Method for synthesizing axially chiral sulfonamide biaryl phenol derivative with high stereoselectivity

Abstract

The invention belongs to the technical field of organic chemical synthesis, and particularly discloses a method for synthesizing an axially chiral sulfonamide biaryl diphenol derivative with high stereoselectivity. The invention relates to a method for synthesizing an axial chiral sulfonamide biaryl diphenol derivative with high enantioselectivity by using chiral phosphoric acid to catalyze a biaryl diphenol derivative and a sulfonamide derivative. The method has the advantages that raw materials used in the synthesis method are cheap and easy to prepare, reaction conditions are mild, atom economy is high, the substrate application range is wide, and regioselectivity and enantioselectivity are good.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a reaction of a biaryl diphenol derivative and a sulfonamide derivative to synthesize an axially chiral sulfonamide biaryl diphenol derivative with high enantioselectivity. Background Art

[0002] As an important type of skeleton structure, biaryl polyphenol compounds are widely present in natural products, bioactive molecules and drugs. Most natural products and their isomers with this skeleton have good physiological activities, such as the famous antibiotic heptapeptide vancomycin, the drug dimer Michellamine B for the treatment of HIV, Korupensamine A with antimalarial properties and its axial chiral isomer Korupensamine B, and ellagic acid with preventive and therapeutic effects on various diseases such as tumors, diabetes, cardiovascular diseases and neurodegenerative diseases. Therefore, biaryl polyphenol compounds have attracted more and more attention from researchers. The synthetic methods for forming axial chiral biaryls have been reported. This strategy has only been studied in a limited number of catalytic methods. Hayashi's group pioneered the synthesis of biaryl axial chiral compounds using asymmetric catalytic coupling (J.Am.Chem.Soc.,1995,117,9101-9102). Subsequently, Akiyama and his colleagues also developed a new chiral phosphoric acid-catalyzed enantioselective bromination as a means of constructing multi-substituted diaryl compounds (J.Am.Chem.Soc.,2013,135,3964-3970). In 2023, Martin Oestreich and his colleagues reported a silylation reaction guided by List's counteranion to achieve asymmetric silylation of axial chiral aromatic phenols. (Angew.Chem.Int.Ed.2023,62e202304475.).

[0003] Sulfonamide, as a kind of pharmacological group with a wide range of biological activities, has shown excellent activity and great development value in the fields of medicine and pesticides. It was first developed as an antibacterial drug, but it also has good performance in herbicide, anticancer, antitumor, antidiabetic and other aspects (He Shichao et al., Chinese Science: Chemistry, 2016, 46(09): 823-847). The research and development of synthetic modification of this type of compound has a very broad application prospect. At present, a large number of structurally modified sulfonamide antibacterial drugs have entered the clinic.

[0004] According to previous studies, we adopted a desymmetric strategy and used chiral phosphoric acid to catalyze the high enantioselective synthesis of axially chiral sulfonamide-modified biaryl diphenol derivatives with biaryl diphenol derivatives and sulfonamide derivatives. The raw materials used in this method are cheap and easy to prepare, the reaction conditions are mild, the atom economy is high, the substrate application range is wide, and the regional and enantioselectivity are good. In addition, compared with previous studies, a new active pharmacological group sulfonamide group is introduced, and active compounds with both biaryl polyphenol and sulfonamide skeletons are synthesized, which greatly enriches the axially chiral biaryl polyphenol and sulfonamide covalent potential drug molecule library. Because of the electrophilic groups they have, they can also be used as active sites for further derivatization of covalently bound drugs, and have broad application prospects. Summary of the invention

[0005] The invention provides a method for synthesizing an axial chiral sulfonamide biaryl diphenol derivative with high enantioselectivity by using chiral phosphoric acid as a catalyst to catalyze a biaryl diphenol derivative and a sulfonamide derivative.

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

[0007]

[0008] Wherein, Ar is any one of the following substituents:

[0009]

[0010] R is any of the following substituents:

[0011]

[0012] A method for synthesizing an axially chiral sulfonamide biaryl diphenol derivative comprises the following steps: adding a biaryl diphenol derivative, a sulfonamide derivative and a chiral phosphoric acid catalyst into a dry reaction tube, then adding a certain amount of solvent into the reaction tube, filling with argon gas, stirring at a certain temperature, completing the reaction after a period of time, and purifying the residue by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:1) to obtain the axially chiral sulfonamide biaryl diphenol derivative.

[0013] The specific structural formula of the biaryl diphenol derivative is as follows:

[0014]

[0015] The structural formula of the sulfonamide derivative is as follows:

[0016] Ts is p-toluenesulfonyl; iPr is isopropyl; Bn is benzyl; Et is ethyl. The chiral phosphoric acid catalyst used is one of the following:

[0017]

[0018] Among them, preferred chiral phosphoric acids are CPA1, CPA2, CPA8, and CPA9.

[0019] The solvent for the reaction is: dichloromethane, dichloroethane, toluene, chloroform, ethylene glycol dimethyl ether, etc. Among them, the preferred solvent is dichloromethane.

[0020] The molar ratio of the biaryl diphenol derivative, the sulfonamide derivative and the chiral phosphoric acid in the reaction is: 2-1:2-1.1:0.05-0.01, and the preferred molar ratio is: 1:1.1:0.025.

[0021] When the biaryl diphenol derivative is 1 equivalent, the concentration of the reaction solution is 0.025-0.10 mol / L, preferably 0.05 mol / L.

[0022] The reaction temperature is: -20-25°C, the reaction time is 4-72h; the preferred reaction temperature is 0°C.

[0023] Benefits and advantages

[0024] The present invention designs a method for synthesizing an axially chiral sulfonamide biaryl diphenol derivative with high enantioselectivity by using a biaryl diphenol derivative and a sulfonamide derivative under the catalysis of chiral phosphoric acid. A simple approach is provided for synthesizing optically pure covalent potential drug compounds containing both sulfonamide and biaryl polyphenol mother nuclei. Specifically disclosed is a method for synthesizing an optically pure axially chiral sulfonamide biaryl diphenol derivative. The present invention uses a method for synthesizing an axially chiral sulfonamide substituted biaryl diphenol derivative with high enantioselectivity by using a biaryl diphenol derivative and a sulfonamide derivative under the catalysis of chiral phosphoric acid.

