A method for highly stereoselective synthesis of 3-vinylindol-2-one derivatives

Abstract

The present invention belongs to the field of asymmetric catalytic synthesis, and specifically discloses a method for highly stereoselective synthesis of 3-vinylindole-2-one derivatives. The present invention uses an iridium-catalyzed diastereo- and enantioselective synthesis method of 3-vinylindole-2-one derivatives from 1-(2-aminophenyl)prop-2-en-1-ol derivatives and sulfonium ylides, and obtains 3-vinylindole-2-one derivatives with good stereoselectivity. The advantages of the method of the present invention are: simple reaction operation, simple and easily available raw materials, mild reaction conditions, wide substrate scope, high efficiency, and good diastereo- and enantioselectivity.

Description

Technical Field

[0001] The present invention belongs to the field of asymmetric catalytic organic synthesis, and particularly relates to a diastereo- and enantioselective synthesis reaction of 3-vinylindol-2-one derivatives from 1-(2-aminophenyl)prop-2-en-1-ol derivatives and sulfoxonium ylides. Background Art

[0002] Iridium-catalyzed asymmetric allylic substitution (AAS) has been established as a powerful tool for the direct construction of chiral carbon-carbon and carbon-heteroatom bonds (Hartwig, J. Acc. Chem. Res. 2010, 43, 1461 - 1475). By using unactivated allylic alcohols as substrates and adding an additional Lewis acid as a promoter, this iridium-catalyzed AAS has been extended to more readily available substrates for the construction of bioactive heterocyclic compounds.

[0003] Palladium-catalyzed decarboxylation of vinylbenzoxazinones to form π-allyl Pd II -species can also synthesize various cycloaddition products (Xiao, W. J, Chem. Soc. Rev., 2017, 46, 4135 - 4149). In 2014, the Lu and Xiao groups reported a method for the diastereo- and enantioselective synthesis of benzheterocycles from vinylbenzoxazinones and sulfur ylides (Xiao, W.-J. Nat. Commun. 2014, 5, 5500.), providing a method for chiral 3-vinylindoline derivatives with excellent diastereo- and enantioselectivity. Subsequently, the Wang group reported a method for the synthesis of 2,3-disubstituted indoline derivatives from vinylbenzoxazinones and sodium N-formylhydrazone, which requires the synthesis of oxazinone derivatives with relatively more synthesis steps (Ashfeld, B. L, Org. Lett. 2020, 22, 6605 - 6609).

[0004] It has been reported that sulfoxonium ylides have similar reactivity to sulfonium ylides but weaker nucleophilicity. In addition, sulfoxonium ylides are also widely used as carbene precursors for the generation of carbene species, especially in the presence of iridium catalysts. Summary of the Invention

[0005] The present invention discloses a diastereo- and enantioselective synthesis reaction of 3-vinylindol-2-one derivatives using iridium as a catalyst, a chiral ligand, sulfoxonium ylide as a carbene precursor, and 1-(2-aminophenyl)prop-2-en-1-ol derivatives.

[0006] The specific reaction formula of the present invention is as follows:

[0007]

[0008] Wherein:

[0009] R 1 is Ts, Ns, Ms, 4-MeOC6H4SO2;

[0010] R 2 is H, 3-F, 4-Br, 4-MeO, 5-Me, 5-MeO, 5-Cl, 6-Cl, 6-Me;

[0011] Ar is Ph, 2-MeC6H4, 3,5-Me2C6H3, 3-ClC6H4, 4-MeC6H4, 4-CF3C6H4, n-Pr, EtO.

[0012] A method for the chemo- and enantioselective insertion of sulfoxonium ylides into 1-(2-aminophenyl)prop-2-en-1-ols, specifically: add an iridium catalyst, a chiral ligand, and a certain amount of solvent to a dry reaction tube, stir at room temperature for 10 minutes, then add 1-(2-aminophenyl)prop-2-en-1-ol derivative (2) and sulfoxonium ylide (1), add an additive, an acid, and a certain amount of solvent under argon protection, and stir and react at a certain temperature to obtain the chiral 3-vinylindol-2-one derivative (3).

[0013] The chiral ligand used is as follows:

[0014]

[0015] Among them, the optimal chiral ligand is L1.

[0016] The specific structural formula of the sulfoxonium ylide is as follows:

[0017]

[0018] The structural formula of the 1-(2-aminophenyl)prop-2-en-1-ol derivative is as follows:

[0019]

[0020] The solvents for the reaction are: toluene, tetrahydrofuran, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, hexafluoroisopropanol, methylcyclohexane, cyclohexane, cyclopentane, n-hexane, methyl tert-butyl ether, and diethyl ether, etc. Among them, the optimal solvent is dichloroethane.

[0021] The reaction catalyst is: [Ir(cod)Cl]2.

[0022] The molar ratio of iridium catalyst, chiral ligand, 1-(2-aminophenyl)prop-2-en-1-ol derivative and sulfoxonium ylide in the reaction is: 0.003 - 0.006:0.012 - 0.024:1:1 - 2.5, and the optimal molar ratio is: 0.003:0.012:1:2.5.

[0023] When the 1-(2-aminophenyl)prop-2-en-1-ol derivative is 1 equivalent, the concentration of the reaction solution is: 0.01 - 0.10 mol / L, and the optimal concentration is 0.05 mol / L.

[0024] The reaction temperature is: 40 - 60 °C, and the optimal reaction temperature is 45 °C.

[0025] The acids for the reaction are: trifluoroacetic acid, trichloroacetic acid, p-toluenesulfonic acid, methanesulfonic acid, bis(trifluoromethanesulfonyl)imide, boron trifluoride etherate, ferrous trifluoromethanesulfonate, zinc trifluoromethanesulfonate, scandium trifluoromethanesulfonate, and the best acid is trifluoroacetic acid; when the 1-(2-aminophenyl)prop-2-en-1-ol derivative is 1 equivalent, the equivalent of the reaction acid is 1 - 4:1, and the optimal equivalent of the reaction acid is: 3:1 equivalent.

[0026] Additives can also be added during the reaction, and the additives used are: molecular sieves, molecular sieves, molecular sieves, among which molecular sieves are the best, and its addition amount is 250 mg / mmol when the 1-(2-aminophenyl)prop-2-en-1-ol derivative is 1 equivalent.

[0027] Beneficial effects and advantages

[0028] The present invention designs a method for the chemoselective and enantioselective insertion of sulfoxonium carbene into 1-(2-aminophenyl)prop-2-en-1-ol derivatives, and diastereoselectively and enantioselectively synthesizes 3-vinylindol-2-one derivatives to obtain chiral indoline products. It provides a simple route for the synthesis of highly substituted indoline compounds with two stereocenters having good stereoselectivity. In addition, the present invention also represents an important example of the transformation of sulfoxonium ylides.

[0029] The advantages of the method of the present invention are: simple reaction operation, mild conditions, simple and easily available raw materials, wide substrate scope, high efficiency, good diastereoselectivity and enantioselectivity. Description of the drawings

[0030] Figure 1 For the 3aa obtained in Example 1 1 1H-NMR (proton nuclear magnetic resonance);

[0031] Figure 2 For the 3aa obtained in Example 113 C-NMR (Carbon Nuclear Magnetic Resonance);

[0032] Figure 3 It is the HRMS (High Resolution Mass Spectrometry) of 3aa obtained in Example 1. Detailed Implementation Modes

[0033] The present invention will be further described below through specific examples, and the present invention is not limited to the following examples.

