Chiral indolo eight-membered lactone compound, synthetic method thereof and spiro-oxoindole compound

Abstract

The invention belongs to the field of organic chemistry, and relates to a chiral indolo eight-membered lactone compound, a synthesis method thereof and a spirooxoindole compound. The chiral indolo eight-membered lactone compound is a compound with a structure shown as a formula (I), in the # imgabs0 # formula (I), R1 is selected from at least one of hydrogen, C1-C4 alkyl groups, C1-C4 alkoxy groups, halogen substituted C1-C4 alkyl groups, C2-C4 carboxylic ester groups, pinacol boric acid ester groups and halogen; r2 is hydrogen, a tert-butyl carbonate group, a C1-C4 alkyl group or a phenyl group; r3 is alkyl or benzyloxy propyl of C1-C4; r4 is at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C2-C4 carboxylic ester group, nitryl and halogen or naphthyl formed by the R4 and substituted phenyl together. According to the invention, a series of chiral indolo eight-membered lactone derivatives are synthesized, and different chiral spiro-oxoindole derivatives are selectively synthesized through a one-step rearrangement reaction.

Description

Technical Field

[0001] The invention belongs to the field of organic chemistry, and in particular relates to a chiral indole octa-membered lactone compound and a synthesis method thereof, and a spiro-oxidized indole compound. Background Art

[0002] Indole-containing oxygen heterocycles and spiro-oxidized indole structures are important core skeletons of many biologically active natural products and drug molecules, and have shown strong anti-tumor, anti-viral and other pharmacological activities in the medical field. Therefore, the efficient synthesis of indole-containing oxygen heterocycles and spiro-oxidized indole derivatives has attracted widespread attention from medicinal chemists and organic synthetic chemists. Although chemists have developed many effective methods to synthesize these two types of advantageous skeletons respectively in the past few decades, there is still a lack of a general scheme for the synthesis of these two types of skeletons, and a lack of efficient chiral synthesis strategies.

[0003] Therefore, developing new catalytic synthesis strategies to achieve the efficient construction of chiral indole-containing oxygen-containing heterocycles and spiro-oxidized indole skeletons has important practical significance and application potential. Summary of the invention

[0004] In order to solve the above-mentioned problems existing in the prior art, the present invention plans to develop a novel asymmetric metal-catalyzed dipolar cyclization reaction and establish a mild and efficient synthesis scheme for indole octa-membered lactone and spiro-oxidized indole, hoping to start from simple and readily available raw materials and highly selectively synthesize a series of chiral indole octa-membered lactone derivatives with diverse structures, and then selectively synthesize different chiral spiro-oxidized indole derivatives through a simple one-step rearrangement reaction of such compounds, thereby laying a material foundation for the screening of the biological activities of these heterocyclic compounds, and also providing a new method for the development of the total synthesis of natural products with indole polylactone or spiro-oxidized indole structures.

[0005] In order to achieve the above-mentioned object, the first aspect of the present invention provides a chiral indole 8-membered lactone compound, wherein the chiral indole 8-membered lactone compound is a compound having a structure shown in formula (I),

[0006]

[0007] In formula (I), R 1 At least one selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen-substituted C1-C4 alkyl, C2-C4 carboxylate, pinacol borate and halogen; R 2 is hydrogen, tert-butyl carbonate, C1-C4 alkyl or phenyl; R 3 is a C1-C4 alkyl group or a benzyloxypropyl group; R 4It is at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C2-C4 carboxylate, nitro and halogen, or together with the phenyl substituted therewith, forms a naphthyl group.

[0008] The second aspect of the present invention provides a method for synthesizing the chiral indole octa-membered lactone compound, comprising the following steps:

[0009] Under the protection of a first inert gas and in the presence of a first solvent, a compound having a structure represented by formula (IV), a compound having a structure represented by formula (V), a chiral ligand and a metal catalyst are mixed, and a dipolar cyclization reaction occurs under light conditions to obtain the compound having a structure represented by formula (I);

[0010]

[0011] R in formula (IV) 1 -R 2 With R in formula (I) 1 -R 2 The same as the definition; in formula (V), R 3 -R 4 With R in formula (I) 3 -R 4 The definition is the same.

[0012] The third aspect of the present invention provides a spiro-oxidized indole compound, wherein the spiro-oxidized indole compound is a product obtained by rearrangement of the chiral indole octa-membered lactone compound;

[0013] The spiro oxidized indole compound is a compound having a structure represented by formula (II) or a compound having a structure represented by formula (III);

[0014]

[0015] R in formula (II)-(III) 1 -R 4 With R in formula (I) 1 -R 4 The definition is the same.

[0016] The fourth aspect of the present invention provides a method for synthesizing the spirooxidindole compound, comprising the following steps:

[0017] The compound having the structure shown in formula (I) is rearranged under the action of a catalyst to obtain a compound having the structure shown in formula (II) or a compound having the structure shown in formula (III).

[0018] The present invention starts from simple and readily available raw materials and highly selectively synthesizes a series of chiral indole octa-membered lactone derivatives with diverse structures. Subsequently, the compounds are subjected to a simple one-step rearrangement reaction to selectively synthesize different chiral spiro-oxidized indole derivatives, thereby laying a material foundation for the screening of the biological activities of these heterocyclic compounds and also providing a new method for the total synthesis of natural products with indole poly-lactone or spiro-oxidized indole structures.

[0019] Other features and advantages of the present invention will be described in detail in the following detailed description. DETAILED DESCRIPTION

[0020] The preferred embodiments of the present invention will be described in more detail below. Although the preferred embodiments of the present invention are described below, it should be understood that the present invention can be implemented in various forms and should not be limited to the embodiments set forth herein.

[0021] In order to achieve the above-mentioned object, the first aspect of the present invention provides a chiral indole 8-membered lactone compound, wherein the chiral indole 8-membered lactone compound is a compound having a structure shown in formula (I),

[0022]

[0023] In formula (I), R 1 At least one selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen-substituted C1-C4 alkyl, C2-C4 carboxylate, pinacol borate and halogen; R 2 is tert-butyl carbonate, C1-C4 alkyl or phenyl; R 3 is a C1-C4 alkyl group or a benzyloxypropyl group; R 4 It is at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C2-C4 carboxylate, nitro, and halogen, or together with the phenyl substituted therewith, forms a naphthyl group.

[0024] According to the present invention, preferably, R 1 is hydrogen, 2-fluoro, 2-methoxy, 2-pinacol borate, 3-chloro, 3-fluoro, 3-trifluoromethyl, 3-carboxylic acid methyl ester, 3-methyl or 2,4-difluoro; R 2 is hydrogen, tert-butyl carbonate, methyl or phenyl; R 3 is methyl, isobutyl, 3-benzyloxypropyl; R 4 It is hydrogen, 7-fluoro, 7-chloro, 7-bromo, 7-carboxylic acid methyl ester, 7-nitro, 7-methyl, 8-methoxy, 8-fluoro, 8-chloro, 7,8-dichloro or together with the phenyl substituted therewith it forms a naphthyl group.

[0025] The second aspect of the present invention provides a method for synthesizing the chiral indole octa-membered lactone compound, comprising the following steps:

[0026] Under the protection of a first inert gas and in the presence of a first solvent, a compound having a structure represented by formula (IV), a compound having a structure represented by formula (V), a chiral ligand and a metal catalyst are mixed, and a dipolar cyclization reaction occurs under light conditions to obtain the compound having a structure represented by formula (I);

[0027]

[0028] R in formula (IV) 1 -R 2 With R in formula (I) 1 -R 2 The same as the definition; in formula (V), R 3 -R 4 With R in formula (I) 3 -R 4 The definition is the same.

[0029] According to the present invention, preferably, the metal catalyst and the chiral ligand are first dissolved in a first solvent, stirred for 20 to 40 minutes, and then mixed with the compound having the structure shown in formula (IV) and the compound having the structure shown in formula (V).

[0030] According to the present invention, preferably, the first inert gas is argon and / or nitrogen;

[0031] The first solvent is dichloromethane and / or 1,2-dichloroethane;

[0032] The metal catalyst is selected from at least one of tris(dibenzylideneacetone)dipalladium chloroform adduct, bis(dibenzylideneacetone)palladium and tetrakistriphenylphosphine palladium;

[0033] The chiral ligand is selected from at least one of the compounds L1, L2, and L3 having the structure shown in formula (VI);

[0034]

[0035] The molar ratio of the compound having the structure represented by formula (IV), the compound having the structure represented by formula (V), the chiral ligand and the metal catalyst is 20-40:40-60:1-2:1;

[0036] The illumination adopts visible light, the wavelength of the visible light is 350-456nm, and the light intensity is 3-15W;

[0037] The conditions of the dipolar cyclization reaction include: temperature of 0 to 40° C. and time of 2 to 10 hours.

[0038] The third aspect of the present invention provides a spiro-oxidized indole compound, wherein the spiro-oxidized indole compound is a product obtained by rearrangement of the chiral indole octa-membered lactone compound;

[0039] The spiro oxidized indole compound is a compound having a structure represented by formula (II) or a compound having a structure represented by formula (III);

[0040]

[0041] R in formula (II)-(III) 1 -R 4 With R in formula (I) 1 -R 4 The definition is the same.