[0025] The method of the present invention has the following advantages: the raw materials used in the synthesis method are cheap and easy to prepare, the reaction conditions are mild, the atom economy is high, the substrate has a wide application range, and the regional and enantioselectivity are good. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 3aa obtained in Example 4 1 H-NMR (nuclear magnetic resonance spectroscopy);

[0027] Figure 2 3aa obtained in Example 4 13 C-NMR (Nuclear Magnetic Carbon Spectroscopy);

[0028] Figure 3 HRMS (high resolution mass spectrometry) of 3aa obtained in Example 4;

[0029] Figure 4This is the HPLC (high performance liquid chromatography) of 3aa obtained in Example 4. DETAILED DESCRIPTION

[0030] The present invention will be further described below by specific examples, but the present invention is not limited to the following examples. Unless otherwise defined, the technical terms used in the following examples have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. The test reagents used in the following examples, unless otherwise specified, are all conventional reagents, which can be purchased on the market or synthesized according to conventional methods in the art; the experimental methods, unless otherwise specified, are all conventional methods.

[0031] Example 1

[0032]

[0033] Under nitrogen protection, 2,4-dimethylbromobenzene (1.0 g, 5.4 mmol) was dissolved in dioxane / water (30 mL / 6 mL), and then 2,6-dimethoxyphenylboronic acid (1.78 g, 9.7 mmol), Pd(PPh3)4 (0.31 g, 0.27 mmol), and K2CO3 (2.98 g, 21.56 mmol) were added. The reaction solution was refluxed and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature, H2O (30 mL) was added to the solution to quench, and extracted with ethyl acetate (3×25 mL). The organic layer was washed with brine, dried over sodium persulfate, filtered, and concentrated to dryness. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 200: 1-70: 1) to obtain a colorless oil 1j (1 g, 77%). R f (petroleum ether / ethyl acetate=50:1)=0.4.

[0034] The above product was dissolved in dry dichloromethane, BBr3 was slowly added at 0°C, and stirred at room temperature overnight. H2O (20 mL) was slowly added to the reaction solution at 0°C, and extracted with DCM (3×10 mL). The organic layers were combined, dried over sodium persulfate, filtered, and concentrated to dryness. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 20:1-7:1) to obtain an orange-red gum 1j (0.7 g, 77%). f (petroleum ether / ethyl acetate=5:1)=0.5. 1 H NMR (400MHz, Acetone-d6) δ7.55 (s, 2H), 7.05 (s, 1H), 7.04-6.97 (m, 3H), 6.48 (d, J = 8.0Hz, 2H), 2.29 (s, 3H), 2.10 (s, 3H). 13CNMR(101MHz,Acetone-d6)δ156.4,138.7,137.5,132.1,131.6,131.5,129.3,127.2,116.8,107.8,21.3,20.1.

[0035] Example 2

[0036]

[0037] Under nitrogen protection, 2,5-dimethylbromobenzene (1.5 g, 8 mmol) was dissolved in dioxane / water (30 mL / 6 mL), and then 2,6-dimethoxyphenylboronic acid (2.6 g, 14.4 mmol), Pd(PPh3)4 (0.46 g, 0.4 mmol), and K2CO3 (4.4 g, 32 mmol) were added. The reaction solution was refluxed and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature, H2O (30 mL) was added to the solution to quench, and extracted with ethyl acetate (3×25 mL). The organic layer was washed with brine, dried over sodium persulfate, filtered, and concentrated to dryness. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 200: 1-70: 1) to obtain a colorless oil (1.5 g, 79%). f (petroleum ether / ethyl acetate=50:1)=0.5.

[0038] The above product was dissolved in dry dichloromethane, BBr3 was slowly added at 0°C, and stirred at room temperature overnight. H2O (20 mL) was slowly added to the reaction solution at 0°C, and extracted with DCM (3×10 mL). The organic layers were combined, dried over sodium persulfate, filtered, and concentrated to dryness. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 20:1-7:1) to obtain an orange-red gum 1k (1.1 g, 80%). f (petroleum ether / ethyl acetate=50:1)=0.6. 1 H NMR (400MHz, Acetone-d6) δ7.56(s,2H),7.12(d,J=8.0Hz,1H),7.04-6.97(m,2H),6.96(s,1H),6.48(d,J=8.4Hz,2H),2.27(s,3H),2.09(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.3,135.8,135.4,134.6,132.7,130.6,129.3,129.0,117.0,107.9,21.2,19.7.

[0039] Example 3

[0040]

[0041] Under nitrogen protection, 2,5-dimethylbromobenzene (1.0 g, 5.4 mmol) was dissolved in dioxane / water (30 mL / 6 mL), and then 2,6-dimethoxyphenylboronic acid (1.8 g, 9.7 mmol), Pd(PPh3)4 (0.31 g, 0.27 mmol), and K2CO3 (2.98 g, 21.56 mmol) were added. The reaction solution was refluxed and stirred overnight. After the reaction was completed, the mixture was cooled to room temperature, H2O (30 mL) was added to the solution to quench, and extracted with ethyl acetate (3×25 mL). The organic layer was washed with brine, dried over sodium persulfate, filtered, and concentrated to dryness. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 200: 1-70: 1) to obtain a white solid (0.8 g, 61%). f (petroleum ether / ethyl acetate=50:1)=0.5.

[0042] The above product was dissolved in dry dichloromethane, BBr3 was slowly added at 0°C, and stirred at room temperature overnight. H2O (20 mL) was slowly added to the reaction solution at 0°C, and extracted with DCM (3×10 mL). The organic layers were combined, dried over sodium persulfate, filtered, and concentrated to dryness. The crude product was purified by column chromatography (petroleum ether: ethyl acetate = 20:1-7:1) to obtain a white solid 1n (0.6 g, 76%). f (petroleum ether / ethyl acetate=50:1)=0.6. 1 H NMR (400MHz, Acetone-d6) δ7.55(s,2H),7.06-7.03(m,1H),7.01(s,1H),7.01-6.96(m,2H),6.48(d,J=8.0Hz,2H),2.29(s,3H),2.10(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.4,138.7,137.5,132.1,131.6,131.5,129.3,127.2,116.8,107.8,21.3,20.1.

[0043] Example 4

[0044]

[0045] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.4 mg, 86%, 95% ee).

[0046] Example 5

[0047] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA2 (1.5 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (24.6 mg, 80%, 80% ee).

[0048] Example 6

[0049] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA3 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (19.4 mg, 63%, 38% ee).

[0050] Example 7

[0051] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA4 (1.5 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.1 mg, 85%, 2% ee).

[0052] Example 8

[0053] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA5 (1.7 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (15.4 mg, 50%, 10% ee).

[0054] Example 9

[0055] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA6 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (20.0 mg, 65%, 40% ee).

[0056] Example 10

[0057] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA7 (1.4 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (27.7 mg, 90%, 2% ee).

[0058] Embodiment 11

[0059] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA8 (1.5 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (24.6 mg, 80%, 80% ee).

[0060] Example 12

[0061] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA9 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.4 mg, 86%, 93% ee).

