Method for synthesizing chiral sulfoxide compounds by allylation reaction

Abstract

The invention discloses a method for synthesizing a chiral sulfoxide compound by allylation reaction, comprising the following steps: mixing a compound 1 and a cinchona alkaloid catalyst, adding a first organic solvent to obtain a mixed solution; uniformly dispersing a compound 2 in a second organic solvent to obtain a solution of the compound 2, and o C, adding the compound 2 solution to the mixed solution, monitoring the reaction by thin layer chromatography under stirring, and after the reaction is completed, performing reduced pressure distillation and column chromatography separation to obtain a chiral sulfoxide compound. The method of the present invention has good substrate adaptability, and generates a composite chiral sulfoxide compound containing C-S axial chirality and sulfur center chirality through oxyallyl alkylation reaction. The chiral sulfoxide compound has diastereoselectivity and enantioselectivity, has high stereoselectivity, and can be used as an organic catalyst for asymmetric reduction reactions.

Description

Technical Field

[0001] The invention belongs to the technical field of organic chemical synthesis, and specifically relates to a method for synthesizing a chiral sulfoxide compound through an allylation reaction. Background Art

[0002] The chiral sulfoxide skeleton is not only an important component of many sulfoxide drugs (such as esomeprazole, sulforaphane and sparsomycin), but also an important skeleton for the composition of many chiral sulfoxide ligands. The chiral sulfoxide skeleton has some obvious advantages over the traditional ligand skeleton. The polarization between the sulfur and oxygen bonds can generate a certain polar charge between sulfur and oxygen. This polarization can coordinate with Lewis acids and transition metals during chemical reactions, and can effectively transfer chiral information to α, β or more distant reaction sites. In recent years, many chiral sulfoxide compounds can be used as a class of universal chiral ligands, and typical examples mainly include bissulfoxide ligands (Liao, J., et al. Hydrogen-Bond-Promoted Palladium Catalysis: AllylicAlkylation of Indoles with Unsymmetrical 1,3-Disubstituted Allyl AcetatesUsing Chiral Bis(sulfoxide) Phosphine Ligands. Angew. Chem., Int. Ed. , 2013, 52 , 4207.), sulfoxide olefin ligands (Xu, M.-H., et al. Design of Chiral Sulfoxide–Olefins as a New Class of Sulfur-Based Olefin Ligands for Asymmetric Catalysis. Org. Lett. , 2011, 13 , 3410.), sulfoxide nitrogen ligands and sulfoxide phosphorus nitrogen ligands (Suzuki, Y., et al. New chiralo-(phosphinoamido)phenyl sulfoxide ligands in palladium-catalyzed asymmetricallylic alkylations. Tetrahedron Lett ., 1998, 39 , 6499.).

[0003] At the same time, a variety of molecules containing chiral sulfoxide skeletons can also be used as catalysts to achieve some important asymmetric catalytic reactions (Ellman, JA, et al. Enantioselective Aza-Henry Reaction with an N-Sulfinyl Urea Organocatalyst. J. Am. Chem. Soc ., 2007, 129 , 15110.; Ellman, J.A., et al.).

[0004] In summary, chiral sulfoxide skeletons have become an attractive research direction. In the past few decades, chemists have been committed to developing a variety of methods to construct chiral sulfoxide skeletons, including asymmetric oxidation, desymmetrization, anti-Michael addition and asymmetric Pauson-Khand reaction. However, these methods are limited to the synthesis of single-center chiral sulfoxides. As the composite chiral sulfoxide skeleton has been proven to have important application value in asymmetric reactions (Jiang, X.-F., et al. Apractical synthesis of novel chiral sulfoxide-nitrogen ligands. Tetrahedron ,2016, 72 , 2671.), the development and synthesis of compounds containing complex chiral sulfoxide skeletons has gradually become a hot topic in scientific research. However, the current methods for synthesizing complex chiral sulfoxide skeletons are very limited, especially the method of efficiently preparing complex chiral sulfoxide skeletons by one step is even more scarce. Summary of the invention

[0005] In view of the deficiencies of the prior art, the object of the present invention is to provide a method for synthesizing a chiral sulfoxide compound by an allylation reaction, which can prepare a chiral sulfoxide compound containing CS axial chirality in one step with high selectivity, and the chiral sulfoxide compound has the general structural formula:

[0006] , wherein R is an aromatic group.

[0007] The purpose of the present invention is achieved through the following technical solutions.

