Chiral sulfoxide ester compound and preparation method thereof

Abstract

The application provides a chiral sulfoxide ester compound and a preparation method thereof, and relates to the field of compound synthesis.The structural general formula of the chiral sulfoxide ester compound is shown as formula (1).The application discloses that the asymmetric sulfinylation of sodium sulfinic acid on alcohol is realized by using a quinine or quinidine small molecule catalyst to prepare a chiral sulfoxide ester compound, the method has wide reaction substrates, and has an excellent yield of up to 84% and an enantioselectivity of up to 99%.

Description

Technical Field

[0001] This invention relates to the field of compound synthesis, and in particular to a chiral sulfoxide compound and its preparation method. Background Technology

[0002] Sulfur stereocenters are widely found in natural products, pharmaceuticals, and agrochemicals. Due to the importance of stereochemistry in biomolecular recognition and toxicity, the absolute configuration of sulfur stereocenters has a significant impact on their biological activity. Furthermore, enantiomeric sulfur stereoframes have extensive applications in asymmetric organic synthesis, such as as chiral cofactors, ligands, and catalysts. Sulfinates are a particularly important class of stereosulfur chiral centers, often serving as crucial chiral structural units, and can be readily derivatized in a stereospecific manner, enabling the preparation of various chiral S-containing stereoderives. Therefore, the preparation of chiral sulfoxide esters has attracted considerable attention. Efficient methods for constructing S-chiral molecules typically rely on diastereoselective methods utilizing stoichiometric chiral reagents. Despite recent significant progress (J. Am. Chem. Soc. 2005, 127, 1374-1375; Nature 2022, 604, 298-303; Nat. Chem. 2023 15, 185-193; Nat. Catal. 2023 6, 487-494.), stereoselective synthesis controlled by organocatalysts remains a considerable challenge. In particular, research on the use of small-molecule catalysts to control the construction of sulfur stereocenters with high enantioselectivity is limited. Summary of the Invention

[0003] To address the aforementioned problems, this invention provides a chiral sulfoxide ester compound and its preparation method. This invention designs and synthesizes a class of chiral sulfoxide ester compounds with novel structures, good substrate universality, and high enantioselectivity. This invention focuses on the highly enantioselective asymmetric sulfinization of sulfonates and alcohols using the small-molecule catalyst quinine, and develops a novel organocatalytic asymmetric condensation method to prepare chiral sulfoxide ester compounds. This method has the advantages of simple operation, easy substrate preparation, and excellent yield and stereoselectivity.

[0004] To achieve the above objectives, the present invention provides the following technical solution:

[0005] This invention provides a chiral sulfoxide ester compound, the general structural formula of which is shown in formula (1):

[0006]

[0007] Among them, the sulfur atom marked with an asterisk (*) is a chiral sulfur atom;

[0008] R 1The following are possible meanings: phenyl, tolyl, ethylphenyl, biphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-methoxyphenyl, 2-trifluoromethoxyphenyl, 2,5-dimethoxyphenyl, 4-nitro, naphthyl, cyclohexyl, butyl, thienyl, 5-chlorothienyl, 5-bromothienyl, quinolinyl, pyridyl, or 5-bromopyridyl.

[0009] R 2 It is isopropyl, tert-butyl, benzyl, cyclobutyl, cyclohexyl, cycloheptyl, (1R,3S,5R,7R)-adamantane-2-yl, methoxypropane-2-yl, tetrahydrofuranyl, (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl, 2-((R)-4-methylcyclohexyl-3-en-1-yl)propyl-2-yl, (3S,5S,8R,10S,13S)-10,13-dimethyl-17-oxohexadecyl-1H-cyclopentyl-3-yl, 17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecylhydropenten-1H-cyclopentylphenanthrene-3-yl, butyl, or ethyl.

[0010] The present invention also provides a method for preparing the chiral sulfoxide ester compound described above, comprising the following steps:

[0011] 1) Under a nitrogen atmosphere, quinine or quinidine, sodium sulfite, 2-methyl-6-nitrobenzoic anhydride, carbonate and chloroform are mixed and stirred to obtain a stirred mixture;

[0012] The carbonates include rubidium carbonate, sodium carbonate, potassium carbonate, or potassium phosphate;

[0013] 2) The mixture obtained in step 1) is mixed with alcohol and stirred to obtain a chiral sulfoxide ester compound.

[0014] Preferably, in step 1), the volume ratio of quinine (molar), sodium sulfite (molar), 2-methyl-6-nitrobenzoic anhydride (molar), carbonate (molar), and chloroform (volume) is 0.02 mmol:0.1 mmol:0.11 mmol:0.11 mmol:1.5 ml.

[0015] Preferably, the stirring conditions in step 1) include: a temperature of 25–30°C and a time of 1 hour.

[0016] Preferably, the molar ratio of alcohol in step 2) to quinine in step 1) is 0.105:0.02.

[0017] Preferably, the alcohol comprises one or more of methanol, ethanol, isopropanol, tert-butanol, benzyl alcohol, cyclobutanol, cyclohexanol, cycloheptanol, 2-adamantanol, methoxy-propanol, D / L menthol, terpineol, androgensone and pregnenolone.

[0018] Preferably, the stirring conditions in step 2) include: a temperature of 0°C and a time of 48 hours.

[0019] This invention also provides a method for preparing chiral sulfoxide derivatives using the chiral sulfoxide ester compounds described above, comprising the following steps:

[0020] I. Under nitrogen protection, (2-bromophenyl)-diphenylphosphoric acid, tetrahydrofuran and n-butyllithium are mixed to obtain a mixture;

[0021] The mass ratio of (2-bromophenyl)-diphenylphosphine, the volume ratio of tetrahydrofuran, and the volume ratio of n-butyllithium is 37.5 mg: 1 ml: 69 μl.

[0022] II. The mixture obtained in step I is mixed and stirred with a toluene solution containing the chiral sulfoxide ester compound described in the above technical solution to obtain a chiral sulfoxide derivative.

[0023] The mass ratio of the chiral sulfoxide compound to (2-bromophenyl)-diphenylphosphoric acid in the toluene solution was 19.8:37.5.

[0024] This invention also provides a method for preparing chiral sulfoxide derivatives using the chiral sulfoxide ester compounds described above, comprising the following steps:

[0025] A. Under nitrogen protection, 2-methylpyridine, tetrahydrofuran and n-butyllithium are mixed to obtain a mixture;

[0026] The mass ratio of 2-methylpyridine, the volume of tetrahydrofuran, and the volume ratio of n-butyllithium is 23.3 mg: 1 ml: 156.3 μl;

[0027] B. The mixture obtained in step A is mixed and stirred with a tetrahydrofuran solution containing the chiral sulfoxide ester compound described in the above technical solution to obtain a chiral sulfoxide ester derivative.

[0028] The mass ratio of chiral sulfoxide esters to 2-methylpyridine in the tetrahydrofuran solution is 19.8:23.3.

[0029] The present invention also provides a method for preparing chiral sulfoxide derivatives using the chiral sulfoxide compounds described in the above technical solution, comprising the following steps:

[0030] The chiral sulfoxide ester compound described in the above technical solution is mixed with tetrahydrofuran to obtain a mixture;

[0031] The mixture was mixed and stirred with a magnesium bromide reagent to obtain a chiral sulfoxide derivative.

[0032] The magnesium bromide reagents include methyl magnesium bromide, tert-butyl magnesium bromide, phenyl magnesium bromide, or isopropenyl magnesium bromide.