[0034] Example 1

[0035]

[0036] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, then add sulfonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3 (49.1 mg, 75% yield), melting point: 131 - 133 °C; enantioselectivity: 99% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 6.38 min (minor) and 7.58 min (major). [α] D 20 : -104.2 (c = 0.25, CH2Cl2; 99% ee). 11H NMR (400 MHz, CDCl3) δ 7.99 (dd, J = 8.4, 1.2 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.33 - 7.26 (m, 2H), 7.06 (d, J = 7.5 Hz, 1H), 7.01 (td, J = 7.2, 1.4 Hz, 1H), 6.04 (ddd, J = 16.9, 10.0, 8.5 Hz, 1H), 5.74 (d, J = 4.1 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H), 5.15 (d, J = 16.9 Hz, 1H), 3.87 (dd, J = 8.5, 4.1 Hz, 1H), 3.27 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 194.9, 141.3, 137.0, 134.2, 133.7, 130.2, 129.1, 129.1, 129.0, 125.9, 123.2, 117.5, 112.4, 71.2, 50.2, 39.8. HRMS (ESI) calcd. for C 19 H 17 NNaO3 [M + Na] + : 328.1002; Found: 328.0999.

[0037] Example 2

[0038] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and stir in an oil bath at 40 °C for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (31.4 mg, 48% yield, 99% ee).

[0039] Example 3

[0040] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L2 (10.7 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, and then sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) are added. After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 40 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (3.3 mg, <5% yield, 72% ee).

[0041] Example 4

[0042] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L3 (9.3 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, and then sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) are added. After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 40 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (6.5 mg, <10% yield, 87% ee).

[0043] Example 5

[0044] Add [Ir(cod)Cl]2 (1.3 mg, 0.002 mmol) to a dry reaction tube. The chiral ligand L1 (12.9 mg, 0.008 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, and then sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) are added. After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 40 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (16.4 mg, 25% yield, 67% ee).

[0045] Example 6

[0046] To a dry reaction tube was added [Ir(cod)Cl]2 (2.7 mg, 0.004 mmol), and the chiral ligand L1 (8.1 mg, 0.016 mmol) was dissolved in 0.5 mL of dichloroethane. It was stirred at room temperature for 10 minutes, then sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 40 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (19.6 mg, 30% yield, 85% ee).

[0047] Example 7

[0048] To a dry reaction tube was added [Ir(cod)Cl]2 (5.4 mg, 0.008 mmol), and the chiral ligand L1 (16.2 mg, 0.032 mmol) was dissolved in 0.5 mL of dichloroethane. It was stirred at room temperature for 10 minutes, then sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 40 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (27.5 mg, 42% yield, 95% ee).

[0049] Example 8

[0050] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg) and 1.5 mL of iron(II) trifluoromethanesulfonate in dichloroethane (212.4 mg, 0.6 mmol). Place it in an oil bath at 40 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (20.9 mg, 32% yield, 67% ee).

[0051] Example 9

[0052] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol). Place it in an oil bath at 50 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (43.2 mg, 66% yield, 92% ee).

[0053] Example 10

[0054] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 60 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (33.4 mg, 51% yield, 88% ee).

[0055] Example 11

[0056] To a dry reaction tube was added [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol), and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (22.8 mg, 0.2 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (22.2 mg, 34% yield, 44% ee).

[0057] Example 12

[0058] To a dry reaction tube was added [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol), and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (45.6 mg, 0.4 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (36.0 mg, 55% yield, 55% ee).

[0059] Example 13

[0060] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (91.2 mg, 0.8 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (26.2 mg, 40% yield, 96% ee).

[0061] Example 14

[0062] Add [Ir(cod)Cl2] (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1a (98.5 mg, 0.5 mmol) and hydroxyallylaniline 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg) and 1.5 mL of dichloroethane trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (26.2 mg, 40% yield, 82% ee).

[0063] Example 15

[0064] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (98.5 mg, 0.5 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg) and 1.5 mL of dichloroethane trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (22.9 mg, 35% yield, 88% ee).

[0065] Example 16

[0066] To a dry reaction tube was added [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol), and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, sulfoxonium ylide 1 (39.2 mg, 0.2 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (19.6 mg, 30% yield, 89% ee).

[0067] Example 17

[0068] To a dry reaction tube was added [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol), and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, sulfoxonium ylide 1 (58.8 mg, 0.3 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (40.5 mg, 62% yield, 98% ee).

[0069] Example 18

[0070] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add sulfoxonium ylide 1 (78.4 mg, 0.4 mmol) and N-(2-(1-hydroxyallyl)phenyl)methanesulfonamide 2 (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product (34.7 mg, 53% yield, 96% ee).

[0071] Example 19:

[0072]

[0073] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1a (98.5 mg, 0.5 mmol) and 2b (60 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a yellow solid product 3ab (46.7 mg, 58% yield), melting point: 73 - 75 °C; enantioselectivity: 99% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak AD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 10.83 min (minor) and 18.18 min (major). [α] D 20 : -47.8 (c = 0.25, CH2Cl2; 99% ee). 11H NMR (400 MHz, CDCl3) δ 8.0 (d, J = 7.2 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H), 7.62 (dd, J = 10.5, 7.9 Hz, 2H), 7.49 (t, J = 7.7 Hz, 2H), 7.26 (d, J = 13.4 Hz, 3H), 7.04 - 6.95 (m, 2H), 5.39 (ddd, J = 16.9, 9.9, 8.6 Hz, 1H), 5.32 (d, J = 5.0 Hz, 1H), 5.00 (d, J = 9.9 Hz, 1H), 4.95 (d, J = 16.9 Hz, 1H), 3.80 (dd, J = 8.6, 5.0 Hz, 1H), 2.39 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.4, 144.5, 141.6, 136.9, 134.9, 134.3, 133.8, 131.3, 129.9, 129.2, 129.0, 128.9, 127.6, 125.6, 124.3, 117.6, 115.2, 71.2, 50.4, 21.7. HRMS (ESI): calculated for C 24 H 21 NO3S [M + H]+: 404.1315; Found: 404.1318.

[0074] Example 20:

[0075]

[0076] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, then 1a (98.5 mg, 0.5 mmol) and 2c (66.8 mg, 0.2 mmol) were added. After evacuating and refilling the reaction tube with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the yellow oil product 3ac (45.2 mg, 52% yield); enantioselectivity: 91% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 80 / 20, flow rate 2.0 mL / min, λ = 215 nm, t R = 8.06 min (minor) and 10.14 min (major). [α] D 20 : -10.2 (c = 0.25, CH2Cl2; 91% ee). 1 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 9.0 Hz, 2H), 8.11 (d, J = 9.0 Hz, 2H), 7.98 (dd, J = 8.4, 1.2 Hz, 2H), 7.67 - 7.63 (m, 1H), 7.57 - 7.50 (m, 3H), 7.32 - 7.27 (m, 1H), 7.08 - 7.00 (m, 2H), 5.59 (ddd, J = 16.9, 10.0, 8.3 Hz, 1H), 5.51 (d, J = 4.4 Hz, 1H), 5.07 (d, J = 10.0 Hz, 1H), 4.97 (d, J = 16.9 Hz, 1H), 3.84 (dd, J = 8.3, 4.4 Hz, 1H). 13 13C NMR (101 MHz, CDCl3) δ 193.7, 150.4, 144.0, 140.6, 136.5, 134.1, 133.7, 131.0, 129.2, 129.0, 129.0, 128.7, 126.0, 124.7, 124.4, 117.9, 114.4, 71.2, 50.1. HRMS (ESI): calculated for C 23 H 18 N2O5S [M + H] + : 435.1009; Found: 435.1010.

