A method for the palladium-catalyzed asymmetric hydrogenolysis synthesis of chiral n-(1,2-diphenylethyl)-4-methylbenzenesulfonamides

Abstract

The application discloses a method for synthesizing chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide by using palladium and a chiral biphosphine ligand as a catalytic system, borohydride as a hydrogen source, and cis-2,3-diphenyl-1-toluenesulfonyl aziridine derivatives as a substrate, and assembles chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivatives by asymmetric hydrogenolysis. The method is simple and practical, raw materials are easy to obtain, has high enantioselectivity, good yield, simple operation, and the like, and has the advantages of commercially available catalysts.

Description

Technical Field

[0001] This invention relates to a method for synthesizing chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivatives by palladium-catalyzed asymmetric hydrogenolysis of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivatives. Background Technology

[0002] Amines are among the most valuable compounds in chemical synthesis, widely found in natural products, fine chemicals, pharmaceuticals, and agrochemicals. The β-phenylethylamine group forms the structural basis for many small molecules with unique and often biologically active components. This structural framework is widely present in many important neurotransmitters and is extensively used in the synthesis of drug targets for treating depression and anxiety disorders, Parkinson's disease, and Alzheimer's disease. (Reference 1: (a) Gallardo-Godoy, A.; Fierro, A.; McLean, TH; Castillo, M.; Cassels, BK; Reyes-Parada, M.; Nichols, DEJ Med. Chem. 2005, 48, 2407. (b) Shimazu, S.; Miklya, I. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2004, 28, 421.)

[0003] One method for constructing β-phenylethylamine compounds is through ring-opening of phenyl-substituted azacyclic propanes. Currently, there is considerable research on the metal-catalyzed ring-opening construction of chiral β-phenylethylamine compounds from azacyclic propanes, but the chiral center is generally located at the β-position, and the azacyclic propanes used are mostly monosubstituted. (Reference 2: (a) Hu, X.; Cheng-Sánchez, I.; Cuesta-Galisteo, S.; Nevado, CJAm. Chem. Soc. 2023, 145, 6270. (b) Liu, S.; Wang, S.-L.; Wan, J.; Peng, S.; Zhang, J.-R.; Ding, H.-J.; Zhang, B.; Ni, H.-L.; Cao, P.; Hu, P.; Wang, B.-Q.; Chen, B. Org. L.) ett. 2023, 25, 6582. (c) Lan, Y.;Han, Q.;Liao, P.;Chen, R.;Fan, F.;Zhao, X.;Liu, WJAm.Chem.Soc. 2024, 146, 25426. (d) Huang, C.-Y.;Doyle, AGChem.Rev. 2014, 114, 8153.) Therefore, developing a method for the efficient construction of β-phenylethylamine compounds with chiral centers at the α-position via metal-catalyzed ring-opening of nitrogen-containing heterocyclic propanes is of great value. Summary of the Invention

[0004] The purpose of this invention is to provide a palladium-catalyzed asymmetric hydrogenolysis method for synthesizing chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivatives from cis-2,3-diphenyl-1-toluenesulfonylaziridine derivatives. This method has the advantages of being simple and practical to operate, having readily available raw materials, high enantioselectivity, good yield, and readily available catalysts.

[0005] To achieve the above objectives, the technical solution of the present invention is as follows:

[0006] A palladium-catalyzed asymmetric hydrogenolysis of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative to synthesize a chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative is disclosed. The method uses palladium and a chiral bisphosphine ligand as the catalytic system, cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1 as the substrate, and borohydride as the hydrogen source to synthesize chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative 2 via asymmetric hydrogenolysis.

[0007] The reaction formula is as follows:

[0008]

[0009] In the formula:

[0010] Ar is a benzene ring, an aromatic heterocycle (e.g., an aromatic heterocycle containing nitrogen, oxygen, and sulfur atoms), or a benzene ring containing a substituent, wherein the substituent is one of C1-C20 alkyl, aryl (e.g., a benzene ring), fluorine, or chlorine;

[0011] The catalyst is a complex of a palladium precursor and a bisphosphine ligand.