[0062] Embodiment 13

[0063] A biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), a sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), and chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol) were added to a dry reaction tube, and then 1 mL of dry toluene was added, and stirred at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (basic silica gel, eluent: EtOAc / PE = 1:3-1:1) to obtain an off-white solid 3aa (28.5 mg, 79%, 92% ee).

[0064] Embodiment 14

[0065] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCE, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.4 mg, 86%, 93% ee).

[0066] Embodiment 15

[0067] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry chloroform, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (27.7 mg, 90%, 80% ee).

[0068] Example 16

[0069] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 25 ° C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE = 1:3-1:1) to obtain an off-white solid 3aa (23.4 mg, 76%, 92% ee).

[0070] Embodiment 17

[0071] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol), and then add 1 mL of dry DCM, and stir at 10°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (25.5 mg, 83%, 95% ee).

[0072] Embodiment 18

[0073] Add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol) to a dry reaction tube, then add 1 mL of dry DCM, and stir at -10 ° C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (basic silica gel, eluent: EtOAc / PE = 1:3-1:1) to obtain an off-white solid 3aa (26.1 mg, 85%, 95% ee)

[0074] Embodiment 19

[0075] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0025 mmol), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (25.8 mg, 84%, 95% ee).

[0076] Embodiment 20

[0077] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (0.9 mg, 0.00125 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.4 mg, 86%, 95% ee).

[0078] Embodiment 21

[0079] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (0.4 mg, 0.0005 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (23.4 mg, 76%, 95% ee).

[0080] Embodiment 22

[0081] To a dry reaction tube, add biaryl diphenol derivative (1a) (10 mg, 0.05 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (1.9 mg, 0.0125 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 48 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.1 mg, 85%, 95% ee).

[0082] Embodiment 23

[0083] To a dry reaction tube, add biaryl diphenol derivative (1a) (20 mg, 0.1 mmol), sulfonamide derivative (2a) (22.8 mg, 0.055 mmol), chiral phosphoric acid CPA1 (0.9 mg, 0.00125 mmol), and then add 1 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (basic silica gel, eluent: EtOAc / PE=1:3-1:1) to obtain an off-white solid 3aa (26.1 mg, 85%, 95% ee).

[0084] Embodiment 24

[0085]

[0086] To a dry reaction tube, add biaryl diphenol derivative (1a) (20 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3aa (53.4 mg, 87%), mp: 146-148°C. f (EtOAc / PE=1:2)=0.3.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =11.145min(major),13.793min(minor),95%ee. 1 H NMR(400MHz,Chloroform-d)δ7.66(d,J=8.0Hz,2H),7.59(d,J=8.0Hz,2H),7.41-7.35(m,2H),7.35-7.30(m,1H),7.28(s,2H),7.26-7.16(m,6 H),6.99(d,J=8.8Hz,2H),6.78(d,J=8.8Hz,1H),6.45(d,J=8.8Hz,1H),6.22(brs,1H),4.92(brs,1H),2.45(s,3H),2.38(s,3H),2.10(s,3H). 13 C NMR(101MHz,Chloroform-d)δ154.0,151.9,144.4,144.2,138.9,138.3,136.0,135.74,135.66,131.2,130.8,130.1,129. 9,129.8,129.7,129.5,128.23,128.15,127.3,126.9,121.5,120.4,116.4,107.8,21.7,21.6,19.5.HRMS(ESI)m / z:[M+Na] + Calculated for C 33 H 30 N2NaO6S2637.1437; Found 637.1439.

[0087] Embodiment 25

[0088]

[0089] To a dry reaction tube, add biaryl diphenol derivative (1b) (22.1 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:1) to obtain an off-white solid 3ba (56.7 mg, 89%), mp: 207-209°C. f (EtOAc / PE=1:2)=0.2.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =16.642min(major),20.398min(minor),90%ee.[α] D 25 :-19.300(c=0.2,CH2Cl2). 1 H NMR (400MHz, DMSO-d6) δ10.35(s,1H),9.57(s,1H),8.60(s,1H),7.66(d,J=8.0Hz,2H),7.48(d,J=8.4Hz,2H),7.44(d,J=4.0Hz,1H),7.34(dd,J =8.0,1.6Hz,4H),7.29(d,J=8.8Hz,4H),7.14(s,1H),7.01(d,J=8.8Hz, 2H),6.77(s,1H),6.32(dd,J=8.8,1.6Hz,1H),2.39(s,3H),2.33(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.8,154.3,144.8,144.6,139.1,138.0,137.8,137.5,135.8,134.2,133.9,131.2,130 .5,130.4,130.1,129.9,129.12,129.08,128.0,127.5,121.3,121.0,116.2,107.8,21.6,21.5.HRMS(ESI)m / z:[M+K] +Calculated for C 32 H 27 35 ClKN2O6S2673.0631; Found 673.0632.

[0090] Embodiment 26

[0091]

[0092] To a dry reaction tube, add biaryl diphenol derivative (1c) (26.4 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:1) to obtain an off-white solid 3ca (61.0 mg, 90%), mp: 126-128°C. f (EtOAc / PE=1:2)=0.3.HPLC(IA, i-PrOH / n-hexane=65 / 35, flow rate=1mL / min, λ=215nm)t R =17.291min(major),23.308min(minor),93%ee.[α] D 25 :-35.800(c=0.2,CH2Cl2). 1 H NMR (400MHz, DMSO-d6) δ10.35(brs,1H),9.58(brs,1H),8.58(brs,1H),7.67(d,J=8.0Hz,2H),7.62(d,J=8.0Hz,1H),7.51(d,J=8.4Hz,2H),7.39-7.31 (m,6H),7.30(s,1H),7.24-7.19(m,1H),7.19-7.07(m,1H),7.03(d,J=8.8H z,2H),6.89-6.69(m,1H),6.33(d,J=8.8Hz,1H),2.37(s,3H),2.32(s,3H). 13C NMR (101MHz, DMSO-d6) δ155.7,153.1,143.5,143.4,137.3,136.7,136.6,136.2,135.7,132.8,132.0,129.8,129. 6,129.5,128.9,127.9,127.2,127.1,126.7,125.0,119.8,119.3,116.8,106.3,21.1,21.0.HRMS(ESI)m / z:[M+Na] + Calculated for C 32 H 27 79 BrN2NaO6S2701.0386; Found 701.0386.