[0042] According to the present invention, preferably, in formula (II), R 1 is hydrogen, 2-fluoro or 2-methoxy; R 2 is hydrogen, tert-butyl carbonate or methyl; R 3 is methyl or 3-benzyloxypropyl; R 4 is hydrogen or forms a naphthyl group together with the phenyl group substituted by it; in formula (III), R 1 is hydrogen, 2-methoxy or 3-chloro; R 2 is hydrogen, tert-butyl carbonate or phenyl; R 3 is methyl or 3-benzyloxypropyl; R 4 It is hydrogen or, together with the phenyl group it replaces, forms a naphthyl group.

[0043] The fourth aspect of the present invention provides a method for synthesizing the spirooxidindole compound, comprising the following steps:

[0044] The compound having the structure shown in formula (I) is rearranged under the action of a catalyst to obtain a compound having the structure shown in formula (II) or a compound having the structure shown in formula (III).

[0045] According to the present invention, preferably, the method for synthesizing the compound having the structure represented by formula (II) comprises the following steps:

[0046] Under the protection of a second inert gas and in the presence of a second solvent, reacting the compound having the structure represented by formula (I) with the first catalyst to obtain the compound having the structure represented by formula (II);

[0047] Preferably, the second inert gas is argon and / or nitrogen; the second solvent is selected from at least one of tetrahydrofuran, dichloromethane and acetonitrile; the first catalyst is selected from at least one of cesium carbonate, potassium phosphate and 4-dimethylaminopyridine; the molar ratio of the compound having the structure represented by formula (I) to the first catalyst is 1-10:1; the reaction conditions include: temperature of 0 to 40°C and time of 8 to 20 hours.

[0048] According to the present invention, preferably, the method for synthesizing the compound having the structure represented by formula (II) comprises the following steps:

[0049] Under a third inert gas protection condition and in the presence of a third solvent, reacting the compound having the structure represented by formula (I) with a second catalyst to obtain the compound having the structure represented by formula (II);

[0050] Preferably, the third inert gas is argon and / or nitrogen; the third solvent is selected from at least one of acetone, tetrahydrofuran and dichloromethane; the second catalyst is selected from at least one of dimethyldioxirane, meta-chloroperbenzoic acid and potassium peroxymonosulfonate; the molar ratio of the compound having the structure represented by formula (I) and the second catalyst is 1-0.5:1; the reaction conditions include: temperature of -10 to 10°C and time of 8 to 20 hours.

[0051] Example 1

[0052] Preparation of Compound I-1

[0053]

[0054] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-1 with a yield of 87% and an ee value (enantiomeric excess) of 88%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0055] 1H NMR (400MHz, CDCl3) δ (ppm) 7.81-7.72 (m, 1H), 7.36-7.28 (m, 1H), 7.18-7.13 (m, 2H), 7.14-7 .06(m,2H),6.93(d,J=5.1Hz,3H),5.25(s,1H),5.16(s,1H),3.47(d,J=15.1Hz,1H),3.29(d,

[0056] J=15.1Hz,1H),3.14(d,J=14.9Hz,1H),2.87(d,J=14.9Hz,1H),1.67(s,3H),1.65(s,9H).

[0057] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.9,148.2,141.9,140.4,139.5,132.1,127.6,126.4,126 .0,125.2,123.8,122.6,117.7,117.0,114.8,103.0,83.6,52.3,46.4,33.3,30.3,28.2.

[0058] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =95:5, flow rate 1.0mL / min, λ=220nm,

[0059] t1=7.58min,t2=9.50min.

[0060] High resolution: Calculated value: [M+Na] + :440.1832, measured value:440.1832.

[0061] Optical rotation: [α] D 25 =11.30 (c = 0.77 in CHCl3).

[0062] Example 2

[0063] Preparation of Compound I-2

[0064]

[0065] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-2 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-2 with a yield of 58% and an ee value (enantiomeric excess) of 93%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0066] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.84 (d, J=1.8Hz, 1H), 7.22 (d, J=

[0067] 8.3Hz,1H),7.13(dd,J=8.3,1.9Hz,1H),7.09(dd,J=7.5,2.1

[0068] Hz,2H),6.99-6.91(m,3H),5.23(s,1H),5.17(s,1H),3.43(d,J

[0069] =15.1Hz,1H),3.26(d,J=15.1Hz,1H),3.14(d,J=15.0Hz,1H),2.87(d,J=15.0Hz,1H),1.66(s,3H),1.66(s,9H).

[0070] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.6,147.9,141.7,140.3,139.8,132.4,129.5,127.7,126 .7,125.2,124.5,123.1,118.5,117.2,115.2,102.8,84.3,52.3,46.3,33.5,30.3,28.2.

[0071] Chiral HPLC: Chiral OZ column, V 正己烷 / V 异丙醇 =95:5, flow rate 1.0mL / min, λ=254nm,

[0072] t1=4.78min,t2=5.47min.

[0073] High resolution: Calculated value: [M+Na] + :474.1443, measured value:474.1444.

[0074] Optical rotation: [α] D 25 =182.00 (c = 0.99 in CHCl3).

[0075] Example 3

[0076] Preparation of Compound I-3

[0077]

[0078] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-3 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-3, with a yield of 55% and an ee value (enantiomeric excess): 87%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0079] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.52 (dd, J = 10.6, 2.4Hz, 1H), 7.22

[0080] (dd,J=8.6,5.4Hz,1H),7.10-7.06(m,2H),6.96-6.87(m,4H),5.24(s,1H),5.17(s,1H),3.43(d,J=15.1Hz,1H),3.26(d,J=

[0081] 15.0Hz,1H),3.13(d,J=15.1Hz,1H),2.86(d,J=15.0Hz,1H),1.66(s,3H),1.66(s,6H).

[0082] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.7, 160.4 (d, J = 238.9Hz), 148.0, 141.8, 140.3, 139.5, 132.3 (d, J = 12.9Hz), 127.7, 126.6, 12 5.2,122.2,118.4(d,J=9.6Hz),117.1,110.6(d,J=24.0Hz),102.8,102.5(d,J=29.3Hz),84.1,52.3,46.3,33.7,30.3,28.2.

[0083] 19 F NMR(376MHz, CDCl3)δ(ppm)-117.2.

[0084] Chiral HPLC: Chiral OZ column, V 正己烷 / V 异丙醇 =95:5, flow rate 1.0mL / min, λ=254nm,

[0085] t1=4.74min,t2=5.53min.

[0086] High resolution: Calculated value: [M+Na] + :458.1738, measured value:458.1737.

[0087] Optical rotation: [α] D 25 = -17.80 (c = 0.92 in CHCl3).

[0088] Example 4

[0089] Preparation of Compound I-4

[0090]

[0091] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-4 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯=100:1 column chromatography to obtain the target product of formula I-4 with a yield of 86% and an ee value (enantiomeric excess) of 89%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0092] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.13 (s, 1H), 7.41 (s, 2H), 7.10 (s, 2H), 6.94 (s, 3H), 5.26 (s, 1H), 5 .18(s,1H),3.48(d,J=15.3Hz,1H),3.31(d,J=15.4Hz,1H),3.15(d,J=15.1Hz,1H),2.88(d,J=

[0093] 14.7Hz,1H),1.67(s,12H).

[0094] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.4, 147.8, 141.6, 141.5, 140.3, 131.3, 128.7, 128.4 (q, J=26.5Hz), 127.8, 126.7, 125.7 (q, J=

[0095] 32.1Hz), 125.3, 124.7 (q, J = 271.8Hz), 119.4 (q, J = 3.7Hz), 118.0, 117.4, 112.5 (q, J = 4.5Hz), 102.8, 84.6, 52.4, 46.4, 33.1, 30.2, 28.2.

[0096] 19 F NMR(376MHz, CDCl3)δ(ppm)-61.0.

[0097] Chiral HPLC: Chiral OZ column, V 正己烷 / V 异丙醇 =97:3, flow rate 0.5mL / min, λ=254nm,

[0098] t1=10.14min,t2=11.61min.

[0099] High resolution: Calculated value: [M+Na] + :508.1706, measured value:508.1706.

[0100] Optical rotation: [α] D 25 =65.57 (c = 1.07 in CHCl3).

[0101] Example 5

[0102] Preparation of Compound I-5

[0103]

[0104] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-5 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-5 with a yield of 81% and an ee value (enantiomeric excess) of 92%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0105] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.50 (d, J=1.4Hz, 1H), 7.88 (dd, J=

[0106] 8.2,1.5Hz,1H),7.36(d,J=8.2Hz,1H),7.12(dd,J=6.6,3.0Hz,2H),6.98-6.90(m,3H),5.26 (s,1H),5.18(s,1H),3.91(s,3H),3.48(d,J=15.2Hz,1H),3.29(d,J=15.2Hz,1H),3.15(d,J=

[0107] 15.0Hz,1H),2.88(d,J=14.9Hz,1H),1.67(s,12H).

[0108] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.4, 167.6, 147.8, 141.9, 141.6, 140.3, 131.4, 130.0, 127.8, 126.8,125.3,124.0,117.4,117.3,116.7,103.0,84.4,52.4,52.0,46.4,33.2,30.2,28.2.

[0109] Chiral HPLC: Chiral IE columns, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=220nm,

[0110] t1=14.54min,t2=16.78min.

[0111] High resolution: Calculated value: [M+Na] + :498.1887, measured value:498.1886.

[0112] Optical rotation: [α] D 25 =-27.07 (c = 1.47 in CHCl3).