[0012] As used herein, the term "C1-C20 alkyl" refers to a straight-chain or branched alkyl group having 1-20 carbon atoms; preferably "C1-C3 alkyl", including methyl and ethyl.

[0013] As used in this article, the term "heteroaryl" refers to an aromatic heterocycle that contains one or more (e.g., 1-3) heteroatoms (e.g., nitrogen, oxygen, sulfur) in addition to a carbon atom, examples of which include 5-benzofuranyl, etc.

[0014] Based on the above technical solutions, preferably, the borohydride is one of lithium borohydride, sodium borohydride (NaBH4), potassium borohydride, pinacol borane (HBpin), or catechol borane (CatBH), with pinacol borane being the most preferred.

[0015] Based on the above technical solutions, preferably, the molar ratio of borohydride and cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative is 1.2:1 to 2.0:1, and more preferably 1.5:1.

[0016] Based on the above technical solution, preferably, the reaction solvent is an organic solvent, namely tetrahydrofuran (THF), 2-methyltetrahydrofuran, 1,2-dichloroethane, ethylene glycol dimethyl ether (DME), ethyl acetate (EtOAc), N,N-dimethylformamide (DMF), toluene (PhMe), 1,4-dioxane, isopropanol (… i One or more of PrOH, preferably tetrahydrofuran (THF).

[0017] Based on the above technical solutions, preferably, the reaction temperature is 30-40℃; the reaction time is 8-72 hours, preferably 24-72 hours, and more preferably 36-72 hours.

[0018] Based on the above technical solution, preferably, the molar ratio of the palladium precursor and the cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative is 0.05:1 to 0.1:1, and more preferably 0.05:1.

[0019] Based on the above technical solution, preferably, the molar ratio of the chiral bisphosphine ligand and the cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative is 0.06:1 to 0.15:1, and more preferably 0.06:1.

[0020] Based on the above technical solution, preferably, the amount of organic solvent used is 0.5 to 5 ml per 0.3 mmol of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative, preferably 3 ml; the organic solvent is added in two parts, the first part is added during the preparation of the catalyst, and the second part is added during the synthesis of the product, and the volume ratio of the first added solvent to the second added organic solvent is 1:1.

[0021] Preferably, in the above technical solution, the method further includes a molecular sieve, wherein the molecular sieve is... or Molecular sieves are used at a dosage of 50-150 mg per 0.2-0.3 mmol of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative, preferably per 0.1 mmol of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative. 50 mg of molecular sieve.

[0022] Based on the above technical solutions, preferably, the palladium precursor is palladium acetate (Pd(OAc)2), palladium trifluoroacetate (Pd(CF3OCO)2), bis(acetylacetone)palladium (Pd(acac)2), bis(dibenzylacetone)palladium (Pd(dba)2), bis(acetonitrile)palladium chloride (Pd(MeCN)2Cl2), or bis(tri-tert-butylphosphine)palladium (Pd(P... t Bu3)2) or di(cyanobenzene)palladium dichloride (Pd(PhCN)2Cl2), preferably palladium acetate (Pd(OAc)2).

[0023] Based on the above technical solutions, preferably, the chiral bisphosphine ligand is (S)-SegPhos, (R)-PhanePhos, (S,S)-ChiraPhos, (S)-DM-SegPhos, (S)-DTBM-SegPhos, (S)-SynPhos, (S)-MeO-BIPHEP, (R)-P-Phos, (R)-C3-TunePhos, (R)-C4-TunePhos, (R)-C2-TunePhos, or (S)-BINAP, preferably (S)-SegPhos.

[0024] Based on the above technical solution, preferably, the catalyst is prepared by dissolving the palladium precursor and the chiral bisphosphine ligand in an organic solvent under nitrogen protection, and stirring at room temperature to 30°C for 30-90 minutes, preferably at 30°C for 60 minutes.