[0008] A method for synthesizing a chiral sulfoxide compound by allylation reaction comprises the following steps:

[0009] Compound 1 and cinchona alkaloid catalyst are mixed, and a first organic solvent is added to obtain a mixed solution; Compound 2 is uniformly dispersed in a second organic solvent to obtain a solution of Compound 2, and the mixture is heated to -40 to -20 oC, adding the compound 2 solution to the mixed solution, monitoring the reaction by thin layer chromatography under stirring, and after the reaction is completed, performing vacuum distillation and column chromatography separation to obtain a chiral sulfoxide compound;

[0010] The compound 1 is 3,5-di-tert-butyl-2-(tert-butylsulfinyl)phenol, and the structural formula of 3,5-di-tert-butyl-2-(tert-butylsulfinyl)phenol is ;

[0011] The general structural formula of the compound 2 is , wherein R is an aryl group;

[0012] The cinchona alkali catalyst is 1,4-di(dihydroquinine)anthraquinone, and the structural formula of 1,4-di(dihydroquinine)anthraquinone is ;

[0013] Calculated by amount, the ratio of compound 1, compound 2 and cinchona alkaloid catalyst is (2-4):1:0.15.

[0014] In the above technical solution, the first organic solvent is anhydrous tetrahydrofuran, and the second organic solvent is anhydrous tetrahydrofuran.

[0015] In the above technical solution, the ratio of the amount of compound 1, the volume of the first organic solvent and the volume of the second organic solvent is (0.1~0.3):3:(0.5~1.5), the unit of the amount of the substance is mmol, and the unit of the volume is mL.

[0016] In the above technical solution, the reaction time is 4 to 7 days.

[0017] In the above technical solution, the developing solvent of the column chromatography is a mixture of petroleum ether and ethyl acetate, and the ratio of petroleum ether to ethyl acetate is (4-8):1 by volume.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] (1) The method of the present invention has good substrate adaptability. The compound 2 used is an achiral carbonate adduct. Under the catalysis of a low-cost and environmentally friendly cinchona alkali catalyst, an allylation reaction (oxyallyl alkylation reaction) is performed to generate a composite chiral sulfoxide compound containing CS axial chirality and sulfur center chirality.

[0020] (2) The diastereomeric excess (DR value) of the chiral sulfoxide compound is greater than 19:1, and the enantiomeric excess (EE value) is greater than 75%. Therefore, the chiral sulfoxide compound has diastereoselectivity and enantioselectivity and has high stereoselectivity.

[0021] (3) The chiral sulfoxide compound of the present invention can be used as an organic catalyst for asymmetric reduction reaction. The chiral sulfoxide compound of the present invention is used as a catalyst to catalyze the enantioselective synthesis of a chiral secondary alcohol compound. The preparation method of the chiral secondary alcohol compound does not require hydrogen and high pressure conditions, and the reaction is safer and milder, and does not require an alkaline environment. The chiral sulfoxide compound itself does not contain metal and is green and environmentally friendly. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 1;

[0023] Figure 2 This is the NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 1;

[0024] Figure 3 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 2;

[0025] Figure 4 This is the NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 2;

[0026] Figure 5 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 3;

[0027] Figure 6 This is the NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 3;

[0028] Figure 7 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 4;

[0029] Figure 8 This is the NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 4;

[0030] Fig. 9 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 5;

[0031] Fig.10 This is the NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 5;

[0032] Fig.11 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 6;

[0033] Fig.12 This is the NMR fluorine spectrum of the chiral sulfoxide compound prepared in Example 6;

[0034] Fig.13 This is the NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 6;

[0035] Fig.14 This is the H NMR spectrum of the chiral secondary alcohol compound prepared in Example 7;

[0036] Fig.15 This is the NMR carbon spectrum of the chiral secondary alcohol compound prepared in Example 7. DETAILED DESCRIPTION

[0037] The technical solution of the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments.

[0038] In the following examples, compound 1 is 3,5-di-tert-butyl-2-(tert-butylsulfinyl)phenol, which was prepared according to the literature Allen, CCR, et al. Chemoenzymatic synthesis of enantiopure hydroxysulfoxides derived from substituted arenes.

[0039] Org. Biomol. Chem ., 2016, 14 , 2651. Synthesis, the structural formula of 3,5-di-tert-butyl-2-(tert-butylsulfinyl)phenol is .

[0040] In the following examples, Compound 2a, Compound 2b, Compound 2c, Compound 2d, Compound 2e and Compound 2f are respectively used as Compound 2, and each is prepared according to the literature Cheng, J.-P., et al. Access to P-chiral phosphineoxides by enantioselective allylic alkylation of bisphenols. Chem. Sci ., 2019, 10 , 4322. Synthesis;

[0041] The structural formulas of Compound 2a, Compound 2b, Compound 2c, Compound 2d, Compound 2e and Compound 2f are as follows:

[0042]

[0043] In the following examples, benzaldehyde was purchased from Tianjin Xiensi Biochemical Technology Co., Ltd.

[0044] In the following examples, the diethyl zinc reagent was purchased from Tianjin Xiensi Biochemical Technology Co., Ltd. The diethyl zinc reagent was a mixture of diethyl zinc and toluene, and the concentration of diethyl zinc in the diethyl zinc reagent was 1 mol / L;

[0045] In the following examples, anhydrous tetrahydrofuran was purchased from Bailingwei Technology Co., Ltd.;

[0046] Petroleum ether was purchased from Tianjin Binhai New Area Guangshunda Reagent Co., Ltd.;

[0047] Ethyl acetate was purchased from Tianjin Binhