CN114957322B - Chiral sulfur compound and preparation method and application thereof - Google Patents

Chiral sulfur compound and preparation method and application thereof Download PDF

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CN114957322B
CN114957322B CN202110907446.2A CN202110907446A CN114957322B CN 114957322 B CN114957322 B CN 114957322B CN 202110907446 A CN202110907446 A CN 202110907446A CN 114957322 B CN114957322 B CN 114957322B
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chiral
compound
sulfur compound
chiral sulfur
potassium
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CN114957322A (en
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王天利
方思强
刘赞娇
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Sichuan University
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Sichuan University
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    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
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Abstract

The invention discloses a chiral sulfur compound and a preparation method and application thereof, wherein the preparation method comprises the following steps: under the action of chiral quaternary phosphonium salt catalyst, adding the compound A and the compound C into an organic solvent, and then adding alkali to react to obtain the chiral sulfur compound. The invention constructs chiral sulfur (including sulfoxide, imine sulfone and sulfoxide amine derivatives) compound in one step through simple chiral micromolecule asymmetric catalytic reaction, and the synthesis method has good functional group compatibility, easy operation, mild reaction condition, tolerance to water and oxygen, no transition metal residue involved in the reaction process and environmental friendliness. The chiral sulfur (including sulfoxide and sulfoxide amine derivatives) compound provided by the invention has high enantioselectivity and great potential in ligand development and drug screening.

Description

Chiral sulfur compound and preparation method and application thereof
Technical Field
The invention relates to the technical fields of chemical industry and medicine, in particular to a chiral sulfur compound and a preparation method and application thereof.
Background
In asymmetric catalysis, chiral sulfur compounds are used as a powerful chiral auxiliary for many asymmetric reactions, exhibiting good chiral induction, e.g., in carbon-carbon bond formation reactions, including 1, 4-addition and cycloaddition. To date, there is no approved chiral sulfur-containing drug in the market. Whereas chiral sulphur compounds evaluated in clinical trials included BAY 1143572, BAY 1251152 and AZD 6738. The time for the long-term neglected development of chiral sulfur compounds in the medical field has mainly been three: lack of commercial availability, limited synthetic methods, and little is known to pharmaceutical chemists about the nature of such compounds. In the last decade, as synthetic methods of chiral sulfur compounds continue to emerge, including flow chemistry and metal catalysis, there has been increasing interest in the investigation of chiral sulfur structures. However, asymmetric catalytic synthesis of chiral sulfur compounds has been a research difficulty and challenge in organic chemistry due to their unique structure. Although there are studies reported at present, most of them are made of metals, particularly transition metals. These methods have quite obvious disadvantages: 1) The reaction conditions are severe and generally require operation in an anhydrous and anaerobic environment; 2) Often with metal residue problems; 3) The reaction has low substituent compatibility for the substrate; therefore, a high-efficiency asymmetric catalysis method is developed to quickly construct chiral sulfur skeleton molecules, and research significance and value of the chiral sulfur skeleton molecules in asymmetric catalysis and pharmacological activity are very important.
Disclosure of Invention
In order to solve the above-mentioned shortcomings in the prior art, the present invention aims to provide a chiral sulfur compound and a preparation method thereof, wherein the chiral sulfur compound comprises a structural general formula I and a corresponding enantiomer or diastereomer thereof, or a salt thereof, or a crystal form thereof:
wherein R is 1 Is that
R 2 Is hydrogen, halogen, C 1-20 Alkyl, benzyl or substituted benzyl, sulfonyl or substituted sulfonyl, phosphoryl or substituted phosphoryl, carbonyl or substituted carbonyl, keto or substituted keto, aryl or substituted aryl;
R 3 is hydrogen, halogen, C 1-20 Alkyl, sulfonyl or substituted sulfonyl, phosphoryl or substituted phosphoryl, carbonyl or substituted carbonyl, keto or substituted keto, aryl or substituted aryl;
x is C 1-20 Alkyl, heteroatom;
Ar 1 is aryl or substituted aryl;
Ar 2 is aryl or substituted aryl.
