),2.85(d,J=16.4Hz,1H),2.69-2.54(m,2H),2.48-2. 38(m,1H),2.11(s,3H),2.09-2.03(m,1H),1.97-1.86(m,3H),1.49(s,9H); 13 C NMR (100MHz, CDCl3) δ174.2,131.7,128.4,128.1,123.3,84.8,83.8,81.9,61.0,39.0,31.4,29.0,28.1,15.7; HRMS m / z Calcd.for C 18 H 26 NO2S(M+H + ):320.1679;Found:320.1683.

[0371] Example 60: Synthesis of quaternary carbon α-amino acid ester 4av catalyzed by chiral pyridoxal catalyst (R)-1a

[0372]

[0373] The addition amount of each component reagent and the reaction steps refer to Example 8. Compared with Example 8, the only difference is that 2g is used to replace 2a and 3y is used to replace 3a. The other conditions are the same as Example 8. Column chromatography gave compound 4av (brown oily liquid, 0.0371 g, yield 50%).

[0374] The ee value of 4av was 90% as determined by HPLC analysis of its benzoyl derivative.

[0375] brown oil; [α] D 25 = -22.0 (c = 0.10, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.39-7.33(m,

[0376] 2H),7.29-7.24(m,3H),2.86(d,J=16.4Hz,1H),2.62(d,J=16.4Hz,1H),2.42-2.32(m,1H),2.2 7-2.16(m,1H),2.10-2.00(m,1H),1.98-1.91(m,1H),1.88(brs,2H),1.49(s,9H),1.44(s,9H); 13 C NMR (100MHz, CDCl3) δ174.4,172.6,131.8,128.4,128.2,123.4,85.0,83.7,81.9,80.6,60.7,34.2,31.1,30.6,28.2,28.1; HRMS m / z Calcd.for C 22 H 32 NO4(M+H + ):374.2326;Found:374.2329.

[0377] The above description of the embodiments is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A biaryl chiral N-quaternary ammonium salt pyridoxal catalyst, characterized in that: Its chemical structure is as follows: Among them, R 1 , R 2 is hydrogen, or a substituted or unsubstituted group of: C1~C 24 Hydrocarbon, C3~C 30 Cycloalkyl or aryl, C1~C 24 The carbonyl group, C1~C 24 sulfonyl or phosphoryl; R 3 , R 4 , R 5 is hydrogen or C 1-24 X1, X2, X3 and X4 are independently N or CR, R is H or C 1-24 X5 is a fluoride ion, a chloride ion, a bromide ion, an iodide ion, a tetrafluoroborate anion, a trifluoroacetate anion, a trifluoromethanesulfonate anion, a methanesulfonate anion, a p-toluenesulfonate anion, a nitrate anion, or a cyanide anion.

2. A biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 1, characterized in that: The hydrocarbon group is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, 2-biphenyl, 3-biphenyl, 4-biphenyl, 2,6-biphenyl, 3,5-biphenyl, (1-phenyl)ethyl, 1-naphthyl, 2-naphthyl; R 1 , R 2 The substituted groups are substituted by the following substituents: halogen, C1-C8 hydrocarbon, C3-C 12 a cycloalkyl or aryl group, a C1-C8 carbonyl group, a C1-C8 sulfonyl or phosphoryl group, a C1-C8 alkoxy group or an amine group, wherein the carbonyl group refers to an aldehyde group, a ketocarbonyl group, an ester carbonyl group, a carboxyl group or an amide group.

3. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst as claimed in claim 1 or 2, characterized in that: The following steps are involved: (1) Compound 5 was used as a raw material to obtain compound 6 by aldehyde protection; (2) Compound 6 is coupled with compound 7 to obtain compound 8; (3) Compound 8 is treated with an oxidant to obtain a carboxylic acid compound 9, which is then resolved with (S)-BINOL to obtain two configurations of compound 10; (4) Compound 10 with a single configuration is subjected to the removal of BINOL under the action of a base and then acidified to obtain a chiral acid compound 9 with a single configuration; (5) The chiral acid compound 9 of a single configuration is condensed with the amine 11 to generate compound 12; (6) Compound 12 is first N-alkylated with pyridine and then hydrolyzed under the action of an acid to obtain the final pyridoxal catalyst 1, which is the target product; The general chemical structure formula of compound 5 is: The general chemical structure formula of compound 6 is: The general chemical structure formula of compound 7 is: The general chemical structure formula of compound 8 is: The chemical structural formulas of carboxylic acid compound 9 and chiral acid compound 9 are respectively: The general chemical structure formula of compound 10 is: The general chemical structure of amine 11 is: The general chemical structure of compound 12 is:

4. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 3, characterized in that: The specific process of step (1) is as follows: Compound 5 is used to protect the aldehyde group to obtain compound 6, wherein the molar ratio of compound 5 to the compound providing the protective group is 1:1 to 1:100, the reaction temperature is 0°C to 100°C, and the reaction time is 1 to 24 hours.

5. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 3, characterized in that: The specific process of step (2) is as follows: Add compound 6, compound 7, palladium complex, ligand and base to a reaction bottle, and then inject solvent under an inert gas protective atmosphere. After reaction, the coupling product compound 8 can be obtained, wherein the molar ratio of compound 6 to compound 7 is 1:1 to 1:5, the reaction temperature is -20°C to 120°C, and the reaction time is 1 to 24h.

6. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 3, characterized in that: The specific process of step (3) is as follows: In an organic solvent, compound 8 reacts with an oxidant to obtain carboxylic acid compound 9, wherein the molar ratio of compound 8 to the oxidant is 1:1 to 1:20, the reaction temperature is -20°C to 50°C, and the reaction time is 1 to 72 hours.

7. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 3, characterized in that: The specific process of step (4) is as follows: Add carboxylic acid compound 9, (S)-BINOL, condensing agent and base into a reaction container, then add solvent, and react to obtain two configurations of compound 10, wherein the molar ratio of carboxylic acid compound 9 to condensing agent is 1:1 to 1:5, the reaction temperature is -20°C to 50°C, and the reaction time is 1 to 48h; In an organic solvent, compound 10 reacts with a base and then undergoes acidification to obtain chiral acid compound 9, wherein the molar ratio of compound 10 to the base is 1:1 to 1:10, the reaction temperature is -20°C to 120°C, and the reaction time is 1 to 72 hours.

8. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 3, characterized in that: The specific process of step (5) is as follows: Chiral acid compound 9 and amine 11 are reacted with a condensing agent to obtain compound 12, wherein the molar ratio of chiral acid compound 9 to amine 11 is 1:1 to 1:5, the reaction temperature is 0°C to 100°C, and the reaction time is 1 to 24 hours.

9. The method for preparing a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst according to claim 3, characterized in that: The specific process of step (6) is as follows: Compound 12 is first reacted with an alkylating agent to obtain an N-alkylated intermediate, and then reacted with an acid to obtain pyridoxal catalyst 1, wherein the molar ratio of compound 11 to the alkylating agent is 1:1 to 1:100, the reaction temperature is 0°C to 100°C, and the reaction time is 1 to 48 hours.

10. Use of a biaryl chiral N-quaternary ammonium salt pyridoxal catalyst as claimed in claim 1 or 2, characterized in that: The catalyst is used for the asymmetric nucleophilic substitution reaction of unprotected α-amino acids on halogenated alkanes and for the synthesis of a series of non-natural quaternary carbon α-amino acid derivatives with high stereoselectivity.

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