[0093] Embodiment 27

[0094]

[0095] To a dry reaction tube, add biaryl diphenol derivative (1d) (31.2 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), then add 2 mL of dry DCM, then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:1) to obtain an off-white solid 3da (58.2 mg, 80%), mp: 90-92°C. f (EtOAc / PE=1:2)=0.3.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =16.642min(major),20.398min(minor),91%ee.[α] D 25 :-53.700(c=0.2,CH2Cl2). 1H NMR(400MHz, Acetone-d6)δ9.19(brs,1H),8.70(brs,1H),7.91(d,J=7.2Hz,1H),7 .76(brs,1H),7.69(d,J=8.0Hz,2H),7.62(d,J=8.0Hz,2H),7.43-7.37(m,3H),7.36 (d,J=8.4Hz,2H),7.31(d,J=8.0Hz,2H),7.19(s,1H),7.16(d,J=8.8Hz,2H),7.08-7 .02(m,1H),6.89(d,J=8.4Hz,1H),6.43(d,J=8.4Hz,1H),2.41(s,3H),2.35(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.6,154.0,144.8,144.6,140.8,139.7,139.3,138.0,137.9,137.3,132.7,131.4,13 0.6,130.4,130.0,129.9,129.0,128.8,128.0,121.5,121.3,121.0,107.9,103.0,21.6,21.5.HRMS(ESI)m / z:[M+K] + Calculated for C 32 H 27 IN2NaO6S2749.0247;Found 749.0247.

[0096] Embodiment 28

[0097]

[0098] To a dry reaction tube, add biaryl diphenol derivative (1e) (22.8 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3ea (58.5 mg, 91%), mp: 119-121°C. f (EtOAc / PE=1:2)=0.3.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R=11.602min(major),17.009min(minor),90%ee.[α] D 25 :-13.100(c=0.2,CH2Cl2). 1 H NMR(400MHz,Chloroform-d)δ8.03(d,J=8.0Hz,2H),7.95(d,J=7.6Hz,2H),7.86-7.78(m,2H),7.69-7.60(m,4H),7.59-7.53(m,4H),7.49(d,J=7.6Hz,1H ),7.35(d,J=8.4Hz,2H),7.18(d,J=8.7Hz,1H),6.81(d,J=8.8Hz,1H),4.97( brs,2H),3.09-2.95(m,1H),2.80(s,3H),2.73(s,3H),1.47(d,J=6.8Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ155.9,153.2,147.5,143.42,143.35,143.1,136.6,136.5,132.8,130.9,129.7,129.6,129.4,12 8.9,128.3,127.9,127.4,126.7,125.1,124.7,121.5,119.7,116.6,106.3,29.7,23.5,21.1,21.0.HRMS(ESI)m / z:[M+Na] + Calculated for C 35 H 34 N2NaO6S2665.1750; Found665.1751.

[0099] Embodiment 29

[0100]

[0101] Add biaryl diphenol derivative (1f) (26.2 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%) to a dry reaction tube. Then add 2 mL of dry DCM and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3fa (62.2 mg, 92%), mp: 213-215°C. f(EtOAc / PE = 1:2) = 0.3. HPLC(IB, i-PrOH / n-hexane = 50 / 50, flow rate = 1 mL / min, λ = 215 nm) t R = 10.149 min (minor), 11.923 min (major), 91% ee. [α] D 25 : -38.080 (c = 0.2, CH2Cl2). 1 H NMR(400 MHz, Acetone-d6) δ 9.07 (s, 1H), 8.13 (brs, 1H), 7.71 (d, J = 8.2 Hz, 2H), 7.67 - 7.45 (m, 3H), 7.44 - 7.37 (m, 3H), 7.37 - 7.30 (m, 5H), 7.29 - 6.86 (m, 9H), 6.62 (s, 1H), 6.22 (s, 1H), 2.39 (s, 3H), 2.34 (s, 3H). 13 C NMR(101 MHz, Acetone-d6) δ 156.7, 154.3, 144.8, 144.6, 143.8, 143.2, 142.6, 139.5, 138.1, 138.0, 133.1, 132.8, 131.7, 130.8, 130.7, 130.6, 130.3, 129.7, 129.1, 128.9 128.3, 128.1, 127.4, 121.5, 120.7, 118.5, 118.4, 107.8, 21.6, 21.2. HRMS(ESI) m / z: [M+Na] + Calculated for C 38 H 32 N2NaO6S2 699.1594; Found 699.1589.

[0102] Example 30

[0103]

[0104] To a dry reaction tube, add biaryl diphenol derivative (1g) (27.6mg, 0.1mmol, 1.0equiv), sulfonamide derivative (2a) (45.6mg, 0.11mmol, 1.1equiv), CPA1 (1.9mg, 0.0025mmol, 2.5mol%), and then add 2mL dry DCM, and stir at 0°C for 72h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain off-white solid 3ga (50.7mg, 73%), mp: 156-158°C. f (EtOAc / PE=1:2)=0.3.HPLC (IE, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =11.785min(major),17.533min(minor),96%ee.[α] D 25 :-47.000(c=0.2,CH2Cl2). 1 H NMR(400MHz, Acetone-d6)δ9.05(s,1H),8.04(brs,1H),7.69(d,J=6.8Hz,2H),7.65-7.42(m,3H),7.41-7.32(m,4H),7.31(dd,J =8.4,2.4Hz,4H),7.24(s,1H),7.21-7.05(m,5H),6.96(s,2H),6.64(s,1H),6.23(s,1H),2.39(s,3H),2.33(s,3H),2.25(s,3H). 13 CNMR(101MHz,Acetone-d6)δ156.6,154.3,144.8,144.6,143.8,139.7,139.6,138.1,137.9,136.8,132.9,132.8,130.9,130.7,130.6, 130.3,129.6,129.12,129.06,128.9,128.0,127.9,121.6,120.8,118.7,118.6,107.9,107.8,21.6,21.5,21.4.HRMS(ESI)m / z:[M+Na] + Calculated for C 39 H 34 N2NaO6S2713.1750; Found713.1753.

[0105] Embodiment 31

[0106]

[0107] To a dry reaction tube, add biaryl diphenol derivative (1h) (23.6 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3ha (60.0 mg, 92%), mp: 93-95°C. f (EtOAc / PE=1:2)=0.3.HPLC(IB, i-PrOH / n-hexane=70 / 30, flow rate=1mL / min, λ=215nm)t R =18.434min(major),22.926min(minor),90%ee.[α] D 25 :-88.700(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ9.21(brs,1H),8.42(brs,1H),7.91(d,J=8.0Hz,1H),7.87(d,J=8.4Hz,1H),7.77-7.56(m,5H),7.54-7.38( m,6H),7.34(d,J=8.0Hz,3H),7.30(d,J=8.0Hz,2H),7.22-7.16(m,2H),7.14-7.05(m,1H),6.61-6.53(m,1H),2.38(s,3H),2.32(s,3H). 13 C NMR (101MHz, Acetone-d6) δ157.4,154.8,144.71,144.69,139.1,138.1,138.0,137.5,134.9,133.7,132.3,131.4,130.6,130.4,130.0 ,129.3,129.13,129.08,129.0,128.1,126.81,126.75,126.65,126.61,121.4,121.1,116.3,108.0,21.7,21.6.HRMS(ESI)m / z:[M+Na] + Calculated for C36 H 30 N2NaO6S2673.1437; Found 673.1436.