[0113] Example 6

[0114] Preparation of Compound I-6

[0115]

[0116] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-6 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-6 with a yield of 99% and an ee value (enantiomeric excess) of 87%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0117] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.65 (s, 1H), 7.19 (d, J = 7.9Hz, 1H), 7.11 (dd, J = 6.2, 3.1Hz, 2H), 6.98 (d, J = 8.8Hz, 1H), 6.97-6.93

[0118] (m,3H),5.23(s,1H),5.14(s,1H),3.42(d,J=15.1Hz,1H),3.27

[0119] (d,J=15.2Hz,1H),3.13(d,J=14.8Hz,1H),2.85(d,J=14.8

[0120] Hz,1H),2.39(s,3H),1.66(s,3H),1.65(s,9H).

[0121] 13 C NMR (100MHz, CDCl3) δ (ppm) 174.0,148.5,142.1,140.6,139.0,133.8,132.5,127.7,126.5, 125.3,123.9,123.7,117.4,117.0,115.1,103.0,83.5,52.4,46.5,33.1,30.5,28.2,22.0.

[0122] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0123] t1=6.80min,t2=8.92min.

[0124] High resolution: Calculated value: [M+Na] + :454.1989, measured value:454.1988.

[0125] Optical rotation: [α] D 25 =96.90 (c = 1.02 in CHCl3).

[0126] Example 7

[0127] Preparation of Compound I-7

[0128]

[0129] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-7 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-7 with a yield of 70% and an ee value (enantiomeric excess) of 90%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0130] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.73 (dd, J = 9.3, 4.7Hz, 1H), 7.16-

[0131] 7.04(m,2H),6.97(d,J=10.6Hz,1H),6.95-6.92(m,3H),6.85

[0132] (t,J=9.3Hz,1H),5.24(s,1H),5.17(s,1H),3.39(d,J=15.1Hz,1H),3.25(d,J=15.2Hz,1H),3.14(d,J=15.0Hz,1H),2.87(d,

[0133] J=15.0Hz,1H),1.66(s,3H),1.65(s,9H).

[0134] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.6, 159.2 (d, J = 239.4Hz), 148.1, 141.7, 140.6, 140.4, 128.4, 1 27.7,127.1(d,J=9.7Hz),126.6,125.3,117.2,116.1(d,J=9.1Hz),111.2(d,J=24.7Hz),103.6

[0135] (d,J=24.1Hz),102.9(d,J=3.9Hz),84.0,52.4,46.4,33.4,30.3,28.2.

[0136] 19 F NMR(376MHz, CDCl3)δ(ppm)-120.0.

[0137] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =95:5, flow rate 1.0mL / min, λ=254nm,

[0138] t1=5.67min,t2=6.37min.

[0139] High resolution: Calculated value: [M+Na] +:458.1738, measured value:458.1732.

[0140] Optical rotation: [α] D 25 =105.57 (c = 1.20 in CHCl3).

[0141] Example 8

[0142] Preparation of Compound I-8

[0143]

[0144] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-8 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-8, with a yield of 57% and an ee value (enantiomeric excess): 90%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0145] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.67 (d, J=8.9Hz, 1H), 7.11 (dd, J=

[0146] 6.6,3.0Hz,2H),6.98-6.91(m,3H),6.79(d,J=2.5Hz,1H),6.74(dd,J=9.0,2.6Hz,1H),5.2 3(s,1H),5.15(s,1H),3.83(s,3H),3.40(d,J=15.1Hz,1H),3.25(d,J=15.1Hz,1H),3.13(d,

[0147] J=14.9Hz,1H),2.85(d,J=14.9Hz,1H),1.66(s,3H),1.64(s,9H).

[0148] 13C NMR (100MHz, CDCl3) δ (ppm) 173.8, 155.7, 148.1, 141.9, 140.4, 140.0, 127.7, 126.9, 126.7, 126.4,125.3,117.0,115.7,111.3,102.9,101.4,83.4,55.6,52.4,46.4,33.2,30.4,28.2.

[0149] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=220nm,

[0150] t1=6.73min,t2=7.37min.

[0151] High resolution: Calculated value: [M+Na] + :470.1938, measured value:470.1932.

[0152] Optical rotation: [α] D 25 =42.47 (c = 1.06 in CHCl3).

[0153] Example 9

[0154] Preparation of Compound I-9

[0155]

[0156] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-9 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-9 with a yield of 68% and an ee value (enantiomeric excess) of 90%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0157] 1H NMR (400MHz, CDCl3) δ (ppm) 7.82-7.78 (m, 2H), 7.61 (dd, J = 8.3, 1.3Hz, 1H), 7.18-7.06 (m, 2H) ),6.96(dt,J=4.5,2.7Hz,3H),5.30(s,1H),5.16(s,1H),3.51(d,J=15.4Hz,1H),3.33(d,J=

[0158] 15.2Hz,1H),3.16(d,J=14.7Hz,1H),2.84(d,J=14.7Hz,1H),1.66(s,3H),1.64(s,9H),1.37(s,12H).

[0159] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.8, 148.2, 141.9, 140.6, 139.7, 134.4, 130.4, 127.9, 126.6, 12 5.7,125.3,124.7,117.6,114.2,103.5,83.8,83.7,52.6,46.3,32.8,30.5,28.2,24.9,24.9.

[0160] 11 B NMR (128MHz, CDCl3) δ (ppm) 5.1 (br).

[0161] Chiral HPLC: Chiral IG column, V 正己烷 / V 异丙醇 =90:10, flow rate 0.5mL / min, λ=254nm,

[0162] t1=14.06min,t2=15.47min.

[0163] High resolution: Calculated value: [M+Na] + :565.2721, measured value:565.2719.

[0164] Optical rotation: [α] D 25 =-29.37 (c = 1.80 in CHCl3).

[0165] Example 10

[0166] Preparation of Compound I-10

[0167]

[0168] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-10 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-10, with a yield of 64% and an ee value (enantiomeric excess): 94%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0169] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.19-7.13 (m, 2H), 7.08-7.00 (m, 3H), 6.79 (dd, J = 8.2, 2.4Hz, 1H) ,6.65(ddd,J=11.9,9.5,2.4Hz,1H),5.23(s,1H),5.17(s,1H),3.37-3.24(m,2H),3.17(d,J=

[0170] 14.8Hz,1H),2.86(d,J=14.8Hz,1H),1.66(s,3H),1.60(s,9H).

[0171] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.5, 158.7 (dd, J = 231.1, 10.8Hz), 149.2 (dd, J = 241.6, 13.7Hz), 146.6, 142.2, 141.3, 140.4, 130.0

[0172] (dd,J=10.9,5.1Hz),127.9,126.6,125.5,117.9,115.4(dd,J=

[0173] 9.4,2.1Hz),102.6(dd,J=4.2,1.7Hz),100.0(dd,J=28.4,25.5

[0174] Hz), 99.6 (dd, J = 23.8, 4.0Hz), 84.5, 52.7, 46.4, 32.4, 30.7, 27.8.

[0175] 19 F NMR (376MHz, CDCl3) δ (ppm) -113.6 (d, J = 5.6Hz), -117.4 (d, J = 5.6Hz).

[0176] Chiral HPLC: Chiral OZ column, V 正己烷 / V 异丙醇 =97:3, flow rate 0.5mL / min, λ=254nm,

[0177] t1=13.29min,t2=15.03min.

[0178] High resolution: Calculated value: [M+Na] + :476.1644, measured value:476.1645.

[0179] Optical rotation: [α] D 25 =-20.50 (c = 1.07, CHCl3).

[0180] Embodiment 11

[0181] Preparation of Compound I-11

[0182]

[0183] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-11 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-11, yield: 99%; ee value (enantiomeric excess): 88%, determined by separating the pure product through chiral high performance liquid chromatography.

[0184] 1H NMR (400MHz, CDCl3) δ (ppm) 7.44-7.36 (m, 1H), 7.13-7.04 (m, 4H), 6.92-6.84 (m, 1H), 5.23 (s, 1H), 5.11 (s, 1H), 3.60 (d, J=

[0185] 15.6Hz,1H),3.36(d,J=15.6Hz,1H),3.12(s,3H),3.08(d,J=

[0186] 14.5Hz,1H),2.77(d,J=14.5Hz,1H),1.67(s,3H).

[0187] 13 C NMR (100MHz, CDCl3) δ (ppm) 174.49,143.53,141.16,140.64,132.08,127.81,126.48,125.31 ,125.00,120.91,119.38,117.69,115.59,108.38,95.67,52.70,45.52,33.02,30.37,27.70.

[0188] Chiral HPLC: Chiral OD column, V 正己烷 / V 异丙醇 =95:5, flow rate 1.0mL / min, λ=254nm,

[0189] t1=7.22min,t2=8.20min.

[0190] High resolution: Calculated value: [M+H] + :332.1645, measured value:332.1645.

[0191] Optical rotation: [α] D 25 =28.40 (c = 1.40, CHCl3).

[0192] Example 12

[0193] Preparation of Compound I-12

[0194]

[0195] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-12 (0.1 mmol, 1.0 eq.) and substrate V-1 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-12 with a yield of 87% and an ee value (enantiomeric excess) of 86%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0196] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.46 (d, J=7.7Hz, 1H), 7.42 (t, J=

[0197] 7.7Hz,2H),7.32(t,J=7.5Hz,1H),7.18(d,J=7.3Hz,2H),7.12

[0198] (t,J=7.5Hz,2H),7.09-7.01(m,6H),5.29(s,1H),5.15(s,1H),3.62(d,J=15.8Hz,1H),3.50(d,J=15.8Hz,1H),3.17(d,J=

[0199] 14.1Hz,1H),2.83(d,J=14.1Hz,1H),1.58(s,3H).