[0025] Based on the above technical solution, preferably, the specific reaction steps of the method are as follows:

[0026] In a nitrogen-filled glove box, a palladium precursor and a chiral bisphosphine ligand were added to a reaction tube, followed by an organic solvent. The mixture was stirred in an oil bath at room temperature (-30°C) for 30-90 minutes. Then, in the same nitrogen-filled glove box, cis-2,3-diphenyl-1-toluenesulfonylpropionic acid derivative 1, molecular sieves, and the organic solvent were added and stirred until homogeneous. Borohydride was then added while stirring, and the reaction was carried out at 10-40°C for 8-72 hours to obtain chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative 2. After the reaction was complete, a saturated ammonium chloride aqueous solution was added to quench the reaction, and a small amount of ethyl acetate was added to dilute the reaction solution. The mixture was separated, extracted with ethyl acetate, and the organic phase was collected. The organic phase was then dried with anhydrous sodium sulfate, filtered, and the solvent was removed. Silica gel was added, and column chromatography was used to separate the pure chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative 2.

[0027] For example: In a nitrogen-filled glove box, palladium acetate (0.015 mmol) and a chiral ligand (0.018 mmol) were added to a reaction tube, followed by tetrahydrofuran (1.5 mL). After stirring in an oil bath at 30 °C for 60 minutes, cis-2,3-diphenyl-1-toluenesulfonylpropidine (0.3 mmol) was added to the reaction tube in a nitrogen-filled glove box. Molecular sieve (150 mg) and tetrahydrofuran (1.5 mL) were stirred until homogeneous. Then, pinacol borane was added while stirring. The reaction was carried out at 30 °C for 36 h. The reaction was quenched by adding saturated ammonium chloride aqueous solution. The reaction solution was diluted with 5 mL of ethyl acetate. The mixture was separated and extracted with ethyl acetate (3 × 10 mL). The organic phase was collected and dried with anhydrous sodium sulfate. The mixture was filtered, the solvent was removed, and silica gel was added. The mixture was separated by column chromatography to obtain pure chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide 2.

[0028] The present invention has the following advantages:

[0029] 1. The raw materials are simple and readily available, and the operation is simple.

[0030] 2. It has high reactivity, complete conversion of raw materials, convenient separation, and can obtain high-purity products. The enantiomeric excess can reach 93%, and the yield can reach 96%.

[0031] 3. The reaction conditions are mild; the reaction can be carried out at 30 degrees Celsius. Detailed Implementation

[0032] The present invention is described in detail below through embodiments; however, the present invention is not limited to the embodiments described below.

[0033] The following examples illustrate the synthesis of cis-2,3-diphenyl-1-toluenesulfonylpropionic acid, referenced in: (a) Bera, M.; Roy, S. Tetrahedron Lett. 2007, 48, 7144. (b) Pfeifer, L.; Gouverneur, V. Org. Lett. 2018, 20, 1576. (c) Han, X.; Hu, J.; Chen, C.; Yuan, Y.; Shi, Z. Chem. Commun. 2019, 55, 6922. (d) Luo, A.; Bao, Y.; Liu, X.; Liu, J.; Han, W.; Yang, G.; Yang, Y.; Bin, Z.; You, J. A. J. A. M. Chem. Soc. 2024, 146, 6240.

[0034] Example 1: Condition Optimization

[0035] In a nitrogen-filled glove box, palladium precursor (0.01 mmol) and chiral ligand L (0.015 mmol) were added to the reaction tube, followed by solvent (1 mL). After stirring in an oil bath at 30 °C for 60 minutes, cis-2,3-diphenyl-1-toluenesulfonylpropidine 1a (0.2 mmol), molecular sieve (100 mg), and solvent (1 mL) were added to the nitrogen-filled glove box and stirred until homogeneous. Then, borohydride (0.3 mmol) was added while stirring. After stirring at 30 °C for 36 h, the reaction was quenched with saturated ammonium chloride aqueous solution, and the reaction solution was diluted with 5 mL of ethyl acetate. The mixture was separated, extracted with ethyl acetate (3 × 10 mL), and the organic phase was collected. The organic phase was then dried with anhydrous sodium sulfate, filtered, and the solvent was removed. Silica gel was added, and column chromatography (chromatographic solvent: petroleum ether, ethyl acetate volume ratio 8:1) was performed to obtain pure chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide 2a. The reaction formula is as follows:

[0036]

[0037] The yields were NMR yields, and the enantiomeric excess of the products was determined by chiral liquid chromatography, as shown in Table 1.