[0108] Embodiment 32

[0109]

[0110] To a dry reaction tube, add biaryl diphenol derivative (1i) (31.5 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:1) to obtain an off-white solid 3ia (60.5 mg, 83%), mp: 86-88°C. f (EtOAc / PE=1:2)=0.2.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =11.207min(major),18.808min(minor),97%ee.[α] D 25 :-35.200(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ9.05 (s, 1H), 8.36 (s, 1H), 8.08 (d, J = 8.4Hz, 1H), 7.72(d,J=7.6Hz,1H),7.63(s,1H),7.57-7.53(m,2H),7.51-7.45(m,3H),7.3 6(s,2H),7.28-7.24(m,2H),7.21-7.14(m,4H),7.11(d,J=6.0Hz,1H),7.05-7 .01(m,2H),6.99-6.93(m,1H),6.43-6.38(m,1H)),2.24(s,3H),2.18(s,3H). 13C NMR (101MHz, Acetone-d6) δ157.2,154.7,144.7,144.6,139.1,138.2,138.1,137.5,135.0,133.0,132.9,132.8,131.9,130.9,130.6 1,130.55,130.3,129.2,129.1,128.3,128.1,127.8,127.5,123.1,121.34,121.27,115.4,108.1,21.6,21.5.HRMS(ESI)m / z:[M+Na] + Calculated for C 36 H 29 BrN2NaO6S2751.0543; Found 751.0540.

[0111] Embodiment 33

[0112]

[0113] To a dry reaction tube, add biaryl diphenol derivative (1j) (21.4 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3ja (57.0 mg, 91%), mp: 108-110°C. f (EtOAc / PE=1:2=0.4.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =11.823min(major),16.632min(minor),97%ee.[α] D 25 :-10.200(c=0.2,CH2Cl2). 1H NMR (400MHz, Acetone-d6) δ9.20 (s, 1H), 8.22 (s, 1H), 7.72 (d, J = 8.0Hz, 2H) ,7.65-7.61(m,2H),7.42(s,2H),7.40(s,1H),7.37(s,1H),7.35(d,J=3.6H z,2H),7.33(s,1H),7.20(d,J=8.8Hz,2H),7.08(s,1H),7.04-6.93(m,3H), 6.48(d,J=8.8Hz,1H),2.43(s,3H),2.37(s,3H),2.32(s,3H),2.03(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.6,154.1,144.7,144.6,139.2,138.7,138.1,138.0,137.4,132.0,131.6,130.8,130.6,13 0.5,130.3,129.10,129.05,128.0,127.3,121.4,121.1,117.7,114.3,107.9,21.6,21.5,21.3,19.9.HRMS(ESI)m / z:[M+K] + Calculated for C 34 H 32 KN2O6S2667.1333; Found667.1334

[0114] Embodiment 34

[0115]

[0116] To a dry reaction tube, add biaryl diphenol derivative (1k) (21.4 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3ka (58.5 mg, 93%), mp: 92-94°C. f (EtOAc / PE=1:2)=0.4.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R=10.560min(major),14.923min(minor),97%ee.[α] D 25 :-9.400(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ7.56-7.50(m,2H),7.47-7.42(m,2H),7.25-7.21(m,2H),7.18-7.12(m,4H),7.04-6.99(m,2H),6.97-6.94(m,1H) ),6.87-6.83(m,1H),6.80(dd,J=8.4,4.0Hz,1H),6.70(s,1H),6.306.34-6.26(m,1H),2.23(s,3H),2.17(s,3H),2.09(s,3H),1.84(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.5,154.0,144.7,144.6,139.2,138.1,138.0,137.4,135.7,135.6,133.6,132.5,130.8,1 30.7,130.5,130.3,129.4,129.1,128.0,125.9,121.3,121.0,117.9,107.9,21.6,21.5,21.1,19.5.HRMS(ESI)m / z:[M+K] + Calculated for C 34 H 32 KN2O6S2667.1333; Found 667.1334

[0117] Embodiment 35

[0118]

[0119] To a dry reaction tube, add biaryl diphenol derivative (11) (25.4 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:1) to obtain an off-white solid 31a (56.1 mg, 84%), mp: 97-89°C. f(EtOAc / PE = 1:2) = 0.4. HPLC(IA, i-PrOH / n-hexane = 50 / 50, flow rate = 1 mL / min, λ = 215 nm) t R = 13.355 min (major), 18.730 min (minor), 90% ee. [α] D 25 : -23.400 (c = 0.2, CH2Cl2). 1 1H NMR (400 MHz, Acetone-d6) δ 7.73 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 2.0 Hz, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.39 (s, 2H), 7.37 (s, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 6.8 Hz, 1H), 7.20 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.4 Hz, 1H), 6.49 (d, J = 8.8 Hz, 1H), 2.44 (s, 3H), 2.37 (s, 3H). 13 13C NMR (101 MHz, Acetone-d6) δ 156.8, 154.3, 144.9, 144.7, 139.0, 138.0, 137.8, 137.6, 136.8, 135.1, 134.3, 133.3, 131.6, 130.6, 130.4, 129.7, 129.1, 128.0, 127.8, 121.4, 121.3, 121.0, 115.0, 107.8, 21.6, 21.5. HRMS(ESI) m / z: [M+Na] + Calculated for C 32 H 26 Cl2N2NaO6S2 691.0502; Found 691.0502.

[0120] Example 36

[0121]

[0122] To a dry reaction tube, add biaryl diphenol derivative (1m) (25.4 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:1) to obtain an off-white solid 3ma (59.8 mg, 90%), mp: 74-76°C. f (EtOAc / PE=1:2)=0.4.HPLC(AD-H, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =14.928min(major),21.472min(minor),92%ee.[α] D 25 :-9.900(c=0.2,CH2Cl2). 1 HNMR(400MHz,Acetone-d6)δ9.11(s,1H),8.69(s,1H),7.98(s,1H),7.70(d,J =8.4Hz,2H),7.58(d,J=8.4Hz,2H),7.48(d,J=8.8Hz,1H),7.42-7.38(m,2H), 7.37-7.33(m,3H),7.31(d,J=8.0Hz,2H),7.26(d,J=2.4Hz,1H),7.20-7.15(m ,2H),6.93(d,J=8.8Hz,1H),6.46(d,J=8.8Hz,1H),2.42(s,3H),2.34(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.7,154.3,144.9,144.7,139.0,138.0,137.7,137.6,136.2,134.6,133.5,132.6,131 .8,131.6,130.6,130.4,129.8,129.2,129.1,128.0,121.3,121.2,115.1,108.0,21.6,21.5.HRMS(ESI)m / z:[M+Na] + Calculated for C 32 H 26 C l2N2NaO6S2691.0502; Found 691.0503.