[0200] 13 C NMR (100MHz, CDCl3) δ (ppm) 174.45,142.85,141.67,140.73,135.13,132.14,128.91,128.33,126.77,126 .49,126.42,125.68,125.36,121.68,120.44,117.80,116.59,109.83,97.30,52.89,46.41,31.42,30.49.

[0201] Chiral HPLC: Chiral OD column, V 正己烷 / V 异丙醇=95:5, flow rate 1.0mL / min, λ=254nm,

[0202] t1=5.44min,t2=6.15min.

[0203] High resolution: Calculated value: [M+Na] + :416.1621, measured value:416.1622.

[0204] Optical rotation: [α] D 25 =103.53 (c = 1.20, CHCl3).

[0205] Embodiment 13

[0206] Preparation of Compound I-13

[0207]

[0208] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-2 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-2 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-13, with a yield of 86% and an ee value (enantiomeric excess): 85%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0209] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.84-7.74 (m, 1H), 7.36-7.32 (m, 1H), 7.22-7.13 (m, 2H), 7.11-7 .03(m,2H),6.60(t,J=8.6Hz,2H),5.25(s,1H),5.15(s,1H),3.47(d,J=15.1Hz,1H),3.27(d,

[0210] J=15.0Hz,1H),3.06(d,J=15.0Hz,1H),2.88(d,J=15.0Hz,1H),1.66(s,3H),1.65(s,9H).

[0211] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.67, 161.11 (d, J = 246.4Hz), 148.07, 141.85, 139.52, 136.36, 132.13,127.12(d,J=7.9Hz),125.88,124.00,122.73,117.77,116.98,114.87,114.44(d,J=

[0212] 21.5Hz),102.86,83.83,51.64,46.91,33.34,30.04,28.23.

[0213] 19 F NMR(376MHz, CDCl3)δ(ppm)-115.7.

[0214] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =95:5, flow rate 1.0mL / min, λ=254nm,

[0215] t1=6.64min,t2=7.78min.

[0216] High resolution: Calculated value: [M+Na] + :458.1738, measured value:458.1732.

[0217] Optical rotation: [α] D 25 =-13.17 (c = 0.83, CHCl3).

[0218] Embodiment 14

[0219] Preparation of Compound I-14

[0220]

[0221] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-3 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-3 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-14, with a yield of 99% and an ee value (enantiomeric excess): 82%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0222] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.83-7.74 (m, 1H), 7.39-7.31 (m, 1H), 7.22-7.13 (m, 2H), 7.06-6 .97(m,2H),6.89-6.79(m,2H),5.25(s,1H),5.15(s,1H),3.48(d,J=15.0Hz,1H),3.26(d,J=

[0223] 15.0Hz,1H),3.04(d,J=15.1Hz,1H),2.88(d,J=15.1Hz,1H),1.66(s,12H).

[0224] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.5,148.0,141.8,139.5,139.0,132.3,132.2,127.7,126 .8,125.8,124.1,122.8,117.8,116.9,114.9,103.0,83.9,51.7,46.7,33.3,30.0,28.2.

[0225] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=220nm,

[0226] t1=5.70min,t2=6.73min.

[0227] High resolution: Calculated value: [M+Na]+ :474.1443, measured value:474.1443.

[0228] Optical rotation: [α] D 25 =-7.27 (c = 0.94, CHCl3).

[0229] Embodiment 15

[0230] Preparation of Compound I-15

[0231]

[0232] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-4 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-4 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-15, with a yield of 74% and an ee value (enantiomeric excess): 82%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0233] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.81-7.77 (m, 1H), 7.36-7.33 (m, 1H), 7.24-7.13 (m, 2H), 7.01-6.92 (m, 4H), 5.25 (s, 1H), 5.15

[0234] (s,1H),3.48(d,J=15.0Hz,1H),3.26(d,J=14.9Hz,1H),3.03

[0235] (d,J=15.2Hz,1H),2.87(d,J=15.0Hz,1H),1.67(s,9H),1.66

[0236] (s,3H).

[0237] 13C NMR (100MHz, CDCl3) δ (ppm) 173.4,148.0,141.8,139.5,139.4,132.3,130.6,127.2,125 .7,124.1,122.8,120.4,117.8,116.8,114.9,103.0,83.9,51.8,46.6,33.4,29.9,28.2.

[0238] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=220nm,

[0239] t1=6.03min,t2=7.42min.

[0240] High resolution: Calculated value: [M+Na] + :518.0937, measured value:518.0930.

[0241] Optical rotation: [α] D 25 =13.20 (c = 0.97, CHCl3).

[0242] Example 16

[0243] Preparation of Compound I-16

[0244]

[0245] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-5 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was obtained. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-16, with a yield of 81% and an ee value (enantiomeric excess): 86%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0246] 1H NMR (400MHz, CDCl3) δ (ppm) 7.67 (d, J=7.7Hz, 1H), 7.57 (d, J=

[0247] 8.4Hz,2H),7.34-7.28(m,1H),7.19-7.16(m,3H),7.15-7.09

[0248] (m,1H),5.26(s,1H),5.17(s,1H),3.84(s,3H),3.46(d,J=15.1

[0249] Hz,1H),3.28(d,J=15.1Hz,1H),3.12(d,J=15.1Hz,1H),2.90

[0250] (d,J=15.0Hz,1H),1.67(s,3H),1.66(s,9H).

[0251] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.3, 166.3, 148.0, 145.4, 141.5, 139.5, 132.0, 128.9, 128.1, 125 .8,125.3,124.1,122.8,117.9,117.2,114.8,103.3,84.0,52.4,51.9,46.5,33.1,30.1,28.2.

[0252] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=220nm,

[0253] t1=11.34min,t2=13.62min.

[0254] High resolution: Calculated value: [M+Na] + :498.1887, measured value:498.1882.

[0255] Optical rotation: [α] D 25 =5.50 (c = 0.31, CHCl3).

[0256] Embodiment 17

[0257] Preparation of Compound I-17

[0258]

[0259] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-6 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-6 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-17, with a yield of 66% and an ee value (enantiomeric excess): 88%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0260] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.70 (d, J=8.8Hz, 2H), 7.58 (d, J=

[0261] 8.2Hz,1H),7.34(d,J=7.3Hz,1H),7.24(d,J=8.9Hz,2H),7.18(td,J=7.5,1.2Hz,1H),7.12 (ddd,J=8.5,7.3,1.4Hz,1H),5.30(s,1H),5.21(s,1H),3.50(d,J=14.9Hz,1H),3.26(d,J=

[0262] 14.9Hz,1H),3.08(d,J=15.5Hz,1H),2.96(d,J=15.5Hz,1H),1.70(s,3H),1.68(s,9H).

[0263] 13 C NMR (100MHz, CDCl3) δ (ppm) 172.6,147.4,141.1,139.2,132.0,126.2,125.4,124 .6,123.1,122.6,118.1,117.3,114.7,103.6,84.5,52.1,46.7,33.9,29.8,28.2.

[0264] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0265] t1=10.42min,t2=11.84min.

[0266] High resolution: Calculated value: [M+Na] + :485.1683, measured value:485.1681.

[0267] Optical rotation: [α] D 25 =44.83 (c = 0.86, CHCl3).

[0268] Embodiment 18

[0269] Preparation of Compound I-18

[0270]

[0271] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-7 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-7 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-18, with a yield of 87% and an ee value (enantiomeric excess): 82%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0272] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.79 (d, J=7.9Hz, 1H), 7.33 (d, J=

[0273] 7.5Hz,1H),7.15(p,J=7.3Hz,2H),6.98(d,J=7.7Hz,2H),6.71(d,J=7.9Hz,2H),5.24(s,1H),5.15(s,1H),3.46(d,J=

[0274] 15.1Hz,1H),3.28(d,J=15.1Hz,1H),3.11(d,J=14.9Hz,1H),2.85(d,J=14.9Hz,1H),2.11(s,3H),1.65(d,J=1.2Hz,12H).

[0275] 13 C NMR (100MHz, CDCl3) δ (ppm) 174.1, 148.2, 142.2, 139.7, 137.5, 136.3, 132.4, 128.3, 126.1, 125.2,123.7,122.5,117.7,116.9,114.7,103.0,83.6,52.0,46.5,33.1,30.3,28.2,20.7.

[0276] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0277] t1=5.43min,t2=7.41min.

[0278] High resolution: Calculated value: [M+Na] + :454.1989, measured value:454.1987.

[0279] Optical rotation: [α] D 25 =-14.17 (c = 0.85, CHCl3).

[0280] Embodiment 19

[0281] Preparation of Compound I-19

[0282]

[0283] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-8 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was obtained. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-19, with a yield of 45% and an ee value (enantiomeric excess): 90%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0284] 1H NMR (400MHz, CDCl3) δ (ppm) 7.80 (dd, J = 6.1, 3.4Hz, 1H), 7.34

[0285] (dd,J=5.9,3.2Hz,1H),7.18(dq,J=7.2,4.1Hz,2H),6.94-

[0286] 6.87(m,2H),6.83(dd,J=10.3,2.4Hz,1H),6.63(tt,J=8.5,3.6

[0287] Hz,1H),5.27(s,1H),5.17(s,1H),3.47(d,J=15.1Hz,1H),3.29

[0288] (d,J=15.1Hz,1H),3.09(d,J=15.0Hz,1H),2.88(d,J=15.1

[0289] Hz,1H),1.66(s,3H),1.65(s,9H).