[0038] Table 1. Optimization of synthetic conditions for chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide compounds [a]

[0039]

[0040]

[0041] [a] 1a(0.2mmol),[H](0.3mmol),[Pd](0.01mmol),L(0.015mmol),solvent(2mL),MS(100mg)at 30℃for 36h. [b] Determined by 1 H NMR. [c] Determined by chiral HPLC. [d] L (0.012 mmol) was used.

[0042] Example 2: Palladium-catalyzed asymmetric hydrogenolysis of cis-2,3-diphenyl-1-toluenesulfonylaziridine derivatives to synthesize chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivatives

[0043] In a nitrogen-filled glove box, palladium acetate (0.015 mmol) and chiral ligand (S)-SegPhos (0.018 mmol) were added to a reaction tube, followed by tetrahydrofuran (1.5 mL). After stirring in an oil bath at 30 °C for 60 minutes, cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1 (0.3 mmol) was added to the reaction tube in a nitrogen-filled glove box. Molecular sieve (150 mg) and tetrahydrofuran (1.5 mL) were stirred until homogeneous. Then, pinacol borane (0.45 mmol) was added while stirring. The reaction was carried out at 30 °C for 36 h. The reaction was quenched with saturated ammonium chloride aqueous solution, and 5 mL of ethyl acetate was added to dilute the reaction solution. The mixture was separated, extracted with ethyl acetate (3 × 10 mL), and the organic phase was collected. The organic phase was then dried with anhydrous sodium sulfate, filtered, and the solvent was removed. Silica gel was added, and column chromatography (chromatographic solvent: petroleum ether: ethyl acetate, volume ratio 8:1) was performed to obtain pure chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide 2. The reaction formula is as follows:

[0044]

[0045] The yield was the separation yield, and the enantiomeric excess of the product was determined by chiral liquid chromatography.

[0046] This invention relates to the asymmetric hydrogenolysis of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivatives catalyzed by palladium to synthesize chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivatives, achieving an enantiomeric excess of up to 93% and a yield of up to 96%. This invention offers advantages such as simple and practical operation, readily available raw materials, high enantioselectivity, good yield, and commercially available catalysts.

[0047] (R)-N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide(2a):

[0048] 98.1 mg, 93% yield, white solid, known compound, R f =0.21 (petroleum ether / ethyl acetate 8 / 1), 91% ee, [α] 20 D =31.48

[0049] 21.6. HPLC: Chiralpak OJ-H column, 220 nm, 30 °C, n-hexane / isopropanol = 75 / 25, flow = 0.8 mL / min, retention time 12.8 min (minor) and 20.8 min (major).

[0050] (R)-N-(1,2-di-p-tolylethyl)-4-methylbenzenesulfonamide(2b):

[0051] 107.7 mg, 95% yield, white solid, melting range 103-104 °C, new compound, R f =0.23 (petroleum ether / ethyl acetate 8 / 1), 87% ee,

[0052] 127.2, 126.8, 59.1, 43.7, 21.6, 21.2. The HPLC: Chiralpak OJ-H column, 220 nm, 30 °C, n-hexane / isopropanol = 90 / 10, flow = 1.0 mL / min, retention time 14.4 min (minor) and 21.0 min (major).

[0053] (R)-N-(1,2-di-m-tolylethyl)-4-methylbenzenesulfonamide(2c):

[0054] 106.6 mg, 92% yield, pale yellow gelatinous liquid, new compound, R f =0.22 (petroleum ether / ethyl acetate 8 / 1), 86% ee, [α] 20 D =

[0055] 137.2, 136.4, 130.1, 129.3, 128.6, 128.3, 128.3, 127.7, 127.5, 127.2, 126.4, 124.0, 59.3, 44.2, 21.6, 21.4, 21.4. HPLC: Chiralpak OJ-H column, 220 nm, 30 °C, n-hexane / isopropanol = 85 / 15, flow = 1.0 mL / min, retention time 8.8 min (minor) and 11.4 min (major).