[0033] The beneficial effects of this invention are as follows:

[0034] This invention utilizes readily available sodium sulfite to asymmetricly condense alcohols, achieving asymmetric sulfinylation of various alcohols. A unique racemic mixed anhydride is used as the key reaction intermediate, and a naturally occurring, inexpensive quinine catalyst, requiring no further structural modification, is selected to control the formation of S-stereocenters from SO bonds with high yield and high enantioselectivity. This method is simple to operate, the substrates are easy to prepare, and it exhibits excellent yield and stereoselectivity, covering a broad substrate range. It constructs chiral sulfoxide derivatives with high optical purity. Detailed Implementation

[0035] This invention provides a chiral sulfoxide ester compound, the general structural formula of which is shown in formula (1):

[0036]

[0037] Among them, the sulfur atom marked with an asterisk (*) is a chiral sulfur atom;

[0038] R 1 The following are possible meanings: phenyl, tolyl, ethylphenyl, biphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-methoxyphenyl, 2-trifluoromethoxyphenyl, 2,5-dimethoxyphenyl, 4-nitro, naphthyl, cyclohexyl, butyl, thienyl, 5-chlorothienyl, 5-bromothienyl, quinolinyl, pyridyl, or 5-bromopyridyl.

[0039] R 2It is isopropyl, tert-butyl, benzyl, cyclobutyl, cyclohexyl, cycloheptyl, (1R,3S,5R,7R)-adamantane-2-yl, methoxypropane-2-yl, tetrahydrofuranyl, (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl, 2-((R)-4-methylcyclohexyl-3-en-1-yl)propyl-2-yl, (3S,5S,8R,10S,13S)-10,13-dimethyl-17-oxohexadecyl-1H-cyclopentyl-3-yl, 17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecylhydropenten-1H-cyclopentylphenanthrene-3-yl, butyl, or ethyl.

[0040] In this invention, the chiral sulfoxide ester compound preferably has any of the following structures:

[0041]

[0042] The present invention also provides a method for preparing the chiral sulfoxide ester compound described above, comprising the following steps:

[0043] 1) Under a nitrogen atmosphere, quinine or quinidine, sodium sulfite, 2-methyl-6-nitrobenzoic anhydride, carbonate and chloroform are mixed and stirred to obtain a stirred mixture;

[0044] The carbonates include rubidium carbonate, sodium carbonate, potassium carbonate, or potassium phosphate;

[0045] 2) The mixture obtained in step 1) is mixed with alcohol and stirred to obtain a chiral sulfoxide ester compound.

[0046] In this invention, the general reaction formula and process for preparing chiral sulfoxide ester compounds are as follows:

[0047]

[0048] In this invention, quinine, sodium sulfite, 2-methyl-6-nitrobenzoic anhydride, rubidium carbonate, and chloroform are mixed and stirred under a nitrogen atmosphere to obtain a stirred mixture. In this invention, the preferred volume ratio of the molar amounts of quinine, sodium sulfite, 2-methyl-6-nitrobenzoic anhydride, carbonate, and chloroform is 0.02 mmol:0.1 mmol:0.11 mmol:0.11 mmol:1.5 ml. In this invention, the preferred stirring conditions include a temperature of 25–30 °C and a time of 1 hour. In this invention, the 2-methyl-6-nitrobenzoic anhydride in situ activates the sodium sulfite to form a mixed anhydride intermediate, and quinine activates the anhydride intermediate.

[0049] This invention involves mixing and stirring the obtained mixture with an alcohol to obtain a chiral sulfoxide ester compound. In this invention, the molar ratio of the alcohol to quinine is preferably 0.105:0.02. In this invention, the alcohol preferably includes one or more of methanol, ethanol, isopropanol, tert-butanol, benzyl alcohol, cyclobutanol, cyclohexanol, cycloheptanol, 2-adamantaneol, methoxy-propanol, D / L menthol, terpineol, androstenolol, and pregnenolone. In this invention, the stirring conditions preferably include a temperature of 0°C and a time of 48 hours.

[0050] This invention also provides a method for preparing chiral sulfoxide derivatives using the chiral sulfoxide compounds described above, comprising the following steps:

[0051] I. Under nitrogen protection, (2-bromophenyl)-diphenylphosphine, tetrahydrofuran and n-butyllithium are mixed to obtain a mixture; the mass ratio of (2-bromophenyl)-diphenylphosphine, the volume ratio of tetrahydrofuran and the volume ratio of n-butyllithium are 37.5 mg: 1 ml: 69 μl.

[0052] II. The mixture obtained in step I is mixed and stirred with a toluene solution containing the chiral sulfoxide ester compound described in the above technical solution to obtain a chiral sulfoxide ester derivative; the mass ratio of the chiral sulfoxide ester compound to (2-bromophenyl)-diphenylphosphoric acid in the toluene solution is 19.8:37.5.

[0053] This invention also provides a method for preparing chiral sulfoxide derivatives using the chiral sulfoxide ester compounds described above, comprising the following steps:

[0054] A. Under nitrogen protection, 2-methylpyridine, tetrahydrofuran, and n-butyllithium are mixed to obtain a mixture; the mass ratio of 2-methylpyridine, the volume of tetrahydrofuran, and the volume ratio of n-butyllithium are 23.3 mg: 1 ml: 156.3 μl.

[0055] B. The mixture obtained in step A is mixed and stirred with a tetrahydrofuran solution containing the chiral sulfoxide ester compound described in the above technical solution to obtain a chiral sulfoxide derivative; the mass ratio of the chiral sulfoxide ester compound to 2-methylpyridine in the tetrahydrofuran solution is 19.8:23.3.

[0056] This invention also provides a method for preparing chiral sulfoxide derivatives using the chiral sulfoxide ester compounds described above, comprising the following steps:

[0057] The chiral sulfoxide ester compound described in the above technical solution is mixed with tetrahydrofuran to obtain a mixture;

[0058] The mixture was mixed with a magnesium bromide reagent and stirred to obtain a chiral sulfoxide derivative.

[0059] The magnesium bromide reagents include methyl magnesium bromide, tert-butyl magnesium bromide, phenyl magnesium bromide, or isopropenyl magnesium bromide.

[0060] To further illustrate the present invention, the following detailed description is provided in conjunction with embodiments, but these should not be construed as limiting the scope of protection of the present invention.

[0061] Example 1

[0062] (1) Asymmetric synthetic route of chiral sulfoxide esters

[0063]

[0064] The preparation method and conditions are as follows:

[0065] Under a nitrogen atmosphere, quinine E (0.02 mmol, 20 mol%, 6.5 mg), sulfinate 1 (0.10 mmol), 3c (0.1 mmol, 1.1 equivalent, 37.9 mg), rubidium carbonate (0.11 mmol, 1.1 equivalent, 25.4 mg), and chloroform (1.5 mL) were added to a 100.0 mL screw-cap vial equipped with a magnetic stir bar. The mixture was stirred at room temperature for 1 hour, and then alcohol 2 (0.105 mmol, 1.05 equivalent) was added to the reaction. The resulting solution was stirred continuously at 0 °C for 48 hours until the substrate was completely consumed (monitored by TLC). The reaction was quenched with a saturated aqueous sodium carbonate solution and extracted with DCM (3 x 10 mL). The mixture was concentrated under vacuum and purified by rapid column chromatography (petroleum ether / ethyl acetate = 5:1) to give the desired products 4 and 5.

[0066] The synthesized compounds were characterized experimentally as follows:

[0067] (R)-Isopropyl benzenesulfinate (4c)

[0068] Substituent R 1 It is a phenyl group, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0069] Colorless oil (15.5 mg, 84% yield).

[0070] 1 H NMR (400MHz, CDCl3) δ7.74-7.69(m,2H),7.55-7.51(m,3H),4.66-4.57(m,1H),1.39(d,J=6.2Hz,3H),1.25(d,J=6.3Hz,3H).

[0071] 13C NMR (100MHz, CDCl3) δ145.8,132.1,129.1,125.2,73.1,24.1,23.9ppm.

[0072] HRMS(ESI,m / z):calculated for C9H 12 O2SNa + [M+Na] + :207.0450,found:207.0452.

[0073] [α] 25 D = +63.3 (c = 0.3 in CHCl3).

[0074] HPLC analysis: 97:3e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 1.0mL / min), Rt (major) = 5.4min, Rt (minor) = 6.0min.

[0075] (R)-4-methylbenzenesulfinate isopropyl ester (4d)

[0076] Substituent R 1 It is toluene, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0077] Colorless oil (16.1 mg, 81% yield).