[0290] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.3, 162.1 (d, J = 246.3Hz), 148.2, 143.0 (d, J = 7.2Hz), 141.5, 139.4, 132.2, 129.1 (d, J = 8.2Hz), 125.9,124.0,122.7,121.1(d,J=3.1Hz),117.8,117.3,114.8,113.3(d,J=21.1Hz),112.6(d,J=23.0Hz),103.2,84.0,52.1(d,

[0291] J=1.6Hz),46.6,33.1,30.3,28.2.

[0292] 19 F NMR(376MHz, CDCl3)δ(ppm)-112.4.

[0293] Chiral HPLC: Chiral OZ column, V 正己烷 / V 异丙醇 =97:3, flow rate 0.5mL / min, λ=254nm,

[0294] t1=11.15min,t2=14.06min.

[0295] High resolution: Calculated value: [M+Na] +:458.1738, measured value:458.1735.

[0296] Optical rotation: [α] D 25 =-6.00 (c = 0.98, CHCl3).

[0297] Embodiment 20

[0298] Preparation of Compound I-20

[0299]

[0300] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-9 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-1 was obtained. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-20, with a yield of 76% and an ee value (enantiomeric excess): 88%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0301] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.86-7.76 (m, 1H), 7.39-7.31 (m, 1H), 7.24-7.13 (m, 2H), 7.09 (t, J=1.8Hz,1H),7.04(dt,J=7.1,1.9Hz,1H),6.98-6.85(m,2H),5.27(s,1H),5.17(s,1H),3.45

[0302] (d,J=15.2Hz,1H),3.31(d,J=15.2Hz,1H),3.10(d,J=15.0

[0303] Hz, 1H), 2.86 (d, J = 14.9Hz, 1H), 1.65 (s, 12H).

[0304] 13C NMR (100MHz, CDCl3) δ (ppm) 173.2, 148.2, 142.5, 141.5, 139.5, 134.0, 132.1, 128.8, 126.6, 125 .9,125.4,124.2,123.7,122.8,117.9,117.6,114.8,103.3,83.9,52.1,46.6,32.8,30.4,28.3.

[0305] Chiral HPLC: Chiral OZ column, V 正己烷 / V 异丙醇 =97:3, flow rate 0.5mL / min, λ=254nm,

[0306] t1=11.20min,t2=13.64min.

[0307] High resolution: Calculated value: [M+Na] + :474.1443, measured value:474.1440.

[0308] Optical rotation: [α] D 25 =-5.27 (c = 0.79, CHCl3).

[0309] Embodiment 21

[0310] Preparation of Compound I-21

[0311]

[0312] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-10 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-10 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-21, with a yield of 65% and an ee value (enantiomeric excess): 84%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0313] 1H NMR (400MHz, CDCl3) δ (ppm) 7.84-7.76 (m, 1H), 7.37-7.32 (m, 1H), 7.20-7.13 (m, 2H), 6.93 (t, J = 8.0Hz, 1H), 6.71 (d, J = 7.7

[0314] Hz,1H),6.59(t,J=2.1Hz,1H),6.45(dd,J=8.2,2.1Hz,1H),5.25(s,1H),5.16(s,1H),3.49 (d,J=15.0Hz,1H),3.36(s,3H),3.27(d,J=14.8Hz,1H),3.09(d,J=15.1Hz,1H),2.86(d,J=

[0315] 15.1Hz,1H),1.67(s,3H),1.65(s,9H).

[0316] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.7, 159.0, 148.2, 142.3, 141.8, 139.5, 132.3, 128.5, 126.0, 123.9, 122.5,118.3,117.8,116.6,114.8,111.6,111.4,103.1,83.7,54.9,52.2,46.5,33.6,30.2,28.2.

[0317] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0318] t1=5.76min,t2=6.31min.

[0319] High resolution: Calculated value: [M+Na] + :470.1938, measured value:470.1932.

[0320] Optical rotation: [α] D 25 =42.53 (c = 0.98, CHCl3).

[0321] Embodiment 22

[0322] Preparation of Compound I-22

[0323]

[0324] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-11 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-11 was used as the solvent. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-22 with a yield of 79% and an ee value (enantiomeric excess) of 81%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0325] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.80 (d, J=7.6Hz, 1H), 7.37 (d, J=

[0326] 7.2Hz,1H),7.25-7.16(m,2H),7.15(s,1H),7.06(d,J=8.5Hz,1H),6.99(d,J=8.4Hz,1H),5.28(s,1H),5.17(s,1H),3.48(d,J

[0327] =15.1Hz,1H),3.29(d,J=15.1Hz,1H),3.03(d,J=15.1Hz,1H),2.88(d,J=15.2Hz,1H),1.66(s,12H).

[0328] 13 C NMR (100MHz, CDCl3) δ (ppm) 172.9,148.0,141.4,140.7,139.4,132.2,132.1,130.6,129.3,127 .3,125.7,125.2,124.5,123.0,118.0,117.4,114.8,103.3,84.5,51.5,46.8,32.8,30.1,28.3.

[0329] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0330] t1=5.38min,t2=5.93min.

[0331] High resolution: Calculated value: [M+Na] + :508.1053, measured value:508.1056.

[0332] Optical rotation: [α] D 25 =18.70 (c = 0.83, CHCl3).

[0333] Embodiment 23

[0334] Preparation of Compound I-23

[0335]

[0336] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-12 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-12 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-23, with a yield of 58% and an ee value (enantiomeric excess): 83%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0337] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.63 (d, J=8.2Hz, 1H), 7.54 (d, J=

[0338] 8.6Hz,1H),7.46(s,1H),7.35-7.28(m,4H),7.29-7.22(m,2H),7.07(t,J=7.4Hz,1H),6.89(t,J=7.9Hz,1H),5.30(s,1H),5.24

[0339] (s,1H),3.51(d,J=15.1Hz,1H),3.35(d,J=15.2Hz,1H),3.25

[0340] (d,J=14.9Hz,1H),2.97(d,J=14.9Hz,1H),1.76(s,3H),1.60

[0341] (s,9H).

[0342] 13 C NMR (100MHz, CDCl3) δ (ppm) 174.0,148.0,142.2,139.7,137.6,132.8,132.0,131.7,127.6,127.3,127.0,125 .9,125.8,125.6,124.2,123.9,123.7,122.4,117.6,117.0,114.5,103.2,83.6,52.4,46.7,32.5,30.4,28.2.

[0343] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0344] t1=6.25min,t2=8.47min.

[0345] High resolution: Calculated value: [M+Na] + :490.1989, measured value:490.1988.

[0346] Optical rotation: [α] D 25 =28.50 (c = 1.13, CHCl3).

[0347] Embodiment 24

[0348] Preparation of Compound I-24

[0349]

[0350] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-13 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-13 was used. 石油醚 / V乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-24, with a yield of 99% and an ee value (enantiomeric excess): 81%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0351] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.85 (dq, J = 6.2, 3.9Hz, 1H), 7.29 (dt,

[0352] J=7.6,3.8Hz,1H),7.16(dtd,J=6.1,3.6,1.4Hz,4H),7.06-

[0353] 6.97(m,3H),5.23(s,1H),5.13(s,1H),3.45-3.23(m,3H),2.84

[0354] (d,J=14.2Hz,1H),2.13(dd,J=14.2,6.0Hz,1H),2.00(dd,J=

[0355] 14.2,4.6Hz,1H),1.65(s,9H),1.39-1.26(m,1H),0.77(d,J=

[0356] 6.7Hz,3H),0.42(d,J=6.7Hz,3H).

[0357] 13 C NMR (100MHz, CDCl3) δ (ppm) 174.1, 148.4, 141.9, 140.0, 138.1, 132.1, 127.6, 126.6, 126.6, 126.4 ,123.7,122.6,118.2,117.6,114.9,103.2,83.6,56.7,51.0,44.8,31.4,28.3,25.1,24.3,24.0.

[0358] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0359] t1=5.29min,t2=6.61min.

[0360] High resolution: Calculated value: [M+Na] + :482.2302, measured value:482.2298.

[0361] Optical rotation: [α]D 25 =95.57 (c = 1.02, CHCl3).

[0362] Embodiment 25

[0363] Preparation of Compound I-25

[0364]

[0365] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-1 (0.1 mmol, 1.0 eq.) and substrate V-14 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-14 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-25 with a yield of 81% and an ee value (enantiomeric excess) of 84%, as determined by separating the pure product by chiral high performance liquid chromatography.

[0366] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.82 (dt, J = 7.3, 3.6Hz, 1H), 7.34-

[0367] 7.26(m,4H),7.26(d,J=2.5Hz,2H),7.20-7.12(m,2H),7.11-

[0368] 7.06(m,2H),6.96(dt,J=4.5,2.6Hz,3H),5.24(s,1H),5.14(s,1H),4.38(s,2H),3.44-3.3 4(m,2H),3.32(t,J=6.6Hz,2H),3.22(d,J=14.4Hz,1H),2.82(d,J=14.4Hz,1H),2.17(dd,J=

[0369] 9.4,7.3Hz,2H),1.64(s,9H),1.50-1.33(m,1H),1.14-0.98(m,1H).