Further, R 2 Is hydrogen, sulfonyl or substituted sulfonyl, phosphoryl or substituted phosphoryl, keto or substituted keto;
R 3 is hydrogen, sulfonyl or substituted sulfonyl, phenyl or substituted phenyl;
x is a heteroatom (e.g., O, N);
Ar 1 phenyl, phenol or substituted phenol, pyridyl or substituted pyridyl, anilino or substituted anilino, indolyl or substituted indolyl;
Ar 2 is phenyl or substituted phenyl (such as methyl, ethyl, isopropyl, tertiary butyl, benzoyl, halogen, aldehyde group, five-membered ring substitution, heterocyclic substitution, naphthyl substitution), pyridyl, indolyl, quinolyl and pyrrolyl.
Further, the chiral sulfur compound has a specific structural formula:
the preparation method of the chiral sulfur compound comprises the following steps:
under the action of chiral quaternary phosphonium salt catalyst, adding the compound A and the compound C into an organic solvent, then adding alkali, and reacting to obtain the chiral sulfur compound, wherein the synthetic route is as follows:
wherein R is 1 Is thatLG is H or halogen or ester group.
Further, the chiral quaternary phosphonium salt catalyst is:
wherein in compound II, R 1 Is C 1-20 Alkyl, heteroatom-containing alkyl or substituted alkyl; r is R 2 Is carbonyl or substituted carbonyl, keto or substituted keto, ts, thiourea or substituted thiourea; r is R 3 Methyl, benzyl or substituted benzyl; x is Br, I.
Further, the chiral quaternary phosphonium salt catalyst is
Further, the preparation method of the chiral quaternary phosphonium salt catalyst II comprises the following steps:
through wittig reaction, the quaternary phosphonium salt phase transfer catalyst can be prepared through chiral phosphinous in one step, and the synthetic route is as follows:
at room temperature, dissolving chiral phosphinous into acetone, adding iodinated alkane or iodinated aryl compound, stirring overnight, and directly concentrating solvent to obtain the product; or adding benzyl bromide, refluxing xylene for 12 hours, cooling to room temperature, spin-drying, and recrystallizing to obtain a product;
wherein in compound II, R 1 Is C 1-20 Alkyl, heteroatom-containing alkyl or substituted alkyl; r is R 2 Is carbonyl or substituted carbonyl, keto or substituted keto, ts, thiourea or substituted thiourea; r is R 3 Methyl, benzyl or substituted benzyl; x is Br, I.
The preparation process of the trivalent phosphine is carried out by adopting the prior art.
Further, the organic solvent is carbon tetrachloride dichloromethane, N, N-dimethylformamide, chloroform, acetonitrile, 1, 2-dichloroethane, cyclohexane, N-hexane, N-heptane, petroleum ether, hexafluoroisopropanol, trifluoroethanol, methanol, ethanol, dimethyl sulfoxide, tetrahydrofuran, diethyl ether, anisole, methyl tert-butyl ether, ethyl acetate, methyl acetate, toluene, chlorobenzene, xylene or m-trimethylbenzene.
Further, the base is an organic base or an inorganic base, specifically N, N-diisopropylethylamine, triethylamine, DBU, DABCO, potassium tert-butoxide, N-butyllithium, sodium carbonate, sodium bicarbonate, lithium carbonate, potassium dihydrogen phosphate, dipotassium hydrogen phosphate, potassium carbonate, potassium hydrogen carbonate, potassium phosphate trihydrate, sodium hydroxide, lithium hydroxide, potassium hydroxide, cesium hydroxide, sodium hydrogen is potassium phosphate heptahydrate.
Further, the reaction temperature is between-78 and 60 ℃ and the reaction time is between 1 and 80 hours.
The application of the chiral sulfur compound in asymmetric catalytic reaction.