[0078] 1 H NMR (400MHz, CDCl3) δ7.60 (d, J = 8.2Hz, 2H), 7.32 (d, J = 7.7Hz, 2H), 4.70-4.51 (m, 1H), 2.42 (s, 3H), 1.38 (d, J = 6.2Hz, 3H), 1.24 (d, J = 6.3Hz, 3H).

[0079] 13 C NMR (100MHz, CDCl3) δ142.7,142.6,129.8,125.2,72.9,24.1,23.9,21.6ppm.

[0080] HRMS(ESI,m / z):calculated for C 10 H 14 O2SNa + [M+Na] + :221.0607,found:221.0609.

[0081] [α] 25 D = +181.6 (c = 0.2, CHCl3).

[0082] HPLC analysis: 97:3e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=24.7min, Rt(minor)=28.1min.

[0083] (R)-4-Ethylbenzenesulfinic acid isopropyl ester (4e)

[0084] Substituent R 1 It is ethylphenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0085] Colorless oil (17.2 mg, 81% yield).

[0086] 1 H NMR (400MHz, CDCl3) δ7.62(d,J=8.3Hz,2H),7.35(d,J=8.4Hz,2H),4.69-4.52(m ,J=6.5Hz,1H),2.72(q,J=7.6Hz,2H),1.39(d,J=6.2Hz,3H),1.29-1.22(m,6H).

[0087] 13 C NMR (100MHz, CDCl3) δ148.8,142.9,128.6,125.2,72.9,28.9,24.1,23.9,15.5ppm.

[0088] HRMS(ESI,m / z):calculated for C 11 H 16 O2SNa + [M+Na] + :35.0763,found:235.0765.

[0089] [α] 25 D = +63.1 (c = 0.4, CHCl3).

[0090] HPLC analysis: 97:3e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 17.9min, Rt (minor) = 19.2min.

[0091] (R)-[1,1'-biphenyl]-4-isopropyl sulfinate (4f)

[0092] Substituent R 1 It is a biphenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0093] Colorless oil (18.8 mg, 72% yield).

[0094] 1 H NMR (400MHz, CDCl3) δ7.83-7.70(m,3H),7.67-7.57(m,2H),7.52-7.44(m,2H),7. 44-7.36(m,1H),4.80-4.56(m,1H),1.42(d,J=6.2Hz,3H),1.30(d,J=6.3Hz,3H).

[0095] 13 C NMR (100MHz, CDCl3) δ145.1,144.5,139.9,129.1,128.3,127.9,127.5,125.7,73.3,24.1,23.9ppm.

[0096] HRMS(ESI,m / z):calculated for C 15 H 16 O2SNa + [M+Na] + :283.0763,found:283.0764.

[0097] [α] 25 D = +59.8 (c = 0.45, CHCl3).

[0098] HPLC analysis: 97:3e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 21.8min, Rt (minor) = 26.9min.

[0099] (R)-4-methoxybenzenesulfinic acid isopropyl ester (4g)

[0100] Substituent R 1 It is 4-methoxyphenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0101] Colorless oil (16.9 mg, 79% yield).

[0102] 1 H NMR (400MHz, CDCl3) δ7.64(d,J=8.8Hz,2H),7.01(d,J=8.8Hz,2H),4.68-4.49(m,1H),3.86(s,3H),1.37(d,J=6.2Hz,3H),1.24(d,J=6.2Hz,3H).

[0103] 13 C NMR (100MHz, CDCl3) δ162.6,137.3,127.0,114.4,72.5,55.7,24.1,23.9ppm.

[0104] HRMS(ESI,m / z):calculated for C 10 H 14 NaO3S + [M+Na] + :237.0556,found:237.0556.

[0105] [α] 25 D = +71.3 (c = 0.3 in CHCl3).

[0106] HPLC analysis: 97:3e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1mL / min), Rt (major) = 39.1min, Rt (minor) = 56.5min.

[0107] (R)-4-fluorobenzenesulfinic acid isopropyl ester (4h)

[0108] Substituent R 1 It is 4-fluorophenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0109] Colorless oil (16.8 mg, 83% yield).

[0110] 1H NMR (400MHz, CDCl3) δ7.81-7.60(m,2H),7.21(t,J=8.6Hz,2H),4.71-4.53(m,1H),1.39(d,J=6.2Hz,3H),1.26(d,J=6.3Hz,3H).

[0111] 13 C NMR (100MHz, CDCl3) δ165.0 (d, J = 252.3Hz), 141.6 (d, J = 3.1Hz), 127.7 (d, J = 8.8Hz), 116.4 (d, J = 22.5Hz), 73.3, 24.0, 23.9ppm.

[0112] 19 F NMR (376MHz, CDCl3) δ-107.3ppm.

[0113] HRMS(ESI,m / z):calculated for C9H 11 FO2S + [M+Na] + :225.0356,found:225.0358.

[0114] [α] 25 D = +32.1 (c = 0.5 in CHCl3).

[0115] HPLC analysis: 95:5e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=13.8min, Rt(minor)=14.6min.

[0116] (R)-4-chlorobenzenesulfinate isopropyl ester (4i)

[0117] Substituent R 1 It is 4-chlorophenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0118] Colorless oil (19.3 mg, 88% yield).

[0119] 1 H NMR (400MHz, CDCl3) δ7.65(d,J=8.6Hz,2H),7.50(d,J=8.6Hz,2H),4.71-4.52(m,1H),1.39(d,J=6.2Hz,3H),1.26(d,J=6.3Hz,3H).

[0120] 13 C NMR (100MHz, CDCl3) δ144.3,138.4,129.4,126.8,73.5,24.0,23.9ppm.

[0121] HRMS(ESI,m / z):calculated for C9H 11 ClNaO2S + [M+Na] + :241.0060,found:241.0062.

[0122] [α] 25 D = +41.8 (c = 0.3 in CHCl3).

[0123] HPLC analysis: 96:4e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 10.8min, Rt (minor) = 11.8min.

[0124] (R)-4-bromobenzenesulfinic acid isopropyl ester (4j)

[0125] Substituent R 1 It is 4-bromophenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0126] Colorless oil (21.3 mg, 81% yield).

[0127] 1 H NMR (400MHz, CDCl3) δ7.67 (d, J = 8.5Hz, 2H), 7.58 (d, J = 8.5Hz, 2H), 4.67-4.54 (m, 1H), 1.39 (d, J = 6.2Hz, 3H), 1.26 (d, J = 6.3Hz, 3H).

[0128] 13 C NMR (100MHz, CDCl3) δ144.9,132.3,126.9,126.8,73.4,24.0,23.8ppm.

[0129] HRMS(ESI,m / z):calculated for C9H 11 BrO2SNa + [M+Na] +:284.9555,found:284.9557.

[0130] [α] 25 D = +59.6 (c = 0.45 in CHCl3).

[0131] HPLC analysis: 95:5e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 12.6min, Rt (minor) = 14.3min.

[0132] (R)-4-Isopropyl iodobenzenesulfinate (4kJ)

[0133] Substituent R 1 It is 4-iodophenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0134] Yellow solid (24.5 mg, 79% yield).

[0135] 1 H NMR (400MHz, CDCl3) δ7.88 (d, J = 8.4Hz, 1H), 7.43 (d, J = 8.4Hz, 1H), 4.68-4.54 (m, 1H), 1.38 (d, J = 6.2Hz, 3H), 1.26 (d, J = 6.3Hz, 3H).

[0136] 13 C NMR (100MHz, CDCl3) δ145.7,138.2,126.8,99.1,73.5,24.0,23.9ppm.

[0137] HRMS(ESI,m / z):calculated for C9H 11 IO2SNa + [M+Na] + :332.9417,found:332.9418.

[0138] [α] 25 D =+49.8.3 (c=0.6in CHCl3).

[0139] HPLC analysis: 95:5e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 11.3min, Rt (minor) = 12.6min.

[0140] (R)-2-methoxybenzenesulfinic acid isopropyl ester (4l)

[0141] Substituent R 1 It is 2-methoxyphenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at room temperature;

[0142] Pale yellow oil (18.4 mg, 86% yield).