[0077] Example 21:

[0078]

[0079] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1a (98.5 mg, 0.5 mmol) and 2d (63.8 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a yellow oil product 3ac (45.5 mg, 54% yield); enantioselectivity: 88% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 7.99 min (minor) and 9.47 min (major). [α] D 20 : +3.1 (c = 0.25, CH2Cl2; 88% ee). 1 1H NMR (400 MHz, CDCl3) δ 8.01 - 7.99 (m, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.62 - 7.58 (m, 2H), 7.48 (t, J = 7.7 Hz, 2H), 7.28 - 7.24 (m, 1H), 7.03 - 6.96 (m, 2H), 6.93 (d, J = 9.0 Hz, 2H), 5.44 (ddd, J = 16.9, 9.9, 8.7 Hz, 1H), 5.31 (d, J = 5.1 Hz, 1H), 5.03 (d, J = 9.9 Hz, 1H), 4.96 (d, J = 16.9 Hz, 1H), 3.83 (s, 3H), 3.82 - 3.79 (m, 1H). 13 13C NMR (101 MHz, CDCl3) δ 194.5, 163.6, 141.5, 136.7, 134.2, 133.7, 131.2, 129.7, 129.3, 129.1, 128.9, 128.8, 125.5, 124.2, 117.6, 115.1, 114.3, 71.2, 55.7, 50.4. HRMS (ESI): calculated for C 24 H 21 NO4S [M + H]+ : 420.1264; Found: 420.1265.

[0080] Example 22:

[0081]

[0082] Add 639.2 mg (3.0 mmol) of N-(2-formyl-3-methylphenyl)methanesulfonamide to a 50 mL reaction tube, dissolve it in tetrahydrofuran, and under a vacuum and argon atmosphere, add vinylmagnesium chloride dropwise at 0 °C and stir for half an hour. Then, let it react at room temperature for 8 h, quench with saturated ammonium chloride solution, and extract the reaction solution with a small amount of water and ethyl acetate multiple times. Subsequently, evaporate the solvent under reduced pressure. The product is purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 20 - 1 / 3] to obtain 542 mg of a white solid, with a yield of 75%, melting point: 78 - 80 °C. 1 HNMR(400 MHz, CDCl3) δ 8.80 (s, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.15 (t, J = 7.9 Hz, 1H), 6.92 (d, J = 7.6 Hz, 1H), 6.05 (ddd, J = 17.1, 10.5, 4.3 Hz, 1H), 5.71 (s, 1H), 5.30 (d, J = 17.1 Hz, 1H), 5.23 (d, J = 10.5 Hz, 1H), 3.53 (brs, 1H), 2.88 (s, 3H), 2.31 (s, 3H). 13 C NMR(100 MHz, CDCl3) δ 160.1, 138.6, 137.3, 129.8, 123.2, 115.5, 109.7, 106.6, 74.1, 55.5, 39.6. HRMS(ESI): calculated for C 11 H 15 NO3S [M + H] + : 242.0845; Found: 242.0845.

[0083] Example 23:

[0084]

[0085] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. Dissolve the chiral ligand L1 (12.2 mg, 0.024 mmol) in 0.5 mL of dichloroethane, stir at room temperature for 10 minutes, then add 1a (98.5 mg, 0.5 mmol) and 2e (48 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ae (54.6 mg, 80% yield), melting point: 141 - 143 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 5.14 min (minor) and 6.86 min (major). [α] D 20 : -9.0 (c = 0.25, CH2Cl2; 98% ee). 1 1H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.1 Hz, 2H), 7.66 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 7.23 - 7.11 (m, 2H), 6.80 (d, J = 7.0 Hz, 1H), 5.99 (ddd, J = 16.9, 10.0, 8.6 Hz, 1H), 5.74 (d, J = 2.6 Hz, 1H), 5.27 (d, J = 10.0 Hz, 1H), 5.13 (d, J = 16.9 Hz, 1H), 3.81 (dd, J = 8.6, 2.6 Hz, 1H), 3.28 (s, 3H), 2.10 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.6, 141.3, 136.1, 135.6, 134.2, 133.4, 129.2, 129.0, 127.8, 124.8, 117.5, 109.8, 71.4, 49.0, 39.9, 18.0. HRMS (ESI): calculated for C 19 H 19 NO3S [M + H] + : 342.1158; Found: 342.1156.

[0086] Example 24:

[0087]

[0088] 698.4 mg (3.0 mmol) of N-(2-formyl-3-chlorophenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, followed by stirring for half an hour. Then, the reaction was allowed to proceed at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted multiple times with a small amount of water and ethyl acetate. Subsequently, the solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 10 - 1 / 5] to obtain 525 mg of a white solid in a yield of 67%, melting point: 56 - 58 °C. 1 H NMR (400 MHz, CDCl3) δ 8.87 (s, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.21 (t, J = 8.1 Hz, 1H), 7.14 (d, J = 8.1 Hz, 1H), 6.11 - 6.00 (m, 2H), 5.4 (d, J = 16.5 Hz, 1H), 5.29 (d, J = 10.2 Hz, 1H), 3.30 (brs, 1H), 2.94 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 138.4, 136.5, 133.5, 129.7, 127.0, 125.4, 118.6, 115.7, 71.8, 39.9. HRMS (ESI): calculated for C 11 H 15 NO3S [M + H] + : 262.0299; Found: 262.0297.

[0089] Example 25:

[0090]

[0091] [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) was added to a dry reaction tube, and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2f (52.5 mg, 0.2 mmol) were added, and after evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3fa (53.4 mg, 74% yield), melting point: 123 - 125 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 5.07 min (minor) and 6.90 min (major). [α] D 20 : -53.4 (c = 0.25, CH2Cl2; 98% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 7.3 Hz, 1H), 7.67 (t, J = 7.3 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.26 - 7.20 (m, 2H), 6.96 (dd, J = 6.9, 2.0 Hz, 1H), 6.02 (ddd, J = 16.9, 10.0, 8.1 Hz, 1H), 5.8 (d, J = 2.5 Hz, 1H), 5.33 (d, J = 10.0 Hz, 1H), 5.25 (d, J = 16.9 Hz, 1H), 3.93 (dd, J = 8.6, 2.5 Hz, 1H), 3.29 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.2, 142.8, 134.5, 134.1, 133.1, 132.0, 130.6, 129.2, 129.1, 127.9, 123.9, 118.4, 110.7, 71.3, 48.9, 40.3. HRMS (ESI): calculated for C 18 H 16 ClNO3S [M + H] + : 362.0612; Found: 362.0610.