[0370] 13C NMR (100MHz, CDCl3) δ (ppm) 173.8,148.4,141.7,139.8,138.3,137.8,132.1,128.5,128.4,128.3,128.0,127.7,127.6,12 7.5,126.6,126.2,126.1,123.8,122.6,118.1,117.6,114.9,103.3,83.7,72.8,70.2,56.1,43.7,39.5,31.2,28.3,24.3.

[0371] Chiral HPLC: Chiral IC Column, V 正己烷 / V 异丙醇 =90:10, flow rate 1.0mL / min, λ=254nm,

[0372] t1=9.80min,t2=12.85min.

[0373] High resolution: Calculated value: [M+Na] + :574.2564, measured value:574.2566.

[0374] Optical rotation: [α] D 25 =48.90 (c = 1.08, CHCl3).

[0375] Embodiment 26

[0376] Preparation of Compound I-26

[0377]

[0378] Under argon protection, Pd2(dba)3·CHCl3 (5 mol%, 0.005 mmol, 5.12 mg), chiral ligand L1 (16 mol%, 0.016 mmol, 10.43 mg) and DCM (1 mL) were added to a 10 mL Shrek tube in sequence, and the reaction system was stirred at room temperature for 30 minutes. Substrate IV-8 (0.1 mmol, 1.0 eq.) and substrate V-12 (0.3 mmol, 3.0 eq.) were dissolved in DCM (1 mL) and then added to the reaction system. The reaction mixture was placed in a thermostat and stirred for 6 hours under 6 W Blue LEDs irradiation and 15 ° C. After the reaction, the solvent was evaporated and V-12 was used. 石油醚 / V 乙酸乙酯 =100:1 column chromatography to obtain the target product of formula I-26, with a yield of 55% and an ee value (enantiomeric excess): 82%, which was determined by separating the pure product through chiral high performance liquid chromatography.

[0379] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.64 (d, J=8.0Hz, 1H), 7.55 (d, J=

[0380] 8.6Hz,1H),7.48(d,J=1.9Hz,1H),7.36-7.25(m,4H),7.22(d,

[0381] J=9.0Hz,1H),6.78(d,J=2.5Hz,1H),6.49(dd,J=9.0,2.6Hz,1H),5.29(s,1H),5.24(s,1H), 3.81(s,3H),3.45(d,J=15.2Hz,1H),3.33(d,J=15.2Hz,1H),3.26(d,J=14.9Hz,1H),2.95(d,

[0382] J=14.8Hz,1H),1.75(s,3H),1.59(s,9H).

[0383] 13 C NMR (100MHz, CDCl3) δ (ppm) 173.9, 155.6, 148.0, 142.2, 140.2, 137.7, 132.7, 131.8, 127.6, 127.3, 127.0, 126.8, 126.7,125.8,125.7,124.2,123.7,117.1,115.5,111.6,103.2,101.4,83.4,55.8,52.5,46.7,32.4,30.5,28.2.

[0384] Chiral HPLC: Chiral OD column, V 正己烷 / V 异丙醇 =95:5, flow rate 0.5mL / min, λ=254nm,

[0385] t1=15.19min,t2=17.07min.

[0386] High resolution: Calculated value: [M+Na] + :520.2094, measured value:520.2090.

[0387] Optical rotation: [α] D 25 =-16.30 (c = 0.84, CHCl3).

[0388] Embodiment 27

[0389] Preparation of compound II-1

[0390]

[0391] Under argon protection, substrate I-1 (0.1 mmol, 1.0 eq.), Cs2CO3 (20 mol%) and THF (1 mL) were added to a 10 mL Shrek tube, and the reaction mixture was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, deuterated form was added to dissolve, and the dr value was determined by NMR. Then, V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula II-1, yield: 74%; dr value (diastereoisomer ratio):>19:1, the crude product before separation was 1 H NMR confirmed.

[0392] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.87 (d, J = 8.3Hz, 1H), 7.42–7.26

[0393] (m,6H),7.21(d,J=7.3Hz,1H),7.12(t,J=7.5Hz,1H),5.23(s,1H),5.05(s,1H),3.59(d,J=17.7 Hz,1H),3.01(ddd,J=20.1,17.6,2.5Hz,2H),2.40(d,J=15.8Hz,1H),1.62(s,9H),1.38(s,3H).

[0394] 13 C NMR (100MHz, CDCl3) δ (ppm) 206.4,172.9,148.7,140.1,138.3,130.1,128.9,128.8, 127.3,126.0,124.4,123.0,115.4,114.6,84.6,62.0,52.8,39.5,37.6,28.1,28.0.

[0395] High resolution: Calculated value: [M+Na] + :440.1832, measured value:440.1831.

[0396] Optical rotation: [α] D 25 =-92.03 (c = 1.40, CHCl3).

[0397] Embodiment 28

[0398] Preparation of compound II-2

[0399]

[0400] Under argon protection, substrate I-7 (0.1 mmol, 1.0 eq.), Cs2CO3 (20 mol%) and THF (1 mL) were added to a 10 mL Shrek tube, and the reaction mixture was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, deuterated form was added to dissolve, and the dr value was determined by NMR. Then, V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula II-2, yield: 72%; dr value (diastereoisomer ratio): 10:1, the crude product before separation was 1 H NMR confirmed.

[0401] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.87 (dd, J = 8.8, 4.5Hz, 1H), 7.42-

[0402] 7.27(m,6H),7.03(tdd,J=8.9,2.8,1.1Hz,1H),6.94(dd,J=8.0,2.1Hz,1H),5.26(s,1H),5. 09(s,1H),3.61(d,J=17.9Hz,1H),3.04(d,J=15.1Hz,1H),2.93(d,J=18.0Hz,1H),2.40(d,J=

[0403] 15.9Hz,1H),1.61(s,9H),1.39(s,3H).

[0404] 13 C NMR (100MHz, CDCl3) δ (ppm) 205.9, 172.4, 159.7 (d, J = 243.5Hz), 148.7, 139.9, 137.8, 136.2, 131 .4(d,J=8.2Hz),128.9,127.5,126.0,116.7(d,J=8.0Hz),115.3(d,J=22.7Hz),115.2,110.8(d,

[0405] J=25.3Hz),84.8,62.0,52.9,39.4,37.5,28.1,28.0.

[0406] 19 F NMR(376MHz, CDCl3)δ(ppm)-117.48.

[0407] High resolution: Calculated value: [M+Na] + :458.1738, measured value:458.1738.

[0408] Optical rotation: [α] D 25 =-56.70 (c = 0.55, CHCl3).

[0409] Embodiment 29

[0410] Preparation of compound II-3

[0411]

[0412] Under argon protection, substrate I-11 (0.1 mmol, 1.0 eq.), Cs2CO3 (20 mol%) and THF (1 mL) were added to a 10 mL Shrek tube, and the reaction mixture was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, deuterated form was added to dissolve, and the dr value was determined by NMR. Then, V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula II-2, yield: 76%; dr value (diastereoisomer ratio):>19:1, the crude product before separation was 1 H NMR confirmed.

[0413] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.42-7.36 (m, 4H), 7.30 (t, J = 7.6

[0414] Hz,2H),7.18(d,J=7.5Hz,1H),7.02(t,J=7.6Hz,1H),6.86(d,

[0415] J=7.8Hz,1H),5.21(s,1H),5.02(s,1H),3.60(d,J=18.0Hz,1H),3.20(s,3H),3.00(t,J=15.3Hz,2H),2.29(d,J=16.0Hz,1H),1.38(s,3H).

[0416] 13 C NMR (100MHz, CDCl3) δ (ppm) 207.0,174.8,144.2,140.3,138.9,131.4,128.8,128 .7,127.3,126.1,123.2,122.6,114.1,108.6,61.5,52.7,39.5,36.8,28.1,26.5.

[0417] High resolution: Calculated value: [M+Na] + :354.1465, measured value:354.1464.

[0418] Optical rotation: [α] D 25 =-249.27 (c = 1.10, CHCl3).

[0419] Embodiment 30

[0420] Preparation of compound II-4

[0421]

[0422] Under argon protection, substrate I-25 (0.1 mmol, 1.0 eq.), Cs2CO3 (20 mol%) and THF (1 mL) were added to a 10 mL Shrek tube, and the reaction mixture was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, deuterated form was added to dissolve, and the dr value was determined by NMR. Then, V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula II-2, yield: 73%; dr value (diastereoisomer ratio): 11:1, the crude product before separation was 1 H NMR confirmed.

[0423] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.87 (d, J = 8.2Hz, 1H, major), 7.80

[0424] (d,J=8.2Hz,1H,minor),7.40-7.29(m,9H,major+minor),7.26-7.24(m,2H,major+minor),7.17(d,J=7.5Hz,1H,

[0425] major),7.11(t,J=7.5Hz,1H,major),6.87(t,J=7.6Hz,1H,

[0426] minor),6.29(d,J=7.6Hz,1H,minor),5.25(s,1H,major+

[0427] minor),5.05(s,1H,major+minor),4.38(s,2H,major+minor),3.59(d,J=18.1Hz,1H,major),3.44(d,J=17.0Hz,1H,minor),3.31(t,J=6.6Hz,2H,major+m inor),2.98(dd,J=38.1,17.1Hz,2H,major),2.67(d,J=16.3Hz,1H,minor),2.57(d,J=16.3Hz,1H,minor),2.33(d,J=16.0Hz,1H,major),1.93-1.76(m,2H,

[0428] major+minor),1.62(s,9H,major+minor),1.46-1.37(m,1H,

[0429] major+minor),1.30-1.21(m,1H,major+minor).