[0143] 1 H NMR (400MHz, CDCl3) δ7.64(d,J=8.8Hz,2H),7.01(d,J=8.8Hz,2H),4.59(m,1H),3.86(s,3H),1.37(d,J=6.2Hz,3H),1.24(d,J=6.4Hz,3H).

[0144] 13 C NMR (100MHz, CDCl3) δ162.6,137.5,127.0,114.4,72.5,55.7,24.1,23.9ppm.

[0145] HRMS(ESI,m / z):calculated for C 10 H 14 O3SNa + [M+Na] + :237.0556,found:267.0664.

[0146] [α] 25 D = +81.2 (c = 0.9 in CHCl3).

[0147] HPLC analysis: 97:3e.r. (Chiralcel IA, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (minor) = 9.3min, Rt (major) = 10.3min.

[0148] (R)-2-(trifluoromethoxy)-benzenesulfinic acid isopropyl ester (4m)

[0149] Substituent R 1 It is 2-trifluoromethoxyphenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0150] Colorless oil (18.5 mg, 69% yield).

[0151] 1 H NMR(400MHz, CDCl3)δ8.01(dd,J=7.7,1.8Hz,1H),7.58(m,1H),7.49(td,J=7.6,1.1Hz, 1H),7.36-7.30(m,1H),4.90-4.34(m,1H),1.39(d,J=6.2Hz,3H),1.31(d,J=6.3Hz,3H).

[0152] 13 C NMR (100MHz, CDCl3) δ146.5,137.9,133.6,127.3,126.0,119.9,74.5,23.8,23.42ppm.

[0153] 19 F NMR (376MHz, CDCl3) δ-57.04ppm.

[0154] HRMS(ESI,m / z):calculated for C 10 H 11 F3O3SNa + [M+Na] + :291.0273,found:291.0274.

[0155] [α] 25 D = +19.4 (c = 0.4 in CHCl3).

[0156] HPLC analysis: 98:2e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 5.9min, Rt (minor) = 5.4min.

[0157] (R)-2,5-Dimethoxybenzenesulfinic acid isopropyl ester (4n)

[0158] Substituent R 1 It is 2,5-dimethoxyphenyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0159] Pale yellow oil (21.0 mg, 86% yield).

[0160] 1 H NMR (400MHz, CDCl3) δ7.43(d,J=3.1Hz,1H),7.02(dd,J=8.9,3.2Hz,1H),6.89(d,J=8.9Hz,1H ),4.75-4.52(m,1H),3.86(s,3H),3.83(s,3H),1.36(d,J=6.2Hz,3H),1.26(d,J=6.3Hz,3H).

[0161] 13 C NMR (100MHz, CDCl3) δ154.0,151.2,133.6,120.0,112.9,109.0,73.3,56.3,56.0,23.7,23.7ppm.

[0162] HRMS(ESI,m / z):calculated for C 11 H 16 O4SNa + [M+Na] + :267.0662,found:267.0664.

[0163] [α] 25 D = +22.2 (c = 0.6 in CHCl3).

[0164] HPLC analysis: 95:5e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 11.6min, Rt (minor) = 10.0min.

[0165] (R)-4-Nitrobenzenesulfinic acid isopropyl ester (4o)

[0166] Substituent R 1 It is 4-nitro, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at room temperature;

[0167] Pale yellow oil (11.7 mg, 51% yield).

[0168] 1H NMR (400MHz, CDCl3) δ8.38(d,J=8.8Hz,2H),7.90(d,J=8.8Hz,2H),4.76-4.54(m,1H),1.43(d,J=6.2Hz,3H),1.31(d,J=6.3Hz,3H).

[0169] 13 C NMR (100MHz, CDCl3) δ152.1,150.1,126.7,124.3,74.7,24.0,23.9ppm.

[0170] HRMS(ESI,m / z):calculated for C9H 11 NO4SNa + [M+Na] + :252.0301,found:252.0302.

[0171] [α] 25 D = +44.5 (c = 0.4 in CHCl3).

[0172] HPLC analysis: 92:8e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 15.8min, Rt (minor) = 16.9min.

[0173] (R)-2-naphthalene-sulfinic acid isopropyl ester (4p)

[0174] Substituent R 1 It is naphthyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0175] Colorless oil (14.8 mg, 63% yield).

[0176] 1 H NMR (400MHz, CDCl3) δ8.37-8.23(m,1H),8.07-7.96(m,2H),7.94-7.87(m,1H),7.70(dd,J=8.6, 1.8Hz,1H),7.64-7.52(m,2H),4.72-4.59(m,1H),1.42(d,J=6.2Hz,3H),1.26(d,J=6.3Hz,3H).

[0177] 13C NMR (100MHz, CDCl3) δ142.8,135.0,132.7,129.3,129.2,128.3,128.1,127.3,126.0,73.1,24.2,23.9ppm.

[0178] HRMS(ESI,m / z):calculated for C 13 H 14 O2SNa + [M+Na] + :257.0607,found:257.0609.

[0179] [α] 25 D = +21.6 (c = 0.4 in CHCl3).

[0180] HPLC analysis: 98:2e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 17.4min, Rt (minor) = 23.0min.

[0181] (R)-1-Naphthylsulfinate isopropyl ester (4q)

[0182] Substituent R 1 It is naphthyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1;

[0183] Colorless oil (17.3 mg, 74% yield).

[0184] 1 H NMR (400MHz, CDCl3) δ8.36-8.25(m,1H),8.19(dd,J=7.2,1.3Hz,1H),8.03(dt,J=8.3,1.1Hz,1H),7. 97-7.89(m,1H),7.73-7.49(m,3H),4.78-4.58(m,1H),1.40(d,J=6.3Hz,3H),1.09(d,J=6.3Hz,3H).

[0185] 13 C NMR (100MHz, CDCl3) δ140.3,133.9,132.8,129.5,128.9,127.5,126.8,125.1,123.9,122.7,72.6,24.2,23.7ppm.

[0186] HRMS(ESI,m / z):calculated for C 13 H 14 O2SNa + [M+Na] + :257.0607,found:257.0609.

[0187] [α] 25 D = +10.4 (c = 0.2 in CHCl3).

[0188] HPLC analysis: 97:3e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 15.8min, Rt (minor) = 16.7min.

[0189] (R)-Isopropyl cyclohexanesulfinate (4r)

[0190] Substituent R 1 It is a cyclohexyl group, R 2 The product is isopropyl, and the preparation method and conditions are the same as in Example 1, using toluene as the solvent;

[0191] Colorless oil (8.6 mg, 45% yield).

[0192] 1 H NMR(400MHz, CDCl3)δ4.45(m,1H),2.49(tt,J=11.4,3.7Hz,1H),2.10-1.94(m,2H),1.90-1.80(m,2H),1.73-1.6 1(m,1H),1.44-1.37(m,1H),1.35(d,J=6.3Hz,3H),1.33-1.30(m,1H),1.29(d,J=6.3Hz,3H),1.26-1.23(m,3H).

[0193] 13 C NMR (100MHz, CDCl3) δ74.1,63.9,25.8,25.3,25.2,24.6,24.5,24.0,23.2ppm.

[0194] HRMS(ESI,m / z):calculated for C9H 18 O2SNa + [M+Na] + :213.0920,found:213.0920.

[0195] [α] 25 D = +47.3 (c = 0.6 in CHCl3).

[0196] HPLC analysis: 99:1e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (minor) = 17.6min, Rt (major) = 19.2min.

[0197] (R)-Isopropyl butyl sulfinate (4s)

[0198] Substituent R 1 For butyl, R 2 The product is isopropyl, and the preparation method and conditions are the same as in Example 1, using toluene as the solvent;

[0199] Colorless oil (8.2 mg, 50% yield).

[0200] 1 H NMR (400MHz, CDCl3) δ4.61-4.32(m,1H),2.93-2.43(m,2H),1.75-1.60(m,2H),1.5 1-1.39(m,2H),1.37(d,J=6.2Hz,3H),1.31(d,J=6.2Hz,3H),0.95(t,J=7.3Hz,3H).

[0201] 13 C NMR (100MHz, CDCl3) δ74.0,57.5,24.0,23.6,23.3,22.1,13.9ppm.

[0202] HRMS(ESI,m / z):calculated for C7H 16 O2SNa + [M+Na] + :187.0763,found:2187.0760.

[0203] [α] 25 D = +19.4 (c = 0.4 in CHCl3).

[0204] HPLC analysis: 91:9e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 0.8mL / min), Rt(major)=16.3min, Rt(minor)=17.4min.

[0205] (R)-Thiophene-2-sulfinyl propyl ester (4t)

[0206] Substituent R 1 It is a thiophene group, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at 35°C;

[0207] Colorless oil (16 mg, 84% yield).

[0208] 1 H NMR (400MHz, CDCl3) δ7.62 (dd, J=5.0, 1.3Hz, 1H), 7.49 (dd, J=3.8, 1.3Hz, 1H), 7.14 (d d,J=4.9,3.7Hz,1H),4.78-4.61(m,1H),1.40(d,J=6.2Hz,3H),1.29(d,J=6.3Hz,3H).

[0209] 13 C NMR (100MHz, CDCl3) δ148.9,131.4,129.6,127.7,73.0,24.2,23.9ppm.

[0210] HRMS(ESI,m / z):calculated for C7H 10 O2S2Na + [M+Na] + :213.0014,found:213.0015.

[0211] [α] 25 D = +21.6 (c = 0.7 in CHCl3).

[0212] HPLC analysis: 97:3e.r. (Chiralcel IC, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 16.8min, Rt (minor) = 17.4min.

[0213] (R)-5-chlorothiophene-2-sulfinic acid isopropyl ester (4u)

[0214] Substituent R 1 It is 5-chlorothiophene group, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at 35°C;

[0215] Colorless oil (15.1 mg, 67% yield).

[0216] 1 H NMR (400MHz, CDCl3) δ7.26 (d, J = 3.8Hz, 1H), 6.96 (d, J = 3.9Hz, 1H), 4.80-4.61 (m, 1H), 1.39 (d, J = 6.2Hz, 3H), 1.32 (d, J = 6.3Hz, 3H).

[0217] 13 C NMR (100MHz, CDCl3) δ146.9,136.9,129.1,127.1,73.5,24.2,23.9ppm.

[0218] HRMS(ESI,m / z):calculated for C7H9ClO2S2Na + [M+Na] + :246.9625,found:246.9627.

[0219] [α] 25 D = +51.9 (c = 0.7 in CHCl3).

[0220] HPLC analysis: 94:6e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=10.5min, Rt(minor)=11.7min.

[0221] (R)-5-bromothiophene-2-sulfinic acid isopropyl ester (4v)

[0222] Substituent R 1 It is 5-bromothiophene, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at 35°C;

[0223] Colorless oil (20.2 mg, 75% yield).

[0224] 1 H NMR (400MHz, CDCl3) δ7.23(d,J=3.9Hz,1H),7.10(d,J=3.9Hz,1H),4.76-4.65(m,1H),1.39(d,J=6.2Hz,3H),1.31(d,J=6.3Hz,3H).

[0225] 13C NMR (100MHz, CDCl3) δ149.7,130.7,129.9,119.4,73.5,24.2,23.9ppm.

[0226] HRMS(ESI,m / z):calculated for C7H9BrO2S2Na + [M+Na] + :290.9120,found:290.9124.

[0227] [α] 25 D = +20.1 (c = 0.5 in CHCl3).

[0228] HPLC analysis: 94:6e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=11.4min, Rt(minor)=12.8min.

[0229] (R)-Quinoline-8-sulfinic acid isopropyl ester (4w)

[0230] Substituent R 1 It is quinolinyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at room temperature;

[0231] Colorless oil (11.8 mg, 50% yield).

[0232] 1 H NMR (400MHz, CDCl3) δ8.99(dd,J=4.3,1.7Hz,1H),8.39(dd,J=7.3,1.4Hz,1H),8.24(dd,J=8.3,1.8Hz,1H),8.01(dd,J=8.3,1 .4Hz,1H),7.74(t,J=7.7Hz,1H),7.51(dd,J=8.4,4.2Hz,1H),4.88-4.76(m,1H),1.38(d,J=6.2Hz,3H),1.25(d,J=6.2Hz,3H).

[0233] 13 C NMR (100MHz, CDCl3) δ150.8,145.1,142.9,136.2,131.9,128.5,126.4,126.3,122.1,74.1,23.9,23.8ppm.

[0234] HRMS(ESI,m / z):calculated for C 12 H 13 NO2SNa + [M+Na] + :258.0559,found:258.0558.

[0235] [α] 25 D = +29.5 (c = 0.2 in CHCl3).

[0236] HPLC analysis: 90:10e.r. (Chiralcel IA, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (minor) = 12.1min, Rt (major) = 13.6min.

[0237] (R)-Isopropyl pyridine-3-sulfinate (4z)

[0238] Substituent R 1 It is pyridinyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at room temperature;

[0239] Colorless oil (10.6 mg, 57% yield).

[0240] 1 H NMR (400MHz, CDCl3) δ8.87(d,J=2.2Hz,1H),8.77(dd,J=4.9,1.6Hz,1H),8.06(ddd,J=7.9,2.3,1.7Hz, 1H),7.48(ddd,J=7.9,4.8,0.9Hz,1H),4.80-4.57(m,1H),1.43(d,J=6.2Hz,3H),1.32(d,J=6.2Hz,3H).

[0241] 13 C NMR (100MHz, CDCl3) δ152.8,147.3,142.2,133.1,124.0,24.0,23.9ppm.

[0242] HRMS(ESI,m / z):calculated for C8H 11 NO2SNa + [M+Na] + :208.0403,found:208.0405.

[0243] [α]25 D = +19.4 (c = 0.4 in CHCl3).

[0244] HPLC analysis: 95:5e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 11.7min, Rt (minor) = 12.5min.

[0245] (R)-5-bromopyridine-3-sulfinic acid isopropyl ester (4y)

[0246] Substituent R 1 It is 5-bromopyridyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at 35°C;

[0247] Colorless oil (18.2 mg, 69% yield).

[0248] 1 H NMR (400MHz, CDCl3) δ8.85-8.73(m,2H),8.18(t,J=2.0Hz,1H),4.67(m,1H),1.43(d,J=6.2Hz,3H),1.34(d,J=6.3Hz,3H).

[0249] 13 C NMR (100MHz, CDCl3) δ153.8,145.1,143.5,135.5,121.4,74.9,23.8ppm.

[0250] HRMS(ESI,m / z):calculated for C8H 10 BrNO2SNa + [M+Na] + :285.9508,found:285.9508.

[0251] [α] 25 D = +21.4 (c = 0.2 in CHCl3).

[0252] HPLC analysis: 91:9e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 6.8min, Rt (minor) = 8.2min.

[0253] (R)-2-methoxypyridine-3-sulfinic acid isopropyl ester (4x)

[0254] Substituent R 1 It is 2-methoxypyridyl, R 2 The compound is isopropyl, and the preparation method and conditions are the same as in Example 1, prepared at 35°C;

[0255] Colorless oil (10.8 mg, 50% yield).

[0256] 1 H NMR (400MHz, CDCl3) δ8.30(dd,J=5.0,1.9Hz,1H),8.15(dd,J=7.4,1.9Hz,1H),7.08(dd,J=7.4,5.0Hz,1H),4.62(m 1H), 4.04 (s, 3H), 1.38 (d, J = 6.2Hz, 3H), 1.29 (d, J = 6.3Hz, 3H).

[0257] 13 C NMR (100MHz, CDCl3) δ160.6,150.6,135.1,128.1,117.3,74.2,53.9,23.8,23.7ppm.

[0258] HRMS(ESI,m / z):calculated for C9H 13 NO3SNa + [M+Na] + :238.0508,found:238.0508.

[0259] [α] 25 D = +14.3 (c = 0.3 in CHCl3).

[0260] HPLC analysis:91:9e.r.(Chiralcel OD-H,5:95 i PrOH / n-Hexane, 0.8mL / min), Rt(minor)=6.3min, Rt(major)=7.4min.