[0092] Example 26:

[0093]

[0094] 698 mg (3.0 mmol) of N-(2-formyl-4-chlorophenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, followed by stirring for half an hour. Then, the reaction was allowed to proceed at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted multiple times with a small amount of water and ethyl acetate. Subsequently, the solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 30 - 1 / 3] to obtain 375 mg of a white solid, with a yield of 49% and a melting point of 52 - 54 °C. 1 H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.28 (dd, J = 8.8, 2.5 Hz, 1H), 7.19 (d, J = 2.5 Hz, 1H), 6.08 (ddd, J = 17.2, 10.4, 5.0 Hz, 1H), 5.44 (d, J = 17.2, 1.2 Hz, 1H), 5.37 - 5.33 (m, 2H), 2.99 (s, 3H), 2.84 (s, 1H). 13 C NMR (100 MHz, CDCl3) δ 137.7, 137.4, 130.2, 129.6, 127.6, 123.3, 122.8, 116.3, 74.4, 40.0. HRMS (ESI): calculated for C 10 H 12 ClNO3S [M + H] + : 262.0299; Found: 262.0299.

[0095] Example 27:

[0096]

[0097] [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) was added to a dry reaction tube, and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2g (52.5 mg, 0.2 mmol) were added, and after evacuating and refilling the reaction tube with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ag (54.2 mg, 75% yield), melting point: 145 - 147 °C; enantioselectivity: 94% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 5.91 min (minor) and 7.67 min (major). [α] D 20 : -47.8 (c = 0.25, CH2Cl2; 94% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 7.4 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 7.16 (d, J = 1.2 Hz, 2H), 6.95 (d, J = 1.2 Hz, 1H), 5.94 (ddd, J = 17.0, 9.9, 8.5 Hz, 1H), 5.68 (d, J = 4.1 Hz, 1H), 5.17 (d, J = 9.9 Hz, 1H), 5.08 (d, J = 17.0 Hz, 1H), 3.75 (dd, J = 8.5, 4.1 Hz, 1H), 3.17 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.6, 140.1, 136.2, 134.3, 133.5, 132.1, 129.1, 129.02, 128.95, 128.3, 126.1, 118.1, 113.3, 71.4, 49.9, 40.0. HRMS (ESI): calculated for C 18 H 16 ClNO3S [M + H] + : 362.0612; Found: 362.0610.

[0098] Example 28:

[0099]

[0100] 687 mg (3.0 mmol) of N-(2-formyl-4-methoxyphenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, followed by stirring for half an hour. Then, the reaction was allowed to proceed at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted multiple times with a small amount of water and ethyl acetate. Subsequently, the solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 50 - 1 / 10] to obtain 385 mg of a yellow oil, with a yield of 50%. 1 H NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.42 (dd, J = 8.2, 0.9 Hz, 1H), 6.84 - 6.81 (m, 2H), 6.07 (ddd, J = 17.1, 10.5, 4.9 Hz, 1H), 5.43 (dt, J = 17.1, 1.4 Hz, 1H), 5.39 (d, J = 3.3 Hz, 1H), 5.30 (dt, J = 10.5, 1.4 Hz, 1H), 3.79 (s, 3H), 3.15 (brs, 1H), 2.95 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 157.5, 138.2, 135.4, 128.1, 124.9, 116.0, 114.4, 113.9, 73.4, 55.6, 39.5. HRMS (ESI): calculated for C 11 H 15 NO4S [M + H] + : 258.0795; Found: 258.0795.

[0101] Example 29:

[0102]

[0103] [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) was added to a dry reaction tube, and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2h (51.6 mg, 0.2 mmol) were added. After evacuating and filling the reaction tube with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ah (57.1 mg, 80% yield), melting point: 114 - 116 °C; enantioselectivity: 99% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak IA column, n-hexane / i-PrOH = 80 / 20, flow rate 2.0 mL / min, λ = 215 nm, t R = 7.30 min (minor) and 8.51 min (major). [α] D 20 : -42.2 (c = 0.25, CH2Cl2; 99% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J = 8.3 Hz, 2H), 7.32 - 7.29 (m, 3H), 7.27 - 7.25 (m, 1H), 7.06 (d, J = 6.9 Hz, 1H), 7.00 (td, J = 7.2, 1.3 Hz, 1H), 6.04 (ddd, J = 16.9, 10.0, 8.6 Hz, 1H), 5.72 (d, J = 4.0 Hz, 1H), 5.21 (d, J = 10.0 Hz, 1H), 5.14 (d, J = 16.9 Hz, 1H), 3.85 (dd, J = 8.6, 4.0 Hz, 1H), 3.27 (s, 3H), 2.44 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 195.0, 156.4, 136.8, 135.0, 134.2, 133.8, 131.8, 129.2, 129.0, 117.8, 114.1, 113.4, 112.0, 71.6, 55.9, 50.4, 39.3. HRMS (ESI): calculated for C 19 H 19 NO4S [M + H] + : 358.1108; Found: 358.1104.

[0104] Example 30:

[0105]

[0106] 639 mg (3.0 mmol) of N-(2-formyl-4-methylphenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, followed by stirring for half an hour. Then, the reaction was allowed to proceed at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted several times with a small amount of water and ethyl acetate. Subsequently, the solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 20 - 1 / 10] to obtain 434 mg of a yellow solid, with a yield of 60% and a melting point of 54 - 56 °C. 1 H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.16 (d, J = 2.5 Hz, 1H), 7.08 (d, J = 8.5 Hz, 1H), 6.63 (dd, J = 8.5, 2.5 Hz, 1H), 6.08 (ddd, J = 17.2, 10.5, 4.7 Hz, 1H), 5.37 (d, J = 17.2 Hz, 1H), 5.29 - 5.26 (m, 2H), 3.79 (s, 3H), 3.10 (brs, 1H), 2.97 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 160.1, 138.6, 137.3, 129.8, 123.2, 115.5, 109.7, 106.6, 74.1, 55.5, 39.6. HRMS (ESI): calculated for C 11 H 15 NO3S [M + H] + : 242.0845; Found: 242.0843.

[0107] Example 31:

[0108]

[0109] [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) was added to a dry reaction tube, and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2i (48.0 mg, 0.2 mmol) were added, and after evacuating and filling the reaction tube with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane, and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3ai (48.4 mg, 71% yield), melting point: 111 - 113 °C; enantioselectivity: 99% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 7.02 min (minor) and 7.92 min (major). [α] D 20 : -85.2 (c = 0.25, CH2Cl2; 99% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.4 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H), 6.95 - 6.90 (m, 2H), 6.54 (dd, J = 8.3, 2.2 Hz, 1H), 6.12 - 5.93 (m, 1H), 5.72 (d, J = 3.9 Hz, 1H), 5.19 (d, J = 9.9 Hz, 1H), 5.11 (d, J = 16.9 Hz, 1H) 3.82 (s, 3H), 3.26 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.8, 160.8, 142.5, 137.3, 134.1, 133.7, 129.1, 128.9, 126.3, 122.1, 117.1, 108.5, 99.3, 72.0, 55.7, 49.5, 39.7. HRMS (ESI): calculated for C 19 H 19 NO3S [M+Na] + : 364.0978; Found: 364.0975.