[0056] (R)-N-(1,2-di-o-tolylethyl)-4-methylbenzenesulfonamide(2d):

[0057] 49.5 mg, 43% yield, white solid, melting range 150-151 °C, new compound, R f =0.24 (petroleum ether / ethyl acetate 8 / 1), 93% ee,

[0058] 19.3, 19.0. The HPLC: Chiralpak OD-3 column, 220 nm, 30 °C, n-hexane / isopropanol = 92 / 8, flow = 0.8 mL / min, retention time 13.1 min (minor) and 14.1 min (major).

[0059] (R)-N-(1,2-bis(4-ethylphenyl)ethyl)-4-methylbenzenesulfonamide(2e):

[0060] 118.0 mg, 96% yield, white solid, melting range 116-117 °C, new compound, R f =0.25 (petroleum ether / ethyl acetate 8 / 1), 88% ee,

[0061] 129.3, 129.3, 128.2, 127.9, 127.3, 126.9, 59.0, 43.8, 28.6, 28.6, 21.6, 15.7, 15.7. The HPLC: Chiralpak OJ-H column, 220 nm, 30 °C, n-hexane / isopropanol = 95 / 5, flow = 1.0 mL / min, retention time 20.1 min (minor) and 23.6 min (major).

[0062] (R)-N-(1,2-bis(4-fluorophenyl)ethyl)-4-methylbenzenesulfonamide (2f): 107.9 mg, 93% yield, white solid, melting range 171-172 °C, new compound, R f =0.22 (petroleum ether / ethyl acetate 8 / 1), 86% ee,

[0063] 3.2Hz), 130.9(d, 3 J C-F =8.0Hz), 129.5, 128.5(d, 3 J C-F =8.2Hz), 127.1, 115.5(d, 2 J C-F =21.3Hz), 115.4(d, 2 J C-F =21.6Hz), 58.9, 43.3, 21.6. 19 F NMR (376MHz, CDCl3) δ -114.76, -115.75. HPLC: Chiralpak OJ-H, 220nm, 30℃, n-hexane / isopropanol = 85 / 15, flow = 1.0mL / min, retention time 14.2min (minor) and 17.6min (major).

[0064] (R)-N-(1,2-bis(3-fluorophenyl)ethyl)-4-methylbenzenesulfonamide(2g):

[0065] 95.9 mg, 83% yield, white solid, melting range 124-125 °C, new compound, R f =0.22 (petroleum ether / ethyl acetate 8 / 1), 87% ee,

[0066] 1 J C-F =246.7Hz), 162.7(d, 1 J C-F =246.7Hz), 143.4, 142.9 (d, 3 J C-F =6.9Hz), 138.5(d, 3 J C-F =7.3Hz), 136.7, 130.1(d, 3 J C-F=8.3Hz), 130.0(d, 3 J C-F =8.3Hz),129.4,127.0,125.0(d, 4 J C-F =2.8Hz), 122.3(d, 4 J C-F =2.9Hz), 116.0(d, 2 J C-F =21.2Hz), 114.5(d, 2 J C-F =21.2Hz), 114.0(d, 2 J C-F =21.0Hz), 113.7(d, 2 J C-F =22.1Hz), 58.6(d, 4 J C-F =1.9Hz), 43.6(d, 4 J C-F =1.6Hz), 21.4. 19 F NMR (376MHz) δ -112.68, -112.71. HPLC: Chiralpak OD-H column, 220nm, 30℃, n-hexane / isopropanol = 90 / 10, flow = 1.0mL / min, retention time 12.2min (minor) and 14.3min (major).

[0067] (R)-N-(1,2-di(benzofuran-5-yl)ethyl)-4-methylbenzenesulfonamide(2h):

[0068] 121.5 mg, 94% yield, pale yellow solid, melting range 157-158 °C, new compound, R f =0.42 (petroleum ether / ethyl acetate 5 / 1), 80%

[0069] 5.9Hz,1H),4.61(dt,J=8.2,6.1Hz,1H),3.20-2.99(m,2H),2.27(s,3H). 13C10 NMR (100MHz, CDCl3) δ 154.4, 154.1, 145.5, 145.4, 143.0, 137.0, 135.4, 131.0, 129.1, 127.8, 127.5, 127.1, 125.6, 123.2, 121.8, 119.7, 111.5, 111.3, 106.7, 106.6, 59.9, 44.5, 21.5. HPLC: Chiralpak OJ-H column, 220nm, 30℃, n-hexane / isopropanol = 65 / 35, flow = 0.8mL / min, retention time 24.6min (minor) and 29.6min (major).