[0430] 13 C NMR (100MHz, CDCl3) δ (ppm) 205.5, 172.9, 148.7, 140.1, 138.3, 138.2, 137.6, 129.7, 128.9, 128.8, 128.3, 127. 6,127.5,126.9,126.6,124.5,123.0,115.5,114.8,84.6,72.8,70.3,62.0,55.4,36.9,36.6,35.3,28.0,24.4.

[0431] High resolution: Calculated value: [M+Na] + :574.2564, measured value:574.2563.

[0432] Optical rotation: [α] D 25 =-75.97 (c = 1.08, CHCl3).

[0433] Embodiment 31

[0434] Preparation of compound II-5

[0435]

[0436] Under argon protection, substrate I-26 (0.1 mmol, 1.0 eq.), Cs2CO3 (20 mol%) and THF (1 mL) were added to a 10 mL Shrek tube, and the reaction mixture was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, deuterated form was added to dissolve, and the dr value was determined by NMR. Then, V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula II-2, yield: 83%; dr value (diastereoisomer ratio): 18:1, the crude product before separation was 1 H NMR confirmed.

[0437] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.83 (q, J = 9.8, 9.1Hz, 5H), 7.55-

[0438] 7.20(m,3H),6.84(d,J=7.1Hz,2H),5.27(s,1H),5.07(s,1H),3.78(s,3H),3.70(d,J=1 7.6Hz, 1H), 3.05 (t, J = 19.3Hz, 2H), 2.41 (d, J = 15.8Hz, 1H), 1.60 (s, 900H), 1.46 (s, 3H).

[0439] 13 C NMR (100MHz, CDCl3) δ (ppm) 206.5,172.9,156.6,148.8,138.2,137.8,133.5,133.4,132.5,131.3,128.6,128.2 ,127.5,126.0,126.0,124.8,124.3,116.2,114.8,112.3,110.9,84.3,62.2,55.6,53.0,39.9,37.7,28.0,27.9.

[0440] High resolution: Calculated value: [M+Na] + :520.2094, measured value:520.2093.

[0441] Optical rotation: [α] D 25 =-19.23 (c = 0.31, CHCl3).

[0442] Embodiment 32

[0443] Preparation of compound III-1

[0444]

[0445] Under argon protection, substrate I-1 (0.1 mmol, 1.0 eq.) and Acetone (1 mL) were added to a 10 mL Shrek tube, and the reaction system was cooled to 0°C. Freshly prepared DMDO solution (1.5 eq.) was then added, and the reaction mixture was slowly warmed to room temperature and stirred for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, deuterated form was added to dissolve, and the dr value was determined by NMR. Then, V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula III-1, yield: 69%; dr value (diastereoisomer ratio): 11:1, the crude product before separation was 1 H NMR confirmed.

[0446] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.90 (d, J = 8.2Hz, 1H, minor), 7.84

[0447] (d,J=8.2Hz,1H,major),7.50(d,J=7.8Hz,2H,minor),7.46(d,

[0448] J=7.8Hz,1H,minor),7.42-7.27(m,6H,major;4H,minor),7.20(t,J=7.6Hz,1H,minor), 7.10(d,J=4.3Hz,2H,major),5.15(s,1H,minor),5.14(s,1H,major),4.90(s,1H,major+

[0449] minor),3.50(d,J=15.6Hz,1H,minor),3.20(q,J=15.9Hz,2H,

[0450] major),2.95(dd,J=21.2,15.6Hz,2H,minor),2.73(d,J=16.2

[0451] Hz,1H,major),2.61(d,J=16.2Hz,1H,major),2.54(d,J=15.8

[0452] Hz,1H,minor),1.70(s,3H,major+minor),1.63(s,9H,major+

[0453] minor).

[0454] 13C NMR (100MHz, CDCl3) δ (ppm) 176.21, 170.50, 148.84, 143.53, 138.90, 138.66, 130.49, 128.78, 127.67 ,127.10,125.70,124.84,123.86,118.12,115.28,84.90,81.56,52.52,43.82,42.84,29.22,28.03.

[0455] High resolution: Calculated value: [M+Na] + :456.1781, measured value:456.1782.

[0456] Optical rotation: [α] D 25 =-74.07 (c = 1.60, CHCl3).

[0457] Embodiment 33

[0458] Preparation of compound III-2

[0459]

[0460] Under argon protection, add substrate I-2 (0.1mmol, 1.0eq.) and Acetone (1mL) to a 10mL Shrek tube, and cool the reaction system to 0°C. Then add freshly prepared DMDO solution (1.5eq.), slowly warm the reaction mixture to room temperature, and stir for 12 hours. After the reaction is completed, remove the solvent by rotary evaporation, add deuterated form to dissolve, determine the dr value by NMR, and then measure the V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula III-2, yield: 52%; dr value (diastereoisomer ratio): 10:1, the crude product before separation was 1 H NMR confirmed.

[0461] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.93 (s, 1H), 7.42-7.35 (m, 4H), 7.33

[0462] -7.28(m,1H),7.06(d,J=8.1Hz,1H),6.96(d,J=8.1Hz,1H),5.17(s,1H),4. 91(s,1H),3.30-3.03(m,2H),2.84-2.51(m,2H),1.68(s,3H),1.63(s,9H).

[0463] 13C NMR (100MHz, CDCl3) δ (ppm) 176.1, 170.2, 148.6, 143.3, 139.7, 138.4, 136.4, 128.8, 127 .2,125.8,125.8,125.0,124.9,118.8,116.0,85.4,80.8,52.7,43.9,42.8,29.1,28.0.

[0464] High resolution: Calculated value: [M+Na] + :490.1392, measured value:490.1388.

[0465] Optical rotation: [α] D 25 =-12.60 (c = 0.89, CHCl3).

[0466] Embodiment 34

[0467] Preparation of compound III-3

[0468]

[0469] Under argon protection, add substrate I-12 (0.1mmol, 1.0eq.) and Acetone (1mL) to a 10mL Shrek tube, and cool the reaction system to 0°C. Then add freshly prepared DMDO solution (1.5eq.), slowly warm the reaction mixture to room temperature, and stir for 12 hours. After the reaction is completed, remove the solvent by rotary evaporation, add deuterated form to dissolve, determine the dr value by NMR, and then measure the V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula III-3, yield: 62%; dr value (diastereoisomer ratio): 8:1, the crude product before separation was 1 H NMR confirmed.

[0470] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.51 (t, J = 7.5Hz, 2H), 7.47-7.37

[0471] (m,7H),7.30(t,J=7.2Hz,1H),7.23(t,J=7.9Hz,1H),7.16(d,

[0472] J=7.5Hz,1H),7.04(t,J=7.5Hz,1H),6.82(d,J=8.0Hz,1H),5.12(s,1H),4.93(s,1H),3.30(d,J=15.7Hz,1H),3.17(d,J=

[0473] 15.7Hz,1H),2.87(d,J=16.1Hz,1H),2.68(d,J=16.1Hz,1H),1.72(s,3H).

[0474] 13 C NMR (100MHz, CDCl3) δ (ppm) 176.6,171.8,143.8,142.5,139.4,133.6,130.1,129.6,128.8,1 28.6,128.3,127.1,126.3,125.8,124.2,123.6,117.7,109.8,82.2,52.6,44.0,42.9,29.3.

[0475] High resolution: Calculated value: [M+Na] + :432.1570, measured value:432.1569.

[0476] Optical rotation: [α] D 25 =-34.93 (c = 0.69, CHCl3).

[0477] Embodiment 35

[0478] Preparation of compound III-4

[0479]

[0480] Under argon protection, add substrate I-25 (0.1mmol, 1.0eq.) and Acetone (1mL) to a 10mL Shrek tube, and cool the reaction system to 0°C. Then add freshly prepared DMDO solution (1.5eq.), slowly warm the reaction mixture to room temperature, and stir for 12 hours. After the reaction is completed, remove the solvent by rotary evaporation, add deuterated form to dissolve, determine the dr value by NMR, and then measure the V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula III-4, yield: 56%; dr value (diastereoisomer ratio): 7:1, the crude product before separation was 1 H NMR confirmed.

[0481] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.90 (d, J = 8.3Hz, 1H, minor), 7.82

[0482] (d,J=8.2Hz,1H,major),7.49(d,J=7.8Hz,2H,minor),7.45(d,

[0483] J=7.6Hz,1H,minor),7.39-7.25(m,11H,major+minor),7.18

[0484] (t,J=7.5Hz,1H,minor),7.07(t,J=7.5Hz,1H,major),7.00(d,

[0485] J=7.6Hz,1H,major),5.15(s,1H,major+minor),4.86(s,1H,

[0486] major+minor),4.43(s,2H,major+minor),3.46(d,J=15.3Hz,1H,major),3.43-3.36(m,2H,major+minor),3.35-3.23(m,2H,minor),3.11(d,J=15.8Hz, 1H,major),2.86(d,J=15.9Hz,1H,minor),2.66(d,J=16.3Hz,1H,major),2.53(d,J=16.2Hz,1H,major),2.36(d,J=16.0Hz,1H,minor),2.22-1.90(m,2H,

[0487] major+minor),1.76-1.51(m,11H,major+minor).