[0110] Example 32:

[0111]

[0112] 831 mg (3.0 mmol) of N-(2-formyl-5-bromophenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, and the mixture was stirred for half an hour. Then, it was allowed to react at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted with a small amount of water and ethyl acetate multiple times. Subsequently, the solvent was evaporated under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 20 - 1 / 10] to obtain 485 mg of a white solid, with a yield of 53%, melting point: 74 - 76 °C. 1 HNMR(400MHz,CDCl3)δ7.52(d,J=8.5Hz,1H),7.27(dd,J=8.5,2.6Hz,1H),7.19(d,J=2.6Hz,1H),6.07(ddd,J=17.2,10.4,5.0Hz,1H),5.43(d,J=17.9Hz,1H),5.36 - 5.32(m,1H),2.98(s,3H). 13 C NMR(100MHz,CDCl3)δ137.5,134.6,133.0,130.2,129.1,128.8,122.5,116.6,74.0,39.9.HRMS(ESI):calculated forC 10 H 12 BrNO3S[M+H] + :305.9794;Found:305.9792.

[0113] Example 33:

[0114]

[0115] 4.0 mg (0.006 mmol) of [Ir(cod)Cl]2 was added to a dry reaction tube, and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2j 61.4 mg, 0.2 mmol) were added, and after evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3aj (51.0 mg, 63% yield), melting point: 155 - 157 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 95 / 5, flow rate 2.0 mL / min, λ = 215 nm, t R = 8.66 min (minor) and 10.22 min (major). [α] D 20 : -21.4 (c = 0.25, CH2Cl2; 98% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.97 (dd, J = 8.4, 1.2 Hz, 2H), 7.67 - 7.62 (m, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.46 (d, J = 1.7 Hz, 1H), 7.13 (dd, J = 8.0, 1.7 Hz, 1H), 6.91 (dd, J = 8.0, 0.7 Hz, 1H), 6.01 (ddd, J = 16.8, 9.9, 8.5 Hz, 1H), 5.76 (d, J = 4.0 Hz, 1H), 5.23 (d, J = 9.9 Hz, 1H), 5.14 (d, J = 16.9 Hz, 1H), 3.80 (dd, J = 8.5, 4.0 Hz, 1H), 3.28 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.6, 136.5, 134.5, 133.5, 129.4, 129.2, 129.1, 127.1, 126.2, 122.7, 118.0, 115.6, 71.6, 49.8, 40.3. HRMS (ESI): calculated for C 18 H 16 BrNO3S [M+K] + : 443.9666; Found: 443.9662.

[0116] Example 34:

[0117]

[0118] 687 mg (3.0 mmol) of N-(2-formyl-5-methoxyphenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, followed by stirring for half an hour. Then, the reaction was allowed to proceed at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted multiple times with a small amount of water and ethyl acetate. Subsequently, the solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 20 - 1 / 10] to obtain 416 mg of a white solid, with a yield of 54% and a melting point of 54 - 56 °C. 1 H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.18 - 7.15 (m, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.07 (ddd, J = 17.1, 11.2, 4.8 Hz, 1H), 5.36 (d, J = 17.1 Hz, 1H), 5.30 - 5.25 (m, 2H), 3.78 (s, 3H), 3.26 (brs, 1H), 2.96 (s, 3H). 13 C NMR (100 MHz, CDCl3) δ 160.3, 142.8, 138.6, 137.4, 129.9, 115.6, 109.8, 106.6, 74.4, 55.6, 39.7. HRMS (ESI): calculated for C 11 H 15 NO4S [M + H] + : 258.0795; Found: 258.0793.

[0119] Example 35:

[0120]

[0121] [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) and the chiral ligand L1 (12.2 mg, 0.024 mmol) were added to a dry reaction tube, dissolved in 0.5 mL of dichloroethane, and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2k (51.6 mg, 0.2 mmol) were added. After evacuating and filling the reaction tube with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ka (46.4 mg, 65% yield), melting point: 136 - 138 °C; enantioselectivity: 92% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 8.54 min (minor) and 10.85 min (major). [α] D 20 : +89.8 (c = 0.25, CH2Cl2; 92% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.98 (d, J = 7.4 Hz, 2H), 7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.7 Hz, 2H), 7.21 (d, J = 8.2 Hz, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.80 (s, 1H), 6.03 (ddd, J = 16.9, 9.9, 8.6 Hz, 1H), 5.70 (d, J = 4.0 Hz, 1H), 5.21 (d, J = 9.9 Hz, 1H), 5.15 (d, J = 16.9 Hz, 1H), 3.83 (dd, J = 8.6, 4.0 Hz, 1H), 3.16 (s, 3H), 2.21 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.8, 160.8, 142.5, 137.3, 134.2, 133.6, 129.1, 129.0, 126.3, 122.1, 117.1, 108.5, 99.3, 72.0, 55.7, 49.5, 39.7. HRMS (ESI): calculated for C 19 H 19 NO4S [M + H] + : 358.1108; Found: 358.1107.

[0122] Example 36:

[0123]

[0124] 651.0 mg (3.0 mmol) of N-(2-formyl-6-fluorophenyl)methanesulfonamide was added to a 50 mL reaction tube, dissolved in tetrahydrofuran, and vinylmagnesium chloride was added dropwise at 0 °C under a vacuum and argon atmosphere, followed by stirring for half an hour. Then, the reaction mixture was allowed to react at room temperature for 8 h, quenched with saturated ammonium chloride solution, and the reaction solution was extracted several times with a small amount of water and ethyl acetate. Subsequently, the solvent was removed under reduced pressure, and the product was purified by silica gel column chromatography [eluent: V(ethyl acetate) / V(petroleum ether) = 1 / 20 - 1 / 10] to obtain 441.2 mg of a yellow solid with a yield of 60% and a melting point of 67 - 69 °C. 1 HNMR(400MHz,CDCl3)δ7.30 - 7.20(m,2H),7.12 - 7.07(m,2H),6.07(ddd,J=17.2,10.5,5.2Hz,1H),5.64 - 5.63(m,1H),5.44(d,J=17.2Hz,1H),5.28(d,J=10.5Hz,1H),3.28(brs,1H),3.14(s,3H). 13 C NMR(100MHz,CDCl3)δ157.7(d,J=246.8Hz),142.0,137.8,128.8(d,J=8.6Hz),124.5(d,J=3.2Hz),122.3(d,J=13.4Hz),116.2,115.6(d,J=20.9Hz),70.8,41.2. 19 F NMR(376MHz,CDCl3)δ - 120.67.HRMS(ESI):calculated forC 10 H 12 FNO3S[M + H] + :246.0595;Found:246.0597.

[0125] Example 37:

[0126]

[0127] [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) was added to a dry reaction tube, and the chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1a (98.5 mg, 0.5 mmol) and 2l (49.2 mg, 0.2 mmol) were added. After evacuating the reaction tube and filling it with argon (this operation was repeated three times), Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3al (48.3 mg, 70% yield), melting point: 126 - 128 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 5.07 min (minor) and 6.90 min (major). [α] D 20 : -14.1 (c = 0.25, CH2Cl2; 98% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 1.4 Hz, 2H), 7.65 - 7.63 (m, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.06 - 6.96 (m, 2H), 6.85 (d, J = 7.3 Hz, 1H), 6.11 (ddd, J = 16.9, 9.9, 8.4 Hz, 1H), 5.98 (d, J = 3.0 Hz, 1H), 5.25 (d, J = 9.9 Hz, 1H), 5.19 (d, J = 16.9 Hz, 1H), 3.86 (dd, J = 8.4, 3.0 Hz, 1H), 3.41 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 193.7, 150.2, 147.7, 135.2, 134.1 (d, J = 2.6 Hz), 133.1, 132.4, 128.0 (d, J = 1.3 Hz), 127.6 (d, J = 10.4 Hz), 123.9 (d, J = 6.9 Hz), 120.2 (d, J = 3.3 Hz), 116.4, 115.6 (d, J = 20.5 Hz), 70.9, 48.9 (d, J = 1.8 Hz), 41.7 (d, J = 8.1 Hz). 19 19F NMR (376 MHz, CDCl3) δ -123.8. HRMS (ESI): calculated for C 18 H 16 FNO3S [M + H] + : 346.0908; Found: 346.0905.