[0123] Embodiment 37

[0124]

[0125] To a dry reaction tube, add biaryl diphenol derivative (1n) (21.4 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2a) (45.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3na (58.3 mg, 93%), mp: 179-181°C. HPLC (AD-H, i-PrOH / n-hexane=50 / 50, flow rate=1 mL / min, λ=215 nm) t R =16.928min(major),22.472min(minor),30%ee. R f (EtOAc / PE=1:2)=0.4. 1 H NMR (400MHz, Acetone-d6) δ9.22(s,1H),8.23(s,1H),7.73(d,J=8.4Hz,2H),7.63(d ,J=8.4Hz,2H),7.42(s,1H),7.40(s,2H),7.38(s,1H),7.35(d,J=4.4Hz,2H),7.33(s ,1H),7.20(d,J=8.8Hz,2H),7.14-7.07(m,2H),6.98(d,J=8.4Hz,1H),6.94(d,J=7. 6Hz, 1H), 6.49 (d, J = 8.4Hz, 1H), 2.44 (s, 3H), 2.37 (s, 3H), 2.30 (s, 3H), 1.97 (s, 3H). 13C NMR (101MHz, Acetone-d6) δ156.6,154.1,144.7,144.6,139.2,138.1,138.0,137.5,137.43,137.37,137.30,133.7,130.7, 130.5,130.3,130.1,129.8,129.1,128.0,126.3,121.3,121.0,118.3,107.9,21.6,21.5,20.8,16.6.HRMS(ESI)m / z:[M+Na] + Calculated for C 34 H 32 N2NaO6S2651.1594; Found651.1586.

[0126] Embodiment 38

[0127]

[0128] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2b) (42.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3ab (50.0 mg, 85%), mp: 101-103°C. f (EtOAc / PE=1:2)=0.4.HPLC (IE, i-PrOH / n-hexane=60 / 40, flow rate=1mL / min, λ=215nm)t R =16.507min(major),18.954min(minor),93%ee.[α] D 25 :-26.900(c=0.2,CH2Cl2). 1H NMR(400MHz,Chloroform-d)δ7.78(d,J=7.2Hz,2H),7.71(d,J=7.6Hz,2H),7.61(t,J=7. 2Hz,1H),7.53(t,J=7.6Hz,1H),7.47(t,J=8.0Hz,2H),7.42(t,J=7.6Hz,2H),7.38-7.33( m,2H),7.33-7.27(m,2H),7.21(d,J=8.8Hz,2H),7.17(d,J=7.2Hz,1H),6.99(d,J=8.8Hz, 2H),6.78(d,J=8.8Hz,1H),6.44(d,J=8.8Hz,1H),6.10(s,1H),4.95(s,1H),2.08(s,3H). 13 C NMR(101MHz,DMSO-d6)δ155.6,153.1,140.0,139.9,138.3,137.9,136.4,133.0,132.9,131.1,129.9,129.8,12 9.1,128.8,128.2,128.1,127.7,127.0,125.6,120.7,120.0,116.9,107.0,106.9,19.1.HRMS(ESI)m / z:[M+Na] + Calculated for C 31 H 26 N2NaO6S2609.1124; Found 609.1122.

[0129] Embodiment 39

[0130]

[0131] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2c) (46.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3ac (54.9 mg, 88%), mp: 90-92°C. f (EtOAc / PE=1:2)=0.4.HPLC(ID, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)tR =10.662min(minor),12.614min(major),94%ee.[α] D 25 :-29.500(c=0.2,CH2Cl2). 1 H NMR(400MHz,Acetone-d6)δ9.23(brs,1H),8.28(brs,1H),7.91-7.85(m,2H),7.82-7.76(m,2H),7.47-7.39(m,3H),7.34-7.27(m,4H),7.27-7.20(m,2H),7.19-7.15(m,3H),7.07(s,1H),7.04(d,J=8.8Hz,1H),6.49(d,J=8.4Hz,1H),2.05(s,3H). 13 C NMR(101MHz,Acetone-d6)δ166.1(d, 1 J C-F =253.5Hz),165.9(d, 1 J C-F =253.5Hz),156.7,153.9,139.4,138.9,137.3(d, 4 J C-F =3.0Hz),137.2,137.0(d, 4 J C-F =3.0Hz),133.7,132.0(d, 3 J C-F =9.1Hz),131.2,131.0(d, 3 J C-F =10.1Hz),130.8,129.22,129.15,128.8,126.6,121.9,120.8,117.9,117.1(d, 2 J C-F =23.2Hz),116.8(d, 2 J C-F =23.2Hz),108.1,20.0. 19 F NMR(282MHz,Acetone-d6)δ-107.1,-107.2.HRMS(ESI)m / z:[M+Na] + Calculated forC 31 H 24 F2N2NaO6S2645.0936;Found 645.0936.

[0132] Embodiment 40

[0133]

[0134] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2d) (50.2 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3ad (57.0 mg, 87%), mp: 109-111°C. f (EtOAc / PE=1:2)=0.2.HPLC(IA, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=215nm)t R =14.184min(major),16.228min(minor),94%ee.[α] D 25 :-29.300(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ8.35(brs,1H),7.80(d,J=8.4Hz,2H),7.72(d,J=8.4Hz,2H),7.56(dd,J=8.8,2.8Hz,4H),7.41(d,J=8.4H z,2H),7.24(d,J=7.6Hz,1H),7.20(d,J=8.4Hz,2H),7.17(d,J=8.8Hz,2H),7.06(d,J=8.8Hz,2H),6.50(d,J=8.8Hz,1H),2.06(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.7,153.8,139.9,139.5,139.4,138.9,137.1,133.7,132.1,131.2,130.8,130.79,1 30.2,130.0,129.9,129.8,129.2,128.82,128.78,126.6,122.0,120.7,117.9,108.1,19.9.HRMS(ESI)m / z:[M+Na] + Calculated for C 31 H 24 C l2N2NaO6S2677.0345; Found 677.0344.

[0135] Embodiment 41

[0136]

[0137] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2e) (52.4 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:1) to obtain a yellow solid 3ae (55.0 mg, 81%), mp: 127-129°C. f (EtOAc / PE=1:2)=0.2.HPLC (IE, i-PrOH / n-hexane=75 / 35, flow rate=0.7mL / min, λ=254nm)t R =20.849min(major),23.734min(minor),94%ee.[α] D 25 :-18.200(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ9.45(brs,1H), δ8.32(s,1H),8.26-8.22(m,4H),7.96-7.92(m,2H),7.86-7.82(m,2H),7.31(d,J=8.8H z,2H),7.27(s,1H),7.12-7.07(m,3H),7.07-7.02(m,2H),7.00(d,J=8.8Hz,1H),6.90(s,1H),6.38(d,J=8.8Hz,1H),1.91(s,3H). 13 C NMR (75MHz, Acetone-d6) δ156.0,152.8,150.4,150.2,145.9,145.4,138.5,138.1,136.1,132.4,131.2,130.8,13 0.0,129.4,128.62,128.58,128.0,125.8,124.4,124.0,121.4,119.5,117.0,107.3,19.0.HRMS(ESI)m / z:[M+Na] +Calculated for C 31 H 24 N4NaO 10 S2699.0826; Found 699.0809.