The invention has the following beneficial effects:
(1) The invention constructs chiral sulfur (including sulfoxide, imine sulfone and sulfoxide amine derivatives) compound in one step through simple chiral micromolecule asymmetric catalytic reaction, and the synthesis method has good functional group compatibility, easy operation, mild reaction condition, tolerance to water and oxygen, no transition metal residue involved in the reaction process and environmental friendliness.
(2) The catalyst used in the reaction process is a chiral amino acid derived quaternary phosphonium salt catalyst, the catalyst belongs to a phase transfer catalyst, the reaction process is not limited to an anhydrous and anaerobic environment, and the synthesis steps are simple.
(3) The chiral sulfur (including sulfoxide and sulfoxide amine derivatives) compound provided by the invention has high enantioselectivity (ee is up to 99.5%), and has great potential in ligand development and drug screening.
Drawings
FIG. 1 is a single crystal structure of Compound I-19 in example 4.
FIG. 2 is a HPLC chromatogram of the racemate of Compound I-4 in example 1.
FIG. 3 is a HPLC chart of chiral product of compound I-4 of example 1.
FIG. 4 is a HPLC chromatogram of the racemate of Compound I-5 in example 2.
FIG. 5 is a HPLC chart of chiral product of compound I-5 of example 2.
FIG. 6 is a HPLC chromatogram of the racemate of compound I-6 in example 3.
FIG. 7 is a HPLC chart of chiral product of compound I-6 of example 3.
FIG. 8 is a HPLC chromatogram of the racemate of compound I-19 in example 4.
FIG. 9 is a chiral product HPLC chromatogram of compound I-19 in example 4.
FIG. 10 is a HPLC chromatogram of the racemate of compound I-24 in example 5.
FIG. 11 is a chiral product HPLC chromatogram of compound I-24 in example 5.
FIG. 12 is a HPLC chromatogram of the racemate of compound I-45 of example 6.
FIG. 13 is a chiral product HPLC chromatogram of compound I-45 of example 6.
FIG. 14 is a HPLC chromatogram of the racemate of compound I-51 of example 7.
FIG. 15 is a chiral product HPLC chromatogram of compound I-51 of example 7.
FIG. 16 is a HPLC chromatogram of the racemate of compound I-68 of example 8.
FIG. 17 is a chiral product HPLC chromatogram of compound I-68 of example 8.
FIG. 18 is a HPLC chromatogram of the racemate of compound I-69 of example 9.
FIG. 19 is a chiral product HPLC chromatogram of compound I-69 in example 9.
FIG. 20 is a HPLC chromatogram of the racemate of compound I-70 in example 10.
FIG. 21 is a chiral product HPLC profile of Compound I-70 of example 10.
Detailed Description
The examples given below are only intended to illustrate the invention and are not intended to limit the scope thereof. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1:
preparation of 2- (2-hydroxybenzenesulfoamino) phenyl-bis (4-tert-butylphenyl) phosphinate (I-4):
24.9mg of Compound 1a (0.1 mmol) and 37.7mg of Compound 2a (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 48.0mg of product I-4.
Characterization data: 85% yield, colorless oil; 1 H NMR(400MHz,CDCl 3 )δ7.90(d,J＝88.4Hz,1H),7.86(d,J＝8.4Hz,1H),7.80(d,J＝8.4Hz,1H),7.77(d,J＝8.4Hz,1H),7.73(d,J＝7.8Hz,1H),7.66(d,J＝8.4Hz,1H),7.52(d,J＝3.5Hz,1H),7.49(d,J＝3.5Hz,1H),7.48-7.43(m,3H),7.40-7.32(m,2H),7.10(t,J＝7.8Hz,1H),6.85(d,J＝8.4Hz,1H),6.72-6.64(m,1H),1.32(s,9H),1.31(s,9H). 13 C NMR(100MHz,CDCl 3 )δ157.39,156.64(d,J＝2.9Hz),156.52(d,J＝2.9Hz),149.36(d,J＝7.4Hz),135.36(d,J＝87.3Hz),133.69,132.06(d,J＝8.4Hz),131.95(d,J＝8.4Hz),129.21(d,J＝37.1Hz),127.28(d,J＝16.2Hz),125.96(d,J＝4.2Hz),125.82(d,J＝4.2Hz),123.91,121.54(d,J＝5.0Hz),119.77,119.22(d,J＝8.6Hz),35.23(d,J＝3.2Hz),31.17(d,J＝1.9Hz). 31 P NMR(162MHz,CDCl 3 )δ34.96；
HRMS(ESI)m/z calcd for C 32 H 36 NO 4 PS[M+H] + ＝562.2181,found＝562.2187；
The ee value was 96％,t R (minor)＝24.8min,t R (major)＝37.3min(Chiralcel OD-H,λ＝254nm,10％i-PrOH/hexane,flow rate＝0.5mL/min)；
from the above nuclear magnetism and mass spectrum data, the obtained product had the correct structure.