[0128] Example 38:

[0129]

[0130] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, then 1b (105.6 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol) are added. After evacuating and filling the reaction tube with argon (this operation is repeated three times), molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) are added, and the mixture is stirred in an oil bath at 45 °C for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3ba (37.5 mg, 55% yield), melting point: 71 - 73 °C; enantioselectivity: 86% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 12.83 min (minor) and 15.14 min (major). [α] D 20 : +83.5 (c = 0.25, CH2Cl2; 86% ee). 1 H NMR (400 MHz, CDCl3) δ 7.70 (dd, J = 8.1, 1.0 Hz, 1H), 7.44 (td, J = 7.6, 1.3 Hz, 1H), 7.33 - 7.29 (m, 2H), 7.28 - 7.26 (m, 2H), 7.08 (d, J = 7.5 Hz, 1H), 7.02 (td, J = 7.2, 1.4 Hz, 1H), 5.92 (ddd, J = 16.9, 10.0, 8.2 Hz, 1H), 5.62 (d, J = 4.6 Hz, 1H), 5.11 (d, J = 10.0 Hz, 1H), 5.00 (d, J = 16.9 Hz, 1H), 3.83 (dd, J = 8.2, 4.6 Hz, 1H), 3.24 (s, 3H), 2.48 (s, 3H). 1313C NMR (101 MHz, CDCl3) δ 198.5, 141.5, 139.7, 137.2, 134.5, 132.4, 132.3, 130.1, 129.3, 129.1, 125.9, 123.3, 117.4, 112.6, 72.9, 49.8, 39.9, 21.3. HRMS (ESI): calculated for C 19 H 19 NO3S [M+H] + : 342.1158; Found: 342.1158.

[0131] Example 39:

[0132]

[0133] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1c (116.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating and refilling the reaction tube with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3ca (53.4 mg, 74% yield), melting point: 80 - 82 °C; enantioselectivity: 94% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 6.83 min (minor) and 8.38 min (major). [α] D 20 : -12.6 (c = 0.25, CH2Cl2; 94% ee). 11H NMR (400 MHz, CDCl3) (δ, J = 1.6 Hz, 1H), 7.85 (d, J = 7.9 Hz, 1H), 7.63 - 7.58 (m, 1H), 7.45 (t, J = 7.9 Hz, 1H), 7.34 - 7.24 (m, 2H), 7.07 (d, J = 7.3 Hz, 1H), 7.02 (td, J = 7.3, 1.3 Hz, 1H) 6.03 (ddd, J = 16.9, 9.9, 8.6 Hz, 1H), 5.65 (d, J = 4.3 Hz, 1H), 5.25 (d, J = 9.9 Hz, 1H), 5.16 (d, J = 16.9 Hz, 1H), 3.86 (dd, J = 8.6, 4.3 Hz, 1H), 3.25 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 193.9, 141.2, 136.7, 135.4, 135.3, 134.0, 130.2, 129.9, 129.2, 127.1, 125.9, 123.3, 117.9, 112.4, 71.2, 50.2, 39.7. HRMS (ESI): calculated for C 18 H 16 ClNO3S [M + H] + : 362.0612; Found: 362.0611.

[0134] Example 40:

[0135]

[0136] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1d (112.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3da (39.8 mg, 56% yield), melting point: 103 - 105 °C; enantioselectivity: 93% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 4.80 min (minor) and 6.36 min (major). [α] D 20 : -12.6 (c = 0.25, CH2Cl2; 93% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 2H), 7.29 (dd, J = 3.4, 1.1 Hz, 1H), 7.27 - 7.25 (m, 2H), 7.05 (d, J = 7.0 Hz, 1H), 6.99 (td, J = 7.4, 1.5 Hz, 1H), 6.04 (ddd, J = 16.9, 10.0, 8.6 Hz, 1H), 5.73 (d, J = 3.9 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H), 5.14 (d, J = 16.9 Hz, 1H), 3.84 (dd, J = 8.6, 3.9 Hz, 1H), 3.28 (s, 3H), 2.38 (s, 6H). 13 13C NMR (101 MHz, CDCl3) δ 7.59 (s, 2H), 7.29 (dd, J = 3.4, 1.1 Hz, 1H), 7.27 - 7.25 (m, 2H), 7.05 (d, J = 7.0 Hz, 1H), 6.99 (td, J = 7.4, 1.5 Hz, 1H), 6.04 (ddd, J = 16.9, 10.0, 8.6 Hz, 1H), 5.73 (d, J = 3.9 Hz, 1H), 5.22 (d, J = 10.0 Hz, 1H), 5.14 (d, J = 16.9 Hz, 1H), 3.84 (dd, J = 8.6, 3.9 Hz, 1H), 3.28 (s, 3H), 2.38 (s, 6H). HRMS (ESI): calculated for C 20 H 21 NO3S [M + H] + : 356.1315; Found: 356.1313.

[0137] Example 41:

[0138]

[0139] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1e (105.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol) are added. After evacuating and refilling the reaction tube with argon (this operation is repeated three times), molecular sieve (50.0 mg), 1.5 mL of dichloroethane, and trifluoroacetic acid (68.4 mg, 0.6 mmol) are added, and the mixture is stirred in an oil bath at 45 °C for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3ea (51.2 mg, 75% yield), melting point: 108 - 110 °C; enantioselectivity: 87% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 4.02 min (minor) and 6.16 min (major). [α] D 20 : -10.6 (c = 0.25, CH2Cl2; 87% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.98 (dd, J = 8.4, 1.2 Hz, 2H), 7.25 (d, J = 8.8 Hz, 1H), 7.53 - 7.49 (m, 2H), 7.26 - 7.23 (m, 1H), 6.82 (dd, J = 8.7, 2.5 Hz, 1H), 6.63 (d, J = 2.2 Hz, 1H), 6.04 (ddd, J = 16.9, 10.0, 8.4 Hz, 1H), 5.67 (d, J = 4.1 Hz, 1H), 5.23 (d, J = 10.0 Hz, 1H), 5.16 (d, J = 17.7 Hz, 1H), 3.84 (dd, J = 8.4, 4.1 Hz, 1H), 3.75 (s, 3H), 3.20 (s, 3H). 1313C NMR (101 MHz, CDCl3) δ 194.8, 160.8, 142.5, 137.3, 134.1, 133.7, 129.1, 128.9, 126.3, 122.1, 117.1, 108.5, 99.3, 72.0, 55.7, 49.5, 39.7. HRMS (ESI): calculated for C 19 H 19 NO3S [M+H] + : 342.1158; Found: 342.1156.

[0140] Example 42:

[0141]

[0142] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, then add 1f (132.2 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating and filling the reaction tube with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3fa (47.4 mg, 60% yield), melting point: 79 - 81 °C; enantioselectivity: 84% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 6.72 min (minor) and 10.13 min (major). [α] D 20 : +62.0 (c = 0.25, CH2Cl2; 84% ee). 11H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H), 7.35 - 7.26 (m, 2H), 7.08 (d, J = 7.2 Hz, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.03 (ddd, J = 16.9, 9.9, 8.6 Hz, 1H), 5.68 (d, J = 4.7 Hz, 1H), 5.25 (d, J = 9.9 Hz, 1H), 5.16 (d, J = 16.9 Hz, 1H), 3.88 (dd, J = 8.6, 4.7 Hz, 1H), 3.24 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.3, 141.1, 136.6, 135.2 (q, J = 32.9 Hz), 129.9, 129.4, 129.2, 126.0 (q, J = 3.7 Hz), 125.9, 123.5, 123.4 (q, J = 271 Hz), 118.0, 112.5, 71.3, 50.1, 39.5. 19 19F NMR (376 MHz, CDCl3) δ -63.2. HRMS (ESI): calculated for C 19 H 16 F3NO3S [M + H] + : 396.0876; Found: 396.0876.

[0143] Example 43:

[0144]

[0145] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, then add 1 g (93.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid

[0146] Product 3ga (45.0 mg, 71% yield), melting point: 110 - 112 °C; enantioselectivity: 99% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 70 / 30, flow rate 2.0 mL / min, λ = 215 nm, t R = 10.29 min (minor) and 12.92 min (major). [α] D 20 : -40.7 (c = 0.25, CH2Cl2; 99% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.62 - 7.61 (m, 1H), 7.28 - 7.25 (m, 2H), 7.23 - 7.19 (m, 1H), 7.03 (d, J = 7.4 Hz, 1H), 6.96 (td, J = 7.4, 1.1 Hz, 1H), 6.53 (dd, J = 3.6, 1.7 Hz, 1H), 5.98 (ddd, J = 17.0, 10.0, 8.0 Hz, 1H), 5.37 (d, J = 4.8 Hz, 1H), 5.15 (d, J = 10.0 Hz, 1H), 5.08 (d, J = 17.0 Hz, 1H), 3.88 (dd, J = 8.0, 4.8 Hz, 1H), 3.13 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 184.0, 150.1, 147.8, 141.4, 137.1, 130.2, 129.1, 125.9, 123.4, 120.0, 117.6, 112.8, 112.6, 71.2, 50.3, 39.3. HRMS (ESI): calculated for C 16 H 15 NO4S [M + H] + : 318.0795; Found: 318.0794.

[0147] Example 44:

[0148]

[0149] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane, stirred at room temperature for 10 minutes, then add 1h (101.1 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a white solid product 3ha (43.3 mg, 65% yield), melting point: 129 - 131 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 70 / 30, flow rate 2.0 mL / min, λ = 215 nm, t R = 4.43 min (minor) and 6.18 min (major). [α] D 20 : -65.7 (c = 0.25, CH2Cl2; 98% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.82 (d, J = 3.8 Hz, 1H), 7.75 (d, J = 4.9 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.30 - 7.26 (m, 1H), 7.19 - 7.17 (m, 1H), 7.09 (d, J = 7.3 Hz, 1H), 7.03 (t, J = 7.3 Hz, 1H), 6.07 - 5.98 (m, 1H), 5.46 (d, J = 4.7 Hz, 1H), 5.24 (d, J = 9.9 Hz, 1H), 5.18 (d, J = 16.9 Hz, 1H), 3.98 (dd, J = 8.3, 4.7 Hz, 1H), 3.21 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 188.3, 141.3, 140.4, 136.9, 135.4, 133.6, 130.2, 129.1, 128.6, 125.9, 123.4, 117.8, 112.5, 72.0, 50.9, 39.3. HRMS (ESI): calculated for C 16 H 15 NO3S2 [M + H] +: 334.0566; Found: 334.0569.

[0150] Example 45:

[0151]

[0152] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1i (80.5.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain a yellow oil product 3ia (32.9 mg, 56% yield); enantioselectivity: 88% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak IA column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 4.03 min (minor) and 4.58 min (major). [α] D 20 : -72.2 (c = 0.25, CH2Cl2; 88% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.1 Hz, 1H), 7.30 - 7.26 (m, 1H), 7.14 (d, J = 7.5 Hz, 1H), 7.08 (td, J = 7.5, 1.0 Hz, 1H), 5.96 (ddd, J = 17.4, 10.0, 7.6 Hz, 1H), 5.25 (d, J = 10.0 Hz, 1H), 5.17 (d, J = 16.9 Hz, 1H), 4.60 (d, J = 5.4 Hz, 1H), 3.93 - 3.90 (m, 1H), 3.00 (s, 3H), 2.76 - 2.68 (m, 1H), 2.63 - 2.55 (m, 1H), 1.67 - 1.58 (m, 3H), 0.92 (t, J = 7.4 Hz, 3H). 1313C NMR (101 MHz, CDCl3) δ 207.1, 141.1, 137.5, 130.8, 129.1, 125.9, 124.2, 117.8, 113.9, 74.4, 48.8, 41.1, 37.6, 16.6, 13.6. HRMS (ESI): calculated for C 15 H 19 NO3S [M+H] + : 294.1158; Found: 294.1158.

[0153] Example 46:

[0154]

[0155] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) was dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then, 1j (80.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol) were added. After evacuating and refilling the reaction tube with argon (this operation was repeated three times), molecular sieve (50.0 mg), 1.5 mL of dichloroethane, and trifluoroacetic acid (68.4 mg, 0.6 mmol) were added, and the mixture was stirred in an oil bath at 45 °C for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ja (30.3 mg, 52% yield), melting point: 124 - 126 °C; enantioselectivity: 94% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak IA column, n-hexane / i-PrOH = 95 / 5, flow rate 2.0 mL / min, λ = 215 nm, t R = 19.70 min (minor) and 21.32 min (major). [α] D 20 : -60.4 (c = 0.25, CH2Cl2; 94% ee). 1HNMR(400MHz,CDCl3)δ7.39(d,J=8.1Hz,1H),7.30 - 7.25(m,1H),7.15(d,J=7.4Hz,1H),7.07(td,J=7.4,1.0Hz,1H),5.99(ddd,J=16.9,10.0,7.7Hz,1H),5.26 - 5.20(m,2H),4.79(d,J=5.4Hz,1H),4.04 - 4.07(m,1H),3.06(s,3H),2.26(tt,J=7.8,4.6Hz,1H),1.15 - 1.10(m,2H),1.08 - 1.04(m,1H),1.02 - 0.96(m,1H). 13 C NMR(101MHz,CDCl3)δ206.5,141.2,137.4,130.8,129.0,125.9,124.0,117.6,113.66,75.0,48.9,37.9,17.3,12.24,12.20.HRMS(ESI):calculated forC 15 H 17 NO3S[M + H] + :292.1002;Found:292.1002.