[0138] Embodiment 42

[0139]

[0140] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2f) (53.6 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3af (60.0 mg, 87%), mp: 132-134°C. f (EtOAc / PE=1:2)=0.3.HPLC (IE, i-PrOH / n-hexane=55 / 45, flow rate=1mL / min, λ=215nm)t R =17.081min(major),19.791min(minor),95%ee.[α] D 25 :-40.000(c=0.2,CH2Cl2). 1 H NMR(400MHz, Acetonitrile-d3)δ8.69(d,J=8.8Hz,1H),8.49(brs,1H),8.27(d,J=7.2Hz,1H),8.24(s,1H ),8.19(d,J=8.4Hz,2H),8.06(d,J=7.6Hz,2H),8.02(d,J=8.4Hz,1H),7.79-7.73(m,1H),7.68(t,J=7.6H z,1H),7.61-7.51(m,3H),7.29(d,J=3.6Hz,2H),7.28-7.21(m,2H),7.19(d,J=8.0Hz,2H),6.98(d,J=8.8 Hz,2H),6.94(s,1H),6.81(s,1H),6.75(d,J=8.8Hz,1H),6.29(s,1H),6.27(d,J=8.8Hz,1H),1.89(s,3H). 13CNMR(101MHz,Acetone-d6)δ156.6,153.9,138.8,138.6,137.6,136.51,136.4 9,135.7,135.5,135.49,135.3,135.2,133.8,132.0,131.8,131.2,130.7,130. 1,130.0,129.9,129.7,129.1,129.0,128.6,128.4,127.9,127.6,126.6,126.5 ,125.4,125.3,125.2,120.6,120.5,117.8,107.8,19.9.HRMS(ESI)m / z:[M+Na] + Calculated for C 39 H 30 N2NaO6S2709.1437; Found 709.1438.

[0141] Embodiment 43

[0142]

[0143] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2g) (51.9 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 36 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3ag (50.4 mg, 75%), mp: 103-105°C. f (EtOAc / PE=1:2)=0.5.HPLC(IA, i-PrOH / n-hexane=60 / 40, flow rate=1mL / min, λ=215nm)t R =11.890min(major),14.600min(minor),94%ee.[α] D 25 :-26.700(c=0.2,CH2Cl2). 1H NMR (400MHz, Acetone-d6) δ9.13(brs,1H),8.32(brs,1H),7.41(d,J=8.4Hz,2H),7.26-7.19(m,2H),7.18-7.10(m,2H),7.08(d,J=9.2Hz,2H),7.0 5(s,1H),6.99(s,2H),6.96(d,J=7.6Hz,1H),6.94(s,2H),6.43(d,J=8.4 Hz,1H),2.61(s,6H),2.31(s,6H),2.27(s,3H),2.24(s,3H),1.95(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.7,154.0,143.6,143.4,141.5,140.1,139.0,138.8,137.4,135.1,134.6,133.8,132.9,132. 6,132.0,131.9,130.7,129.6,128.6,126.5,120.7,120.1,117.8,107.9,23.5,23.2,21.0,20.9,19.8.HRMS(ESI)m / z:[M+Na] + Calculated for C 37 H 38 N2NaO6S2693.2063; Found 693.2062.

[0144] Embodiment 44

[0145]

[0146] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2h) (49.1 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain an off-white solid 3ah (55.0 mg, 85%), mp: 178-180°C. f (EtOAc / PE=1:2)=0.4.HPLC (IE, i-PrOH / n-hexane=50 / 50, flow rate=1mL / min, λ=254nm)t R=18.569min(major),21.197min(minor),92%ee.[α] D 25 :-23.700(c=0.2,CH2Cl2). 1 H NMR (400MHz, DMSO-d6) δ10.26(s,1H),9.36(s,1H),8.24(s,1H),7.71(d,J= 8.4Hz,2H),7.55(d,J=8.4Hz,2H),7.30(s,2H),7.18(d,J=7.6Hz,2H),7.14( d,J=11.2Hz,1H),7.06(d,J=8.4Hz,4H),7.01(d,J=8.4Hz,2H),6.95(s,1H) ,6.80(s,1H),6.34(d,J=8.8Hz,1H),3.84(s,3H),3.79(s,3H),1.91(s,3H). 13 C NMR (101MHz, Acetone-d6) δ164.2,164.0,156.5,154.0,139.2,138.8,137.5,134.0,132.4,132.3,132.0,131.3,130.8 ,130.7,130.2,129.0,128.6,126.5,121.4,121.2,117.8,115.1,114.9,108.0,56.2,56.2,20.0.HRMS(ESI)m / z:[M+Na] + Calculated for C 33 H 30 N2NaO8S2669.1336; Found669.1336.

[0147] Embodiment 45

[0148]

[0149] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2i) (43.8 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 24 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3ai (53.8 mg, 90%), mp: 94-96°C. f(EtOAc / PE = 1:2) = 0.2. HPLC(IA, i-PrOH / n-hexane = 50 / 50, flow rate = 1 mL / min, λ = 215 nm) t R = 12.085 min (major), 15.353 min (minor), 96% ee. [α] D 25 : -37.700 (c = 0.2, CH2Cl2). 1 1H NMR (400 MHz, Acetone-d6) δ 8.27 (brs, 1H), 7.91 (dd, J = 5.2, 1.8 Hz, 1H), 7.80 (dd, J = 5.2, 1.6 Hz, 1H), 7.65 - 7.54 (m, 3H), 7.49 (d, J = 8.8 Hz, 2H), 7.27 - 7.21 (m, 4H), 7.21 - 7.18 (m, 2H), 7.16 (s, 1H), 7.10 (dd, J = 4.8, 4.0 Hz, 2H), 7.04 (d, J = 8.8 Hz, 1H), 6.51 (d, J = 8.8 Hz, 1H), 2.08 (s, 3H). 13 13C NMR (101 MHz, Acetone-d6) δ 156.7, 154.1, 141.3, 141.2, 139.4, 138.9, 137.1, 134.4, 134.2, 133.9, 133.8, 133.5, 132.1, 130.8, 130.6, 129.0, 128.7, 128.40, 128.37, 126.6, 122.0, 120.9, 117.9, 108.0, 20.0. HRMS(ESI) m / z: [M+Na] + Calculated for C 27 H 22 N2NaO6S4621.0253; Found 621.0253.