Example 2
2- (2-hydroxyphenylsulphoxylamine) phenyl-bis (4-biphenylyl) phosphinate (I-5):
36.2mg of Compound 1a (0.1 mmol) and 42.5mg of Compound 2b (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 50.0mg of product I-5.
Characterization data: 83% yield, colorless oil; 1 H NMR(400MHz,CDCl 3 )δ8.06(d,J＝8.2Hz,1H),8.06(d,J＝8.2Hz,1H),8.03(d,J＝8.2Hz,1H),7.95(d,J＝8.2Hz,1H),7.92(d,J＝8.2Hz,1H),7.85(d,J＝7.8Hz,1H),7.76-7.65(m,5H),7.65-7.56(m,4H),7.47(m,5H),7.44-7.33(m,4H),7.15(t,J＝7.6Hz,1H),6.92(d,J＝8.4Hz,1H),6.73(t,J＝7.6Hz,1H). 13 C NMR(100MHz,CDCl 3 )δ157.41,149.31(d,J＝7.2Hz),145.91(d,J＝3.0Hz),145.85(d,J＝3.0Hz),139.75,135.61(d,J＝73.3Hz),132.73(d,J＝2.0Hz),132.61(d,J＝1.8Hz),129.41(d,J＝29.5Hz),129.13,128.80(d,J＝25.4Hz),128.51,127.66(d,J＝5.8Hz),127.52(d,J＝5.8Hz),127.42(d,J＝2.0Hz),127.29,124.26,121.56(d,J＝4.9Hz),119.74,119.35(d,J＝11.8Hz). 31 P NMR(162MHz,CDCl 3 )δ34.41；
HRMS(ESI)m/z calcd for C 72 H 58 N 2 O 8 P 2 S 2 [M+H] + ＝602.1555,found＝602.1555；
The ee value was 90％,t R (major)＝25.2min,t R (minor)＝32.0min(Chiralcel AD-H,λ＝254nm,40％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetic and mass spectrum data, the single crystal structure was found to be correct.
Example 3
Preparation of 2- (2-hydroxyphenylsulfoximine) phenyl-bis (4-methoxyphenyl) phosphinate (I-6):
24.9mg of Compound 1a (0.1 mmol) and 26.2mg of Compound 2c (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 41.0mg of product I-6.
Characterization data: 80% yield, colorless oil; 1 H NMR(400MHz,CDCl 3 )δ7.86(d,J＝8.8Hz,1H),7.83(d,J＝8.8Hz,1H),7.72(m,3H),7.62(d,J＝8.4Hz,1H),7.46(dd,J＝8.2,1.6Hz,1H),7.38(ddd,J＝8.8,7.4,1.6Hz,1H),7.35-7.28(m,1H),7.09(t,J＝7.4Hz,1H),6.98(d,J＝3.0Hz,1H),6.96(d,J＝3.0Hz,1H),6.92(d,J＝3.0Hz,1H),6.90(d,J＝3.0Hz,1H),6.85(dd,J＝8.4,0.8Hz,1H),6.77-6.70(m,1H),3.82(s,3H),3.80(s,3H). 13 C NMR(100MHz,CDCl 3 )δ163.27(d,J＝3.0Hz),163.20(d,J＝3.0Hz),157.44,149.33(d,J＝7.3Hz),135.27(d,J＝90.9Hz),134.12(d,J＝3.0Hz),133.99(d,J＝2.9Hz),129.21(d,J＝29.9Hz),123.90,121.84(d,J＝28.3Hz),121.55(d,J＝5.0Hz),120.38(d,J＝27.5Hz),119.89,119.24(d,J＝11.9Hz),114.44(d,J＝4.8Hz),114.29(d,J＝5.0Hz),55.47(d,J＝2.7Hz). 31 P NMR(162MHz,CDCl 3 )δ35.28；
HRMS(ESI)m/z calcd for C 26 H 24 NO 6 PS[M+H] + ＝510.1140,found＝510.1129；
The ee value was 97％,t R (major)＝28.5min,t R (minor)＝33.8min(Chiralcel AD-H,λ＝254nm,40％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetism and mass spectrum data, the obtained product had the correct structure.
Example 4
Preparation of 4-tert-butyl-2- (5-tert-butyl-2-hydroxybenzenesulfamido) phenyl-diphenyl-phosphinate (I-19):
36.2mg of Compound 1b (0.1 mmol) and 20.2mg of Compound 2d (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 47.0mg of product I-19.
Characterization data: 84% yield, white solid, melting point: 179-181 ℃; 1 H NMR(400MHz,CDCCl3l 3 )δ8.07(d,J＝7.2Hz,1H),8.04(d,J＝7.2Hz,1H),7.91(d,J＝7.3Hz,1H),7.88(d,J＝7.3Hz,1H),7.62(d,J＝1.4Hz,1H),7.58(d,J＝2.4Hz,1H),7.56-7.40(m,8H),7.32(dd,J＝8.6,2.1Hz,1H),6.84(d,J＝8.6Hz,1H),1.18(s,9H),1.11(s,9H). 13 C NMR(100MHz,CDCl 3 )δ155.25,147.54,146.42(d,J＝7.7Hz),142.57,133.93(d,J＝6.9Hz),133.39,132.95(dd,J＝15.3,2.8Hz),132.29(d,J＝10.9Hz),132.03(d,J＝10.8Hz),131.45,130.83(d,J＝8.2Hz),129.46(d,J＝8.9Hz),128.91(dd,J＝13.8,1.7Hz),125.55(d,J＝69.3Hz),121.18(d,J＝4.7Hz),118.79(d,J＝10.3Hz),34.44(d,J＝46.3Hz),31.14(d,J＝4.2Hz). 31 P NMR(162MHz,CDCl 3 )δ33.30；
HRMS(ESI)m/z calcd for C 32 H 36 NO 4 PS[M+H] + ＝562.2181,found＝562.21865；
The ee value was 98％,t R (major)＝9.2min,t R (minor)＝12.5min(Chiralcel OD-H,λ＝254nm,10％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetic and mass spectrum data, the single crystal structure was found to be correct.
Example 5
Preparation of 6- (6 hydroxy-2, 3-2-hydro-1-hydroindenyl-5-phenylsulfoxylamino) -2, 3-2-hydro-5-1-hydroindenyl-diphenyl-phosphinate (I-24):
32.9mg of Compound 1c (0.1 mmol) and 20.2mg of Compound 2d (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 45.0mg of product I-24.
Characterization data: 86% yield, yellow solid, melting point: 112-114 ℃; 1 H NMR(400MHz,CDCCl3l 3 )δ8.05-7.97(m,2H),7.92-7.83(m,2H),7.64(s,1H),7.58-7.53(m,2H),7.52-7.45(m,3H),7.44-7.38(m,2H),7.28(s,1H),6.64(s,1H),2.82-2.74(m,6H),2.61-2.45(m,2H),2.035-1.929(m,4H). 13 C NMR(100MHz,CDCl 3 )δ155.89,152.71(d,J＝100.8Hz),147.91(d,J＝7.4Hz),139.90,135.04,132.87(d,J＝2.8Hz),132.79(d,J＝2.8Hz),132.17(d,J＝10.9Hz),131.98(d,J＝7.2Hz),130.71(d,J＝23.8Hz),129.34(d,J＝21.9Hz),128.74(dd,J＝13.8,1.3Hz),124.23(d,J＝53.5Hz),118.08,117.15(d,J＝4.9Hz),114.42,33.32,33.30,32.13,31.63,25.58,25.45. 31 P NMR(162MHz,CDCl 3 )δ33.14；
HRMS(ESI)m/z calcd for C 30 H 28 NO 4 PS[M+H] + ＝530.1555,found＝530.1555；
The ee value was 90％,t R (major)＝13.0min,t R (minor)＝20.0min(Chiralcel OD-H,λ＝254nm,20％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetic and mass spectrum data, the single crystal structure was found to be correct.
Example 6
Preparation of 2- (2-hydroxybenzenesulfoamino) phenyl-4-tolyl-sulfonate (I-45):
24.9mg of Compound 1a (0.1 mmol) and 22.9mg of Compound 2e (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 33.0mg of product I-45.
Characterization data: 83% yield, yellow solid, melting point: 89-91 ℃; 1 H NMR(400MHz,CDCl 3 )δ12.21(s,1H),7.98(dd,J＝7.9,1.5Hz,1H),7.85(d,J＝8.4Hz,2H),7.56-7.48(m,2H),7.44-7.34(m,5H),6.89(dd,J＝8.4,0.9Hz,1H),6.85-6.77(m,1H),3.58(s,1H),2.48(s,3H). 13 C NMR(100MHz,CDCl 3 )δ157.74,146.96,146.30,136.82,135.84,134.66,132.66,130.05,129.95,129.46,128.92,126.74,122.79,120.04,119.43,119.34,21.97；
HRMS(ESI)m/z calcd for C 19 H 17 NO 5 S 2 [M+H] + ＝404.0626,found＝404.0620；
The ee value was 99.5％,t R (minor)＝20.7min,t R (major)＝25.8min(Chiralcel AD-H,λ＝254nm,30％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetism and mass spectrum data, the obtained product had the correct structure.
Example 7
Preparation of 2- (2-hydroxyphenylsulphoxylamine) phenyl-4-ethyl-sulphonate (I-51):
24.9mg of Compound 1a (0.1 mmol) and 15.4mg of Compound 2f (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, after which concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 28.0mg of product I-51.
Characterization data: 81% yield, colorless oil; 1 H NMR(400MHz,CDCl 3 )δ12.88(s,1H),8.08(dd,J＝8.0,1.7Hz,1H),7.66(dd,J＝8.3,1.2Hz,1H),7.63-7.57(m,1H),7.47-7.38(m,3H),6.98(dd,J＝8.9,1.2Hz,1H),6.91-6.85(m,1H),4.12(s,1H),3.61-3.42(m,2H),1.50(t,J＝7.4Hz,3H). 13 C NMR(100MHz,CDCl 3 )δ157.69,146.15,136.30,136.01,135.02,130.15,129.42,126.77,123.47,120.08,119.86,119.30,47.17,8.17；
HRMS(ESI)m/z calcd for C 14 H 15 NO 5 S 2 [M+H] + ＝342.0470,found＝342.0455；
The ee value was 92％,t R (minor)＝16.9min,t R (major)＝28.0min(Chiralcel IE,λ＝254nm,30％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetism and mass spectrum data, the obtained product had the correct structure.
Example 8
Preparation of 4-tert-butyl-2- (5-tert-butyl-2-hydroxybenzenesulfoamino) phenyl-4-tolyl-sulfonate (I-68):
36.2mg of Compound 1b (0.1 mmol) and 22.9mg of Compound 2e (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 43.0mg of product I-68.