[0488] 13 C NMR (100MHz, CDCl3) δ (ppm) 175.1, 170.5, 148.8, 141.0, 138.8, 138.5, 138.4, 130.4, 128.7, 128.6, 128.3, 127.8, 127. 6,127.4,127.1,126.6,126.4,124.8,123.9,118.2,115.2,84.8,81.2,72.7,70.3,56.0,42.5,40.8,40.0,28.0,25.2.

[0489] High resolution: Calculated value: [M+Na] + :590.2513, measured value:590.2513.

[0490] Optical rotation: [α] D 25 =-21.50 (c = 0.98, CHCl3).

[0491] Embodiment 36

[0492] Preparation of compound III-5

[0493]

[0494] Under argon protection, add substrate I-26 (0.1mmol, 1.0eq.) and Acetone (1mL) to a 10mL Shrek tube, and cool the reaction system to 0°C. Then add freshly prepared DMDO solution (1.5eq.), slowly warm the reaction mixture to room temperature, and stir for 12 hours. After the reaction is completed, remove the solvent by rotary evaporation, add deuterated form to dissolve, determine the dr value by NMR, and then measure the V 石油醚 / V 乙酸乙酯 =50:1 column chromatography to obtain the target product of formula III-4, yield: 51%; dr value (diastereoisomer ratio): 7:1, the crude product before separation was 1 H NMR confirmed.

[0495] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.87-7.82 (m, 4H), 7.74 (d, J = 8.9

[0496] Hz,1H),7.51-7.47(m,3H),6.82(dd,J=9.0,2.7Hz,1H),6.55

[0497] (d,J=2.7Hz,1H),5.22(s,1H),4.91(s,1H),3.51(s,3H),3.33-

[0498] 3.24(m,2H),2.73-2.59(m,2H),1.77(s,3H),1.62(s,9H).

[0499] 13 C NMR (100MHz, CDCl3) δ (ppm) 176.1, 170.7, 156.9, 148.9, 140.9, 138.7, 133.2, 132.3, 131.8, 128.6, 128.6, 12 7.9,127.5,126.4,126.2,124.3,118.6,116.4,115.9,109.4,84.7,81.6,55.4,52.8,43.8,43.0,29.3,28.0.

[0500] High resolution: Calculated value: [M+Na] + :536.2044, measured value:536.2044.

[0501] Optical rotation: [α] D25 =-8.00 (c = 0.40, CHCl3).

[0502] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and changes will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments.

Claims

1. A chiral indole octa-membered lactone compound, characterized in that: The chiral indole octa-membered lactone compound is a compound having a structure shown in formula (I), In formula (I), R 1 At least one selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen-substituted C1-C4 alkyl, C2-C4 carboxylate, pinacol borate and halogen; R 2 is hydrogen, tert-butyl carbonate, C1-C4 alkyl or phenyl; R 3 is a C1-C4 alkyl group or a benzyloxypropyl group; R 4 It is at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C2-C4 carboxylate, nitro and halogen, or together with the phenyl substituted therewith, forms a naphthyl group.

2. The chiral indole octa-membered lactone compound according to claim 1, wherein R 1 is hydrogen, 2-fluoro, 2-methoxy, 2-pinacol borate, 3-chloro, 3-fluoro, 3-trifluoromethyl, 3-carboxylic acid methyl ester, 3-methyl or 2,4-difluoro; R 2 is hydrogen, tert-butyl carbonate, methyl or phenyl; R 3 is methyl, isobutyl, 3-benzyloxypropyl; R 4 It is hydrogen, 7-fluoro, 7-chloro, 7-bromo, 7-carboxylic acid methyl ester, 7-nitro, 7-methyl, 8-methoxy, 8-fluoro, 8-chloro, 7,8-dichloro or together with the phenyl substituted therewith it forms a naphthyl group.

3. The method for synthesizing the chiral indole octa-membered lactone compound according to claim 1 or 2, characterized in that: The steps include: Under the protection of a first inert gas and in the presence of a first solvent, a compound having a structure represented by formula (IV), a compound having a structure represented by formula (V), a chiral ligand and a metal catalyst are mixed, and a dipolar cyclization reaction occurs under light conditions to obtain the compound having a structure represented by formula (I); In formula (IV), R 1 At least one selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen-substituted C1-C4 alkyl, C2-C4 carboxylate, pinacol borate and halogen; R 2 is hydrogen, tert-butyl carbonate, C1-C4 alkyl or phenyl; preferably, R 1 is hydrogen, 2-fluoro, 2-methoxy, 2-pinacol borate, 3-chloro, 3-fluoro, 3-trifluoromethyl, 3-carboxylic acid methyl ester, 3-methyl or 2,4-difluoro; R 2 is hydrogen, tert-butyl carbonate, methyl or phenyl; In formula (V), R 3 is a C1-C4 alkyl group or a benzyloxypropyl group; R 4 is at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C2-C4 carboxylate, nitro and halogen, or together with the phenyl substituted therewith forms a naphthyl group; preferably, R 3 is methyl, isobutyl, 3-benzyloxypropyl; R 4 It is hydrogen, 7-fluoro, 7-chloro, 7-bromo, 7-carboxylic acid methyl ester, 7-nitro, 7-methyl, 8-methoxy, 8-fluoro, 8-chloro, 7,8-dichloro or together with the phenyl substituted therewith it forms a naphthyl group.

4. The synthesis method according to claim 3, wherein Firstly, the metal catalyst and the chiral ligand are dissolved in the first solvent, stirred for 20 to 40 minutes, and then mixed with the compound having the structure shown in formula (IV) and the compound having the structure shown in formula (V).

5. The synthesis method according to claim 3, wherein The first inert gas is argon and / or nitrogen; The first solvent is dichloromethane and / or 1,2-dichloroethane; The metal catalyst is selected from at least one of tris(dibenzylideneacetone)dipalladium chloroform adduct, bis(dibenzylideneacetone)palladium and tetrakistriphenylphosphine palladium; The chiral ligand is selected from at least one of the compounds L1, L2, and L3 having the structure shown in formula (VI); The molar ratio of the compound having the structure represented by formula (IV), the compound having the structure represented by formula (V), the chiral ligand and the metal catalyst is 20-40:40-60:1-2:1; The illumination adopts visible light, the wavelength of the visible light is 350-456nm, and the light intensity is 3-15W; The conditions of the dipolar cyclization reaction include: temperature of 0 to 40° C. and time of 2 to 10 hours.

6. A spirooxidoindole compound, characterized in that The spiro-oxidized indole compound is a product obtained by rearrangement of the chiral indole octa-membered lactone compound according to claim 1 or 2; The spiro oxidized indole compound is a compound having a structure represented by formula (II) or a compound having a structure represented by formula (III); In formula (II)-(III), R 1 At least one selected from hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen-substituted C1-C4 alkyl, C2-C4 carboxylate, pinacol borate and halogen; R 2 is hydrogen, tert-butyl carbonate, C1-C4 alkyl or phenyl; R 3 is a C1-C4 alkyl group or a benzyloxypropyl group; R 4 It is at least one of hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C2-C4 carboxylate, nitro and halogen, or together with the phenyl substituted therewith, forms a naphthyl group.

7. The spirooxidine compound according to claim 6, wherein In formula (II), R 1 is hydrogen, 2-fluoro or 2-methoxy; R 2 is hydrogen, tert-butyl carbonate or methyl; R 3 is methyl or 3-benzyloxypropyl; R 4 is hydrogen or, together with the phenyl group substituted by it, forms a naphthyl group; In formula (III), R 1 is hydrogen, 2-methoxy or 3-chloro; R 2 is hydrogen, tert-butyl carbonate or phenyl; R 3 is methyl or 3-benzyloxypropyl; R 4 It is hydrogen or, together with the phenyl group it replaces, forms a naphthyl group.

8. The method for synthesizing the spirooxidoindole compound according to claim 6 or 7, characterized in that: The steps include: The compound having the structure shown in formula (I) is rearranged under the action of a catalyst to obtain a compound having the structure shown in formula (II) or a compound having the structure shown in formula (III).

9. The synthesis method according to claim 8, wherein The synthesis method of the compound having the structure shown in formula (II) comprises the following steps: Under the protection of a second inert gas and in the presence of a second solvent, reacting the compound having the structure represented by formula (I) with the first catalyst to obtain the compound having the structure represented by formula (II); Preferably, the second inert gas is argon and / or nitrogen; the second solvent is selected from at least one of tetrahydrofuran, dichloromethane and acetonitrile; the first catalyst is selected from at least one of cesium carbonate, potassium phosphate and 4-dimethylaminopyridine; the molar ratio of the compound having the structure represented by formula (I) to the first catalyst is 1-10:1; the reaction conditions include: temperature of 0 to 40°C and time of 8 to 20 hours.

10. The synthesis method according to claim 8, wherein The synthesis method of the compound having the structure shown in formula (II) comprises the following steps: Under a third inert gas protection condition and in the presence of a third solvent, reacting the compound having the structure represented by formula (I) with a second catalyst to obtain the compound having the structure represented by formula (II); Preferably, the third inert gas is argon and / or nitrogen; the third solvent is selected from at least one of acetone, tetrahydrofuran and dichloromethane; the second catalyst is selected from at least one of dimethyldioxirane, meta-chloroperbenzoic acid and potassium peroxymonosulfonate; the molar ratio of the compound having the structure represented by formula (I) and the second catalyst is 1-0.5:1; the reaction conditions include: temperature of -10 to 10°C and time of 8 to 20 hours.

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