[0261] (R)-4-Methylbenzenesulfinic acid tert-butyl ester (5a)

[0262] Substituent R 1 It is toluene, R 2 The formulation is tert-butyl, and the preparation method and conditions are the same as in Example 1;

[0263] Colorless oil (12.9 mg, 61% yield).

[0264] 1 H NMR (400MHz, CDCl3) δ7.56 (d, J = 8.2Hz, 2H), 7.31 (d, J = 7.6Hz, 2H), 2.41 (s, 3H), 1.55 (s, 6H).

[0265] 13 C NMR (100MHz, CDCl3) δ143.8,142.2,129.8,125.0,82.7,30.1,21.6ppm.

[0266] HRMS(ESI,m / z):calculated for C 11 H 16 O2SNa + [M+Na] + :235.0763,found:235.0764.

[0267] [α] 25 D = +37.4 (c = 0.7 in CHCl3).

[0268] HPLC analysis: 99:1e.r. (Chiralcel IA, 2:98i-PrOH / n-Hexane, 0.5mL / min), Rt (minor) = 19.8, min, Rt (major) = 21.4min.

[0269] (R)-4-methylbenzyl benzyl sulfinate (5b)

[0270] Substituent R 1 It is toluene, R 2 The compound is benzyl, and the preparation method and conditions are the same as in Example 1;

[0271] Colorless oil (18.2 mg, 74% yield).

[0272] 1 H NMR (400MHz, CDCl3) δ7.64-7.46(m,2H),7.37-7.07(m,7H),4.97(d,J=11.4Hz,1H),4.50(d,J=11.4Hz,1H),2.38(s,3H).

[0273] 13C NMR (100MHz, CDCl3) δ143.0,141.7,135.7,129.9,128.7,128.6,125.5,65.7,21.7ppm.

[0274] HRMS(ESI,m / z):calculated for C 14 H 14 O2SNa + [M+Na] + :269.0607,found:269.0608.

[0275] [α] 25 D = +29.6 (c = 0.7 in CHCl3).

[0276] HPLC analysis: 89:11e.r. (Chiralcel IB, 5:95i-PrOH / n-Hexane, 0.8mL / min), Rt (major) = 18.5min, Rt (minor) = 21.1min.

[0277] Cyclobutyl(R)-4-methylbenzenesulfinate (5c)

[0278] Substituent R 1 It is toluene, R 2 The compound was cyclobutyl, and the preparation method and conditions were the same as in Example 1 (colorless oil, 14.1 mg, 67% yield).

[0279] 1 H NMR (400MHz, CDCl3) δ7.59(d,J=8.3Hz,2H),7.32(d,J=7.7Hz,2H),4.70(tt,J=8.1,7.1Hz,1H),2.41(s,3H),2.39 -2.28(m,1H),2.27-2.16(m,1H),2.05(dtdd,J=11.2,10.3,8.0,0.8Hz,1H),1.82-1.62(m,1H),1.58-1.42(m,1H).

[0280] 13 C NMR (100MHz, CDCl3) δ142.7,142.5,129.8,125.2,70.1,32.2,32.1,21.6,13.5ppm.

[0281] HRMS(ESI,m / z):calculated for C 11 H14 O2SNa + [M+Na] + :233.0607,found:233.0607.

[0282] [α] 25 D = +62.5 (c = 0.5 in CHCl3).

[0283] HPLC analysis: 94:6e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=26.9min, Rt(minor)=28.9min.

[0284] Cyclohexyl(R)-4-methylbenzenesulfinate (5d)

[0285] Substituent R 1 It is toluene, R 2 Cyclohexyl was prepared using the same methods and conditions as in Example 1; colorless oil (18.8 mg, 79% yield).

[0286] 1 H NMR(400MHz, CDCl3)δ7.60(d,J=8.2Hz,2H),7.32(d,J=8.0Hz,2H),4.42-4.23(m,1H),2 .42(s,3H),2.10-1.92(m,1H),1.85-1.65(m,2H),1.62-1.42(m,3H),1.41-1.15(m,3H).

[0287] 13 C NMR (100MHz, CDCl3) δ143.0,142.5,129.7,125.2,77.9,33.9,33.8,25.3,24.0,23.9,21.6ppm.

[0288] HRMS(ESI,m / z):calculated for C 13 H 18 O2SNa + [M+Na] + :261.0920,found:261.0922.

[0289] [α] 25 D = +61.7 (c = 0.5 in CHCl3).

[0290] HPLC analysis: 97:3e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=29,6min, Rt(minor)=34.8min.

[0291] Cycloheptayl(R)-4-methylbenzenesulfinate (5e)

[0292] Substituent R 1 It is toluene, R 2 The compound is cycloheptanyl, prepared using the same methods and conditions as in Example 1; colorless oil (17.2 mg, 68% yield).

[0293] 1 H NMR(400MHz, CDCl3) δ7.59(d,J=8.2Hz,2H),7.31(d,J=8.1Hz,2H),4.64-4.39 (m,1H),2.41(s,3H),2.11-1.96(m,1H),1.91-1.79(m,2H),1.73-1.29(m,9H).

[0294] 13 C NMR (100MHz, CDCl3) δ143.0,142.5,129.7,125.2,80.5,36.0,35.8,28.3,28.2,22.7,22.6,21.6ppm.

[0295] HRMS(ESI,m / z):calculated for C 14 H 20 O2SNa + [M+Na] + :275.1076,found:275.1078.

[0296] [α] 25 D = +27.2 (c = 0.3 in CHCl3).

[0297] HPLC analysis: 97:3e.r. (Chiralcel IC, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=29.3min, Rt(minor)=31.9min.

[0298] (1R,3S,5R,7R)-adamantane-2-yl(R)-4-methylbenzenesulfinate (5f)

[0299] Substituent R 1 It is toluene, R 2 The preparation method and conditions are the same as in Example 1, for (1R,3S,5R,7R)-adamantane-2-yl.

[0300] Colorless oil (23.8 mg, 82% yield).

[0301] 1 H NMR (400MHz, CDCl3) δ7.60(d,J=8.2Hz,1H),7.30(d,2H),4.50(t,J=3.6Hz,1H),2.40(s,3H),2.15( d,J=3.6Hz,1H),2.09-1.98(m,2H),1.87(m,2H),1.78(m,4H),1.73-1.65(m,3H),1.59-1.43(m,2H).

[0302] 13 C NMR (100MHz, CDCl3) δ143.2,142.4,129.6,125.1,82.1,37.4,36.7,36.6,33.8,33.6,31.4,31.3,27.2,26.9,21.5ppm.

[0303] HRMS(ESI,m / z):calculated for C 17 H 22 O2SNa + [M+Na] + :313.1233,found:313.1230.

[0304] [α] 25 D = +39.7 (c = 0.4 in CHCl3).

[0305] HPLC analysis: 98:2e.r. (Chiralcel IE, 2:98i-PrOH / n-Hexane, 1.0mL / min), Rt (major) = 18.9min, Rt (minor) = 23.5min.

[0306] (S)-1-Methoxypropane-2-yl(R)-4-methylbenzenesulfinate (5g)

[0307] Substituent R 1 It is toluene, R 2 It is methoxypropane-2-yl, and the preparation method and conditions are the same as in Example 1;

[0308] Colorless oil (19.6 mg, 86% yield).

[0309] 1 H NMR (400MHz, CDCl3) δ7.61(d,J=8.2Hz,2H),7.33(d,J=8.5Hz,2H),4.54(dtd,J=11.6,6. 4,5.1Hz,2H),3.45-3.39(m,1H),3.33-3.28(m,4H),2.42(s,3H),1.39(d,J=6.4Hz,3H).

[0310] 13 C NMR (100MHz, CDCl3) δ142.8,142.7,129.7,125.3,75.9,74.2,59.3,21.6,19.0ppm.

[0311] HRMS(ESI,m / z):calculated for:C 11 H 16 O3SNa + [M+Na] + :251.0712,found:251.0708.

[0312] [α] 25 D =+19.2(c=0.3in CHCl3)93:7d.r.(determined by 1 H NMR).