Characterization data: 82% yield, white powder, melting point: 68-70 ℃; 1 H NMR(400MHz,CDCl 3 )δ12.00(s,1H),7.94(s,1H),7.92(s,1H),7.86(d,J＝2.5Hz,1H),7.52-7.47(m,2H),7.43(dd,J＝8.7,2.5Hz,1H),7.39(s,1H),7.37(s,1H),7.35(d,J＝8.6Hz,1H),6.85(d,J＝8.7Hz,1H),3.84(s,1H),2.48(s,3H),1.28(s,9H),1.17(s,9H). 13 C NMR(100MHz,CDCl 3 )δ155.24,150.50,146.14,144.15,142.49,136.72,133.43,132.89,131.23,130.06,128.95,126.76,125.49,122.79,119.14,118.78,35.04,34.27,31.20,21.95；
HRMS(ESI)m/z calcd for C 27 H 33 NO 5 S 2 [M+H] + ＝516.1878,found＝516.1835；
The ee value was 98％,t R (major)＝16.5min,t R (minor)＝18.1min(Chiralcel Ie,λ＝254nm,30％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetism and mass spectrum data, the obtained product had the correct structure.
Example 9
Preparation of 4-phenyl-2- (5-phenyl-2-hydroxybenzenesulfoamino) phenyl-4-tolyl-sulfonate (I-69):
40.2mg of Compound 1d (0.1 mmol) and 22.9mg of Compound 2e (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 45.0mg of product I-69.
Characterization data: 82% yield, white powder, melting point: 123-125 ℃; 1 H NMR(400MHz,CDCl 3 )δ12.32(s,1H),8.28(d,J＝2.4Hz,1H),7.88(d,J＝8.4Hz,2H),7.73(dd,J＝8.6,2.4Hz,1H),7.69(d,J＝2.4Hz,1H),7.65(dd,J＝8.6,2.4Hz,1H),7.59-7.53(m,3H),7.49-7.45(m,2H),7.43-7.39(m,3H),7.38-7.34(m,4H),7.31-7.26(m,1H),7.00(d,J＝8.6Hz,1H),3.85(s,1H),2.47(s,3H). 13 C NMR(100MHz,CDCl 3 )δ157.08,146.30,146.12,140.14,139.29,138.25,136.90,134.65,132.98,132.85,132.63,130.09,129.28,128.96,128.63,128.38,127.40,127.37,127.25,126.68,123.19,120.36,119.88,21.98；
HRMS(ESI)m/z calcd for C 31 H 25 NO 5 S 2 [M+H] + ＝556.1252,found＝556.1252；
The ee value was 98％,t R (major)＝17.0min,t R (minor)＝36.1min(Chiralcel OD-H,λ＝254nm,30％i-PrOH/hexane,flow rate＝1.0mL/min)；
example 10
Preparation of 6- (6 hydroxy-2, 3-2-hydro-1-hydroindenyl-5-phenylsulfoxylamino) -2, 3-2-hydro-5-1-hydroindenyl-4-tolyl-sulfonate (I-70):
32.9mg of Compound 1c (0.1 mmol) and 22.9mg of Compound 2e (0.12 mmol, N-diisopropylethylamine 25.8mg (0.2 mmol), catalyst II-36 (0.01 mmol) and 1mL of dichloromethane were added to a reaction flask, stirred and mixed well, reacted at 25℃for 12h, TLC showed complete reaction, and concentrated direct concentration column chromatography (petroleum ether/ethyl acetate, v/v=3/1) gave 47.0mg of product I-70.