[0150] Example 46

[0151]

[0152] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2j) (45.5 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 36 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3aj (56.0 mg, 91%), mp: 75-77°C. f (EtOAc / PE=1:2)=0.3.HPLC (IE, i-PrOH / n-hexane=60 / 40, flow rate=1mL / min, λ=215nm)t R =13.343min(major),15.143min(minor),98%ee.[α] D 25 :-11.200(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ8.52(brs,1H),7.63(brs,1H),7.51(d,J=8.8Hz,2H),7.45(d,J=4.4Hz,1H),7.43(d,J=2.0Hz,1H),7.37-7.31(m,4H),7.31 (s,5H),7.29-7.26(m,3H),7.24(q,J=2.4Hz,2H),7.23-7.21(m,1H),7.20- 7.18(m,1H),6.59(d,J=8.4Hz,1H),4.73(s,2H),4.43(s,2H),2.16(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.6,153.6,139.3,139.1,137.5,133.7,132.3,132.2,132.1,132.0,131.0,130.50,130.48 ,129.4,129.3,129.25,128.9,128.2,126.8,121.6,120.8,118.0,108.5,101.4,58.9,58.2,20.1.HRMS(ESI)m / z:[M+Na] + Calculated for C 33 H 30 N2NaO6S2637.1437; Found 637.1435.

[0153] Embodiment 47

[0154]

[0155] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2k) (28.8 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 4 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:1) to obtain an off-white solid 3ak (43.9 mg, 95%), mp: 255-257°C. f (EtOAc / PE=1:2)=0.1.HPLC(IA, i-PrOH / n-hexane=60 / 40, flow rate=1mL / min, λ=215nm)t R =6.312min(major),8.907min(minor),98%ee.[α] D 25 :-28.400(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ8.63(brs,1H),8.20(brs,1H),7.59(s,1H),7.56(d,J=8.8Hz,2H),7.34(d,J=8.8Hz,1H),7.32-7.29 (m,2H),7.29-7.23(m,2H),7.23-7.20(m,1H),7.19-7.15(m,1H),6.58(d,J=8.8Hz,1H),3.20(s,3H),2.99(s,3H),2.13(s,3H). 13 C NMR (101MHz, Acetone-d6) δ156.6,153.7,139.8,139.0,137.5,133.6,132.2,131.8,130.9 ,128.9,128.2,126.8,121.6,121.5,118.0,108.5,40.1,39.6,20.1.HRMS(ESI)m / z:[M+Na] + Calculated for C 21 H 22 N2NaO6S2485.0811; Found 485.0812.

[0156] Embodiment 48

[0157]

[0158] To a dry reaction tube, add biaryl diphenol derivative (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonamide derivative (2l) (31.9 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%), and then add 2 mL of dry DCM, and stir at 0°C for 4 h under argon. The reaction solution was evaporated to dryness under reduced pressure, and the residue was purified by column chromatography (silica gel, eluent: EtOAc / PE = 1:4-1:2) to obtain an off-white solid 3aI (45.7 mg, 93%), mp: 179-181°C. f (EtOAc / PE=1:2)=0.1.HPLC(IA, i-PrOH / n-hexane=60 / 40, flow rate=1mL / min, λ=215nm)t R =7.301min(major),9.615min(minor),98%ee.[α] D 25 :-27.600(c=0.2,CH2Cl2). 1 H NMR (400MHz, Acetone-d6) δ8.67(brs,1H),8.42(brs,1H),7.54(d,J=8.8Hz,2H) ,7.35(d,J=8.8Hz,1H),7.33(s,1H),7.30(d,J=8.8Hz,2H),7.27(s,1H),7.23(dd ,J=7.2,1.6Hz,1H),7.21-7.11(m,2H),6.58(d,J=8.8Hz,1H),3.40(q,J=7.2Hz,2 H),3.15-3.10(m,2H),2.11(s,3H),1.36(t,J=7.2Hz,3H),1.27(t,J=7.2Hz,3H). 13 C NMR (101MHz, Acetone-d6) δ156.6,153.6,139.6,139.0,137.5,133.7,132.2,132.0,130.9,128. 8,128.5,126.7,121.4,121.1,117.9,108.4,47.6,46.3,20.0,8.52,8.4.HRMS(ESI)m / z:[M+Na] + Calculated for C 23 H26 N2NaO6S2513.1124; Found513.1123.

[0159] Embodiment 49

[0160]

[0161] Add biarylphenol compound (1a) (20.0 mg, 0.1 mmol, 1.0 equiv), sulfonylamino compound (2m) (31.9 mg, 0.11 mmol, 1.1 equiv), CPA1 (1.9 mg, 0.0025 mmol, 2.5 mol%) to a dry reaction tube. Then add 2 mL of dry DCM and stir at 0°C for 24 h under argon. The reaction solution is evaporated to dryness under reduced pressure, and the residue is purified by column chromatography (silica gel, eluent: EtOAc / PE=1:4-1:2) to obtain product 3am (yield <5%).

[0162] The present invention will be further described below by specific examples, but the present invention is not limited to the following examples. Unless otherwise defined, the technical terms used in the following examples have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. The test reagents used in the following examples, unless otherwise specified, are all conventional reagents, which can be purchased on the market or synthesized according to conventional methods in the art; the experimental methods, unless otherwise specified, are all conventional methods.

Claims

1. A method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity, characterized in that: Adding a biaryl diphenol derivative, a sulfonamide derivative, and a chiral phosphoric acid catalyst into a reaction container, and then adding a solvent, stirring and reacting under argon protection, and purifying after the reaction to obtain an optically pure axial chiral sulfonamide biaryl diphenol derivative; Ar is any of the following substituents: R is any of the following substituents:

2. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: The biaryl diphenol derivative is one of the following structural formulas:

3. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: The sulfonamide derivative is one of the following structural formulas:

4. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: The chiral phosphoric acid catalyst is one of the following:

5. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: The molar ratio of the biaryl diphenol derivative, the sulfonamide derivative and the chiral phosphoric acid is: 2-1:2-1.1:0.05-0.

01.

6. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: The solvent is one of dichloromethane, dichloroethane, toluene, chloroform, ethylene glycol dimethyl ether, tetrahydrofuran, acetonitrile and ether.

7. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: When the biaryl diphenol derivative is 1 equivalent, the concentration of the reaction solution is: 0.025-0.10 mol / L.

8. The method for synthesizing axially chiral sulfonamide biaryl diphenol derivatives with high stereoselectivity according to claim 1, characterized in that: The reaction temperature is -20-25°C, and the reaction time is 4-72h.

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