[0313] (R)-Tetrahydrofuran-3-yl(R)-4-methylbenzenesulfinate (5h)

[0314] Substituent R 1 It is toluene, R 2 The tetrahydrofuranyl group was prepared using the same methods and conditions as in Example 1.

[0315] Colorless oil (15.6 mg, 69% yield).

[0316] 1 H NMR(400MHz, CDCl3) δ7.60(d,J=8.2Hz,2H),7.34(d,J=7.9Hz,2H),5.09-4.82(m,1H),3.98 -3.79(m,2H),3.72(q,J=7.0Hz,2H),2.57(s,0H),2.43(s,3H),2.18(td,J=7.7,5.0Hz,2H).

[0317] 13 C NMR (100MHz, CDCl3) δ145.1,133.8,130.0,127.7,81.5,72.7,66.8,33.1,21.6ppm.

[0318] HRMS(ESI,m / z):Calculated for C 11 H 14 O3SNa + [M+Na] + :249.0556,found:249.0558.

[0319] [α] 25 D =+33.4(c=0.5in CHCl3).95:5d.r.(determined by 1 H NMR).

[0320] ((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl(R)-4-methylbenzenesulfinate (5i)

[0321] Substituent R 1 It is toluene, R 2 The preparation method and conditions for (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl are the same as in Example 1;

[0322] White solid (25.3 mg, 86% yield). MPa 100.8-101.4℃;

[0323] 1 H NMR (400MHz, CDCl3) δ7.60 (d, J=8.2Hz, 2H), 7.32 (d, J=7.9Hz, 2H), 4.12 (td, J= 10.8, 4.5Hz, 1H), 2.42 (s, 3H), 2.28 (dq, J=10.4, 3.0, 2.4Hz, 1H), 2.13 (pd, J=7. 0,2.6Hz,1H),1.72-1.63(m,2H),1.52-1.44(m,1H),1.39-1.30(m,1H),1.30-1 .15(m,3H),0.96(d,J=6.5Hz,3H),0.86(d,J=7.1Hz,3H),0.72(d,J=6.9Hz,3H).

[0324] 13C NMR (100MHz, CDCl3) δ143.3,142.5,129.7,125.1,80.2,48.0,43.1,34.1,31.8,25.3,23.3,22.2,21.6,21.0,15.6ppm.

[0325] HRMS(ESI,m / z):calculated for C 17 H 26 O2SNa + [M+Na] + :317.1546,found:317.1548.

[0326] [α] 25 D =+43.3(c=0.3in CHCl3).>20:1d.r.(determined by 1 H NMR).

[0327] (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl(R)-4-methylbenzenesulfinate ((Epi)-5i)

[0328] Substituent R 1 It is toluene, R 2 The preparation method and conditions for (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl are the same as in Example 1;

[0329] White solid (23.9 mg, 81% yield). MPa 99.8-100.9℃;

[0330] 1 H NMR (400MHz, CDCl3) δ7.59(d,J=8.2Hz,2H),7.31(d,J=8.0Hz,2H),4.12(td,J=10 .7,4.5Hz,1H),2.41(s,3H),2.32-2.21(m,1H),2.13(pd,J=7.0,2.6Hz,1H),1.68( dt,J=12.0,2.8Hz,2H),1.48(m,1H),1.39-1.29(m,1H),1.22(q,J=11.8Hz,1H),1 .11-1.00(m,1H),0.96(d,J=6.5Hz,3H),0.93-0.80(m,4H),0.71(d,J=6.9Hz,3H).

[0331] 13C NMR (100MHz, Acetone-d6) δ144.8,143.3,130.4,125.7,80.3,48.8,43.8,34.8,32.3,26.0,23.9,22.3,21.4,21.1,16.0ppm.

[0332] HRMS(ESI,m / z):calculated for C 17 H 26 O2SNa + [M+Na] + :317.1546,found:317.1548.

[0333] [α] 25 D =+66.8(c=0.33in CHCl3).>20:1d.r.(determined by 1 H NMR).

[0334] 2-((R)-4-methylcyclohexyl-3-en-1-yl)propyl-2-yl(R)-4-methylbenzenesulfinate (5j)

[0335] Substituent R 1 It is toluene, R 2 The preparation method and conditions for 2-((R)-4-methylcyclohexyl-3-en-1-yl)propyl-2-yl are the same as in Example 1;

[0336] Colorless oil (18.7 mg, 64% yield).

[0337] 1 H NMR(400MHz, CDCl3)δ7.56(d,J=6.6Hz,2H),7.30(d,J=8.0Hz,2H),5.46-5.25(m,1H),2.41(s,3H) ,2.15-1.78(m,6H),1.63(s,3H),1.55(d,J=4.7Hz,3H),1.51(d,J=7.0Hz,3H),1.35-1.28(m,1H).

[0338] 13 C NMR (100MHz, CDCl3) δ146.9,141.9,134.1,130.4,127.2,120.7,72.9,58.6,45.1,31.1,27.5,27.0,26.4,24.1,23.4,21.9,18.5ppm.

[0339] HRMS(ESI,m / z):calculated for C 17 H 24 O2SNa + [M+Na] + :315.1389,found:315.1385.

[0340] [α] 25 D =+413.3(c=0.3in CHCl3).>20:1d.r.(determined by 1 H NMR).

[0341]

[0342] (3S,5S,8R,10S,13S)-10,13-dimethyl-17-oxohexadecyl-1H-cyclopentyl-3-yl(R)-4-methylbenzenesulfinate

[0343] Substituent R 1 It is toluene, R 2 The preparation method and conditions are the same as in Example 1; (3S,5S,8R,10S,13S)-10,13-dimethyl-17-oxohexadecylhydro-1H-cyclopentyl-3-yl.

[0344] White solid (33.9 mg, 79% yield).

[0345] 1 H NMR (400MHz, CDCl3) δ7.58(d,J=7.6Hz,2H),7.32(d,J=6.0Hz,2H),4.61(dt,J=7.5,2.6Hz,1H),2.52-2.34(m,4H),2.11-1.98(m,1H) ,1.96-1.85(m,1H),1.82-1.67(m,3H),1.67-1.39(m,8H),1.35-1.12(m,7H),1.06-0.90(m,1H),0.84(s,3H),0.78(d,J=5.1Hz,3H).

[0346] 13 C NMR (100MHz, CDCl3) δ221.4,144.5,134.8,129.9,127.7,80.0,54.1,51.5,47.9,39. 3,35.9,35.8,35.0,33.5,32.3,31.6,27.9,26.9,21.8,21.7,20.1,13.9,11.5.ppm.

[0347] HRMS(ESI,m / z):calculated for C 26 H 36 O3SNa + [M+Na] + :451.2277,found:451.2278.

[0348] [α] 25 D =+110.3(c=0.33in CHCl3);>20:1d.r.(determined by 1 H NMR).

[0349]

[0350] 17-Acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecylhydropenten-1H-cyclopentylphenanthrene-3-yl(R)-4-methylbenzenesulfinate (5l)

[0351] Substituent R 1 It is toluene, R 2 The compound is 17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecylhydropenten-1H-cyclopentylphenanthrene-3-yl, and the preparation method and conditions are the same as in Example 1;

[0352] Colorless oil (37.5 mg, 82% yield).

[0353] 1 H NMR (400MHz, CDCl3) δ7.60(d,J=8.2Hz,2H),7.32(d,J=8.2Hz,2H),5.54-5.00(m,1H),4.19(tt,J=11.4,4.9Hz,1H),2.58-2.46(m,2H),2.42(d,J= 2.1Hz,3H),2.26-2.15(m,1H),2.11(s,3H),2.07-1.93(m,2H),1.92-1.5 3(m,8H),1.51-1.39(m,3H),1.29-1.05(m,4H),0.99(s,3H),0.62(s,3H).

[0354] 13C NMR (100MHz, CDCl3) δ209.7,142.9,142.7,139.8,129.8,125.1,122.7,78.9,63.8,56.9,49.9 ,44.1,40.4,40.2,38.9,37.3,36.6,31.9,31.7,29.9,24.6,22.9,21.7,21.2,19.4,13.3ppm.