[0156] Example 47:

[0157]

[0158] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1k (80.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating and filling the reaction tube with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ka (35.3 mg, 53% yield), melting point: 87 - 89 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak ID column, n - hexane / i - PrOH = 95 / 5, flow rate 2.0 mL / min, λ = 215 nm, tR = 10.70 min (minor) and 13.58 min (major). [α] D 20 : -25.9 (c = 0.25, CH2Cl2; 98% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.1 Hz, 1H), 7.28 - 7.24 (m, 1H), 7.11 (d, J = 7.6 Hz, 1H), 7.04 (td, J = 7.4, 1.1 Hz, 1H), 5.97 (ddd, J = 16.9, 10.0, 8.0 Hz, 1H), 5.24 - 5.17 (m, 2H), 4.86 (d, J = 5.2 Hz, 1H), 3.85 (dd, J = 8.0, 5.2 Hz, 1H), 3.08 (s, 3H), 2.75 - 2.68 (m, 1H), 1.91 - 1.79 (m, 4H), 1.69 (d, J = 11.1 Hz, 1H), 1.53 - 1.45 (m, 1H), 1.33 - 1.25 (m, 4H). 13 13C NMR (101 MHz, CDCl3) δ 209.1, 141.3, 137.7, 130.4, 129.0, 125.9, 123.6, 117.4, 113.2, 72.9, 48.9, 47.4, 38.6, 29.1, 27.9, 25.72, 25.70, 25.3. HRMS (ESI): calculated for C 18 H 23 NO3S [M + H] + : 334.1471; Found: 334.1470.

[0159] Example 48:

[0160]

[0161] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1l (111.2 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add Molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol) were placed in an oil bath at 45 °C and stirred for 8 h. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3la (40.2 mg, 54% yield), melting point: 112 - 114 °C; enantioselectivity: 94% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak IA column, n-hexane / i-PrOH = 90 / 10, flow rate 2.0 mL / min, λ = 215 nm, t R = 9.92 min (minor) and 12.35 min (major). [α] D 20 : -23.5 (c = 0.25, CH2Cl2; 94% ee). 1 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 16.0 Hz, 1H), 7.59 - 7.56 (m, 2H), 7.43 - 7.37 (m, 4H), 7.29 (t, J = 7.7 Hz, 1H), 7.15 (d, J = 7.5 Hz, 1H), 7.10 - 7.06 (m, 2H), 6.03 (ddd, J = 17.0, 10.0, 7.8 Hz, 1H), 5.27 (d, J = 10.0 Hz, 1H), 5.21 (d, J = 17.0 Hz, 1H), 4.93 (d, J = 5.3 Hz, 1H), 4.06 - 4.03 (m, 1H), 3.09 (s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 194.9, 145.7, 141.2, 137.4, 134.2, 131.1, 130.9 129.1 129.0, 128.8 125.9, 124.0 121.0, 117.8, 113.8, 73.8, 49.2, 38.0. HRMS (ESI): calculated for C 20 H 19 NO3S [M + H] + : 354.1158; Found: 354.1156.

[0162] Example 49:

[0163]

[0164] Add [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol) to a dry reaction tube. The chiral ligand L1 (12.2 mg, 0.024 mmol) is dissolved in 0.5 mL of dichloroethane and stirred at room temperature for 10 minutes. Then add 1m (82.0 mg, 0.5 mmol) and 2a (45.6 mg, 0.2 mmol). After evacuating the reaction tube and filling it with argon (this operation is repeated three times), add molecular sieve (50.0 mg), 1.5 mL of dichloroethane and trifluoroacetic acid (68.4 mg, 0.6 mmol), and place it in an oil bath at 45 °C and stir for 8 h. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:50 - 1:10) to obtain the white solid product 3ma (38.4 mg, 65% yield), melting point: 112 - 114 °C; enantioselectivity: 98% ee, diastereoselectivity: >19:1; HPLC conditions: Daicel Chiralpak OD-H column, n-hexane / i-PrOH = 95 / 5, flow rate 2.0 mL / min, λ = 215 nm, t R = 10.99 min (major) and 11.95 min (minor). [α] D 20 :+47.8 (c = 0.25, CH2Cl2; 98% ee). 1 H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 7.9 Hz, 2H), 7.7.29 - 7.24 (m, 1H), 7.13 (d, J = 7.5 Hz, 1H), 7.05 (td, J = 7.3, 1.3 Hz, 1H), 5.95 (ddd, J = 17.0, 10.0, 7.7 Hz, 1H) 5.24 - 5.18 (m, 2H), 4.70 (d, J = 5.3 Hz, 1H), 4.27 (qd, J = 7.1, 4.8 Hz, 2H), 4.02 - 3.98 (m, 1H), 3.15 (s, 3H), 1.31 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 170.7, 141.0, 136.9, 130.3, 129.0, 125.6, 123.5, 117.6, 113.0, 68.4, 62.0, 50.1, 38.9, 14.2. HRMS (ESI): calculated for C 14 H 17 NO4S [M + H] + : 296.0951; Found: 296.0949.

Claims

1. A method for highly stereoselective synthesis of 3-vinylindol-2-one derivatives, characterized in that: An iridium catalyst and a chiral ligand are added to a reaction vessel, and a solvent is added and stirred at room temperature. Then, 1-(2-aminophenyl)prop-2-en-1-ol derivative and sulfoxonium ylide are added. Under argon protection, an additive, an acid, and a solvent are added and stirred at a certain temperature for a certain time to obtain a chiral 3-vinylindol-2-one derivative; ； R 1 is Ts, Ns, Ms, 4-MeO, C6H4SO2; R 2 is H, 3-F, 4-Br, 4-MeO, 5-Me, 5-MeO, 5-Cl, 6-Cl, 6-Me; Ar is Ph, 2-MeC6H4, 3, 5-Me2C6H3, 3-ClC6H4, 4-MeC6H4, 4-CF3C6H4, n-Pr, , , , , , EtO; The iridium catalyst is: [Ir(cod)Cl]2; The chiral ligand is as follows: ; The additive is one of 3Å molecular sieve, 4Å molecular sieve, and 5Å molecular sieve; The acid is: trifluoroacetic acid, trichloroacetic acid.

2. The method for highly stereoselectively synthesizing 3-vinylindole-2-one derivatives according to claim 1, wherein, The molar ratio of the iridium catalyst, chiral ligand, 1-(2-aminophenyl)prop-2-en-1-ol derivative, and sulfoxonium ylide is: 0.003~0.006:0.012~0.024:1:1~2.

5.

3. The method for highly stereoselectively synthesizing 3-vinylindole-2-one derivatives according to claim 1, characterized in that, The solvent is one of toluene, tetrahydrofuran, dichloroethane, chloroform, carbon tetrachloride, acetonitrile, hexafluoroisopropanol, methylcyclohexane, cyclohexane, cyclopentane, n-hexane, methyl tert-butyl ether, and diethyl ether.

4. The method for highly stereoselective synthesis of 3-vinylindole-2-one derivatives according to claim 1, characterized in that, The reaction temperature is: 25~60 °C, and the reaction time is 8 - 72 h.

5. The method for highly stereoselective synthesis of 3-vinylindole-2-one derivatives according to claim 1, characterized in that, The equivalent ratio of acid to 1-(2-aminophenyl)prop-2-en-1-ol derivative is 1~4:1.

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