[0070] The core skeleton of the aforementioned chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative is chiral β-phenylethylamine. Currently, most clinically used adrenergic receptor agonist drugs have the basic structure of chiral β-phenylethylamine, such as methyldopa, ephedrine, and pseudoephedrine.

Claims

1. A method for the synthesis of chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide by palladium catalyzed asymmetric hydrogenolysis, characterized in that, Using palladium and chiral bisphosphine ligands as catalytic systems, borohydride as hydrogen source, and cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative as substrate 1, chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative 2 was synthesized by asymmetric hydrogenolysis. The reaction formula is as follows: In the formula: Ar is a benzene ring, an aromatic heterocycle, or a benzene ring containing a substituent, wherein the substituent is one of C1-C20 alkyl, aryl, fluorine, or chlorine; The catalyst is a complex of a palladium precursor and a chiral bisphosphine ligand.

2. The method as described in claim 1, characterized in that: The borohydride is one of lithium borohydride, sodium borohydride, potassium borohydride, pinacol borane, or catechol borane.

3. The method as described in claim 1, characterized in that: The reaction temperature is 10–40℃; the reaction time is 8–72 hours.

4. The method according to claim 1, characterized in that, The reaction solvent is an organic solvent, which is one or more of tetrahydrofuran, 2-methyltetrahydrofuran, 1,2-dichloroethane, ethylene glycol dimethyl ether, ethyl acetate, N,N-dimethylformamide, toluene, 1,4-dioxane, and isopropanol; the reaction temperature is 10–40°C; and the reaction time is 24–72 hours.

5. The method as described in claim 1, characterized in that: The molar ratio of the palladium precursor to cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1 is 0.05:1 to 0.1:1, and the molar ratio of the chiral bisphosphine ligand to cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1 is 0.06:1 to 0.15:

1.

6. The method as described in claim 1, characterized in that: The molar ratio of the borohydride and cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1 is 1.2:1 to 2.0:

1.

7. The method as claimed in claim 1, characterized in that: The amount of solvent used is 0.5 to 5 mL of solvent per 0.2 mmol of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1.

8. The method according to claim 1, characterized in that: The palladium precursor is palladium acetate, bis(acetylacetone)palladium, bis(di-benzylacetone)palladium, bisacetonitrile palladium chloride, bis(tri-tert-butylphosphine)palladium, or bis(cyanobenzene)palladium dichloride; the chiral ligand is (S)-SegPhos, (R)-PhanePhos, (S,S)-ChiraPhos, (S)-DM-SegPhos, (S)-DTBM-SegPhos, (S)-SynPhos, (S)-MeO-BIPHEP, (R)-P-Phos, (R)-C3-TunePhos, (R)-C4-TunePhos, (R)-C2-TunePhos, or (S)-BINAP; the catalyst is prepared by dissolving the palladium precursor and the chiral bisphosphine ligand in an organic solvent under nitrogen protection and stirring at room temperature to 30°C for 30-90 minutes.

9. The method according to claim 1, characterized in that: The method further includes a molecular sieve, wherein the molecular sieve is... or Molecular sieves are used at a dosage of 50-150 mg per 0.2-0.3 mmol of cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative.

10. The method according to claim 1, characterized in that, The specific reaction steps of the method are as follows: In a nitrogen-filled glove box, a palladium precursor and a chiral bisphosphine ligand are added to a reaction tube, followed by an organic solvent. The mixture is stirred in an oil bath at room temperature to 30°C for 30-90 minutes. Then, in a nitrogen-filled glove box, cis-2,3-diphenyl-1-toluenesulfonylpropidine derivative 1, a molecular sieve, and an organic solvent are added and stirred until homogeneous. Subsequently, borohydride is added while stirring, and the reaction is carried out at 10-40°C for 8-72 hours to obtain a chiral N-(1,2-diphenylethyl)-4-methylbenzenesulfonamide derivative 2.

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