[0355] HRMS(ESI,m / z):calculated for C 28 H 38 O3SNa + [M+Na] + :477.2434,found:477.2430.

[0356] [α] 25 D =+129.7(c=0.33in CHCl3);>20:1d.r.(determined by 1 H NMR).

[0357] (R)-Butyl benzenesulfinate (4a)

[0358] Substituent R 1 It is a phenyl group, R 2 The butyl group was prepared using the same methods and conditions as in Example 1.

[0359] Colorless oil (12.1 mg, 61% yield).

[0360] 1 H NMR (400MHz, CDCl3) δ7.75-7.63(m,2H),7.55-7.44(m,3H),4.01(dt,J=9.9,6.6Hz,1H), 3.59(dt,J=9.9,6.5Hz,1H),1.66-1.50(m,2H),1.41-1.26(m,2H),0.84(t,J=7.4Hz,3H).

[0361] 13 C NMR (100MHz, CDCl3) δ144.8,132.1,129.1,125.3,64.7,31.7,18.9,13.6ppm.

[0362] HRMS(ESI,m / z):calculated for C 10 H 14 O2SNa +[M+Na] + :221.0607,found:221.0600

[0363] [α] 25 D = +61.13 (c = 0.4 in CHCl3)

[0364] HPLC analysis: 95:5e.r. (Chiralcel AS-H, 5:95i-PrOH / n-Hexane, 1.0mL / min), Rt (major) = 22.9min, Rt (minor) = 21.6min.

[0365] (R)-Ethyl benzenesulfinate (4b)

[0366] Substituent R 1 It is a phenyl group, R 2 The ethyl group was prepared using the same methods and conditions as in Example 1.

[0367] Colorless oil (11.4 mg, 67% yield).

[0368] 1 H NMR (400MHz, CDCl3) δ7.77-7.65(m,2H),7.58-7.46(m,3H),4.20-3.99(m,1H),3.79-3.63(m,1H),1.27(t,J=7.1Hz,3H).

[0369] 13 C NMR (100MHz, CDCl3) δ145.0,132.2,129.1,125.3,61.1,15.7ppm.

[0370] HRMS(ESI,m / z):calculated for C8H 10 O2SNa + [M+Na] + :193.0294,found:193.0290.

[0371] [α] 25 D =(c=0.4in CHCl3)

[0372] HPLC analysis: 95:5e.r. (Chiralcel OD-H, 5:95i-PrOH / n-Hexane, 1.0mL / min), Rt (major) = 8.8min, Rt (minor) = 10.0min.

[0373] Example 2

[0374] Preparation of chiral sulfoxide ester derivatives:

[0375]

[0376] 1. Preparation methods of compounds (S)-10, (S)-11, (S)-12, and (S)-13

[0377] Under nitrogen protection, 19.8 mg (R)-4d was dissolved in 1.0 mL of tetrahydrofuran solution. Then, 0.2 mL of methyl magnesium bromide, 0.12 mL of tert-butyl magnesium bromide, 0.2 mL of phenyl magnesium bromide, or 0.1 mL of isopropenyl magnesium bromide was added at -20 °C or -78 °C. After stirring for 30 minutes, the reaction was quenched with saturated ammonium chloride aqueous solvent, extracted with ethyl acetate, and concentrated under vacuum. The residue was purified by column chromatography on silica gel, with polar petroleum ether:ethyl acetate as eluent in a 5:1 ratio, yielding target compounds (S)-10, (S)-11, (S)-12, and (S)-13 in yields of 92%, 92%, 82%, and 88%, respectively.

[0378] 2. Preparation method of compound (S)-14

[0379]

[0380] Under nitrogen protection, 23.3 mg of 2-methylpyridine was dissolved in 1.0 mL of tetrahydrofuran, and 156.3 μL of n-butyllithium was added dropwise at -30 °C. After maintaining the clear red solution at 0 °C for 30 minutes, it was cooled to -70 °C. A solution of 19.8 mg(R)-4d in tetrahydrofuran was slowly added dropwise. The mixture was stirred at -70 °C for 1 hour, quenched with saturated ammonium chloride aqueous solution, diluted with 10.0 mL of n-hexane, washed with brine, extracted with ethyl acetate, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by column chromatography on silica gel with polar petroleum ether:ethyl acetate = 2:1 to give the target compound (S)-14 in 96% yield and with a corresponding selectivity of 97:3.

[0381] 3. Preparation method of compound (S)-15

[0382]

[0383] Under nitrogen protection, 37.5 mg of (2-bromophenyl)-diphenylphosphine was dissolved in 1.0 mL of tetrahydrofuran solution and cooled to -78 °C. 69.0 μL of n-butyllithium was added dropwise to the reaction solution. After the addition was complete, the temperature was raised to 0 °C. The solution was maintained at 0 °C as a clear red color for 30 minutes, and then 19.8 mg of (S)-4d in toluene solution was slowly added. The mixture was stirred at room temperature for 12 hours, quenched with saturated ammonium chloride, diluted with 10.0 mL of n-hexane, washed with brine, extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by silica gel column chromatography with polar petroleum ether:ethyl acetate as eluent (10:1) to give the target compound (S)-15 in 68% yield and with a corresponding selectivity of 95:5.

[0384] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A method for preparing a chiral sulfoxide ester compound, characterized in that, Includes the following steps: 1) Under a nitrogen atmosphere, quinine, sodium sulfite, 2-methyl-6-nitrobenzoic anhydride, carbonate and chloroform are mixed and stirred to obtain a stirred mixture; The carbonates include rubidium carbonate, sodium carbonate, potassium carbonate, or potassium phosphate; 2) The mixture obtained in step 1) is mixed with an alcohol and stirred to obtain a chiral sulfoxide ester compound; The general structural formula of the chiral sulfoxide ester compounds is shown in formula (1): ； Formula (1) sulfinyl esters Among them, the sulfur atom marked with an asterisk (*) is a chiral sulfur atom; R 1 The following are possible meanings: phenyl, tolyl, ethylphenyl, biphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 2-methoxyphenyl, 2-trifluoromethoxyphenyl, 2,5-dimethoxyphenyl, 4-nitro, naphthyl, cyclohexyl, butyl, thienyl, 5-chlorothienyl, 5-bromothienyl, quinolinyl, pyridyl, or 5-bromopyridyl. R 2 It is isopropyl, tert-butyl, benzyl, cyclobutyl, cyclohexyl, cycloheptyl, (1R,3S,5R,7R)-adamantane-2-yl, methoxypropane-2-yl, tetrahydrofuranyl, (1S,2R,5S)-2-isopropyl-5-methylcyclohexyl, 2-((R)-4-methylcyclohexyl-3-en-1-yl)propyl-2-yl, (3S,5S,8R,10S,13S)-10,13-dimethyl-17-oxohexadecyl-1H-cyclopentyl-3-yl, 17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecylhydropenten-1H-cyclopentylphenanthrene-3-yl, butyl, or ethyl.

2. The preparation method according to claim 1, characterized in that, In step 1), the volume ratio of quinine (molar), sodium sulfite (molar), 2-methyl-6-nitrobenzoic anhydride (molar), carbonate (molar), and chloroform (volume ratio) is 0.02 mmol: 0.1 mmol: 0.11 mmol: 0.11 mmol: 1.5 ml.

3. The preparation method according to claim 1, characterized in that, The stirring conditions in step 1) include: a temperature of 25~30℃ and a time of 1 hour.

4. The preparation method according to claim 1, characterized in that, The molar ratio of alcohol in step 2) to quinine in step 1) is 0.105:0.

02.

5. The preparation method according to claim 2 or 4, characterized in that, The alcohols include one or more of methanol, ethanol, isopropanol, tert-butanol, benzyl alcohol, cyclobutanol, cyclohexanol, cycloheptanol, 2-adamantanol, methoxy-propanol, D / L menthol, terpineol, androgensone and pregnenolone.

6. The preparation method according to claim 1, characterized in that, The stirring conditions in step 2) include: a temperature of -10 to 0°C and a time of 24 to 48 hours.

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