Characterization data: 88% yield, white powder, melting point: 141-143 ℃; 1 H NMR(400MHz,CDCl 3 )δ7.87(d,J＝8.3Hz,2H),7.82(s,1H),7.40-7.34(m,3H),7.19(s,1H),6.79(s,1H),2.98-2.80(m,6H),2.69(td,J＝7.3,3.3Hz,2H),2.48(s,3H),2.11(p,J＝7.5Hz,2H),2.00(p,J＝7.4Hz,2H). 13 C NMR(100MHz,CDCl 3 )δ156.16,153.96,152.43,146.10,145.50,143.02,135.30,132.71,129.94,128.95,125.42,124.07,118.71,117.47,114.54,33.42,32.42,31.76,25.61,25.58,21.96；
HRMS(ESI)m/z calcd for C 25 H 25 NO 5 S 2 [M+H] + ＝484.1252,found＝484.1227；
The ee value was 98％,t R (major)＝11.4min,t R (minor)＝16.3min(Chiralcel AD-H,λ＝254nm,30％i-PrOH/hexane,flow rate＝1.0mL/min)；
from the above nuclear magnetism and mass spectrum data, the obtained product had the correct structure.
The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.
Example chiral Sulfur Compounds for asymmetric catalytic reactions
The chiral sulfur compound provided by the invention can be used as a chiral catalyst, can induce the synthesis of a series of chiral compounds, and has wide application prospects in asymmetric catalysis and drug synthesis.
The foregoing description of the preferred embodiments of the invention is not intended to limit the invention to the precise form disclosed, and any such modifications, equivalents, and alternatives falling within the spirit and scope of the invention are intended to be included within the scope of the invention.

Claims (6)

1. A chiral sulfur compound is characterized by comprising the following specific structural formula:
2. the method for producing a chiral sulfur compound of claim 1, comprising the steps of:
under the action of chiral quaternary phosphonium salt catalyst, adding the compound A and the compound C into an organic solvent, then adding alkali, and reacting to obtain the chiral sulfur compound, wherein the synthetic route is as follows:
wherein R is 2 Is p-toluenesulfonyl; LG is H or halogen or ester group;
chiral quaternary phosphonium salt catalystOr (b)
Wherein R is 2 Is benzenesulfonyl or m-xylene sulfonyl; LG is H or halogen or ester group;
chiral quaternary phosphonium salt catalyst
3. The method for preparing chiral sulfur compound according to claim 2, wherein the organic solvent is carbon tetrachloride dichloromethane, N-dimethylformamide, chloroform, acetonitrile, 1, 2-dichloroethane, cyclohexane, N-hexane, N-heptane, petroleum ether, hexafluoroisopropanol, trifluoroethanol, methanol, ethanol, dimethyl sulfoxide, tetrahydrofuran, diethyl ether, anisole, methyl tert-butyl ether, ethyl acetate, methyl acetate, toluene, chlorobenzene, xylene or m-trimethylbenzene.
4. The method for producing a chiral sulfur compound according to claim 2, wherein the base is N, N-diisopropylethylamine, triethylamine, DBU, DABCO, potassium tert-butoxide, N-butyllithium, sodium carbonate, sodium hydrogencarbonate, lithium carbonate, potassium dihydrogenphosphate, dipotassium hydrogenphosphate, potassium phosphate, potassium carbonate, potassium hydrogencarbonate, potassium phosphate trihydrate, sodium hydroxide, lithium hydroxide, potassium hydroxide, cesium hydroxide, sodium hydrogen is potassium phosphate heptahydrate.
5. The process for producing a chiral sulfur compound according to claim 2, wherein the reaction temperature is-78 to 60 ℃ and the reaction time is 1 to 80 hours.
6. Use of a chiral sulfur compound of claim 1 for catalyzing asymmetric catalytic reactions of benzaldehyde and diethyl zinc.
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A.N. Serreqi等.Kinetic resolution of sulfoxides with pendant acetoxy groups using cholesterol esterase: substrate mapping and an empirical rule for chiral phenols.《Can. J. Chem.》.1995,第73卷1357-1367. *
Kinetic resolution of sulfoxides with pendant acetoxy groups using cholesterol esterase: substrate mapping and an empirical rule for chiral phenols;A.N. Serreqi等;《Can. J. Chem.》;第73卷;1357-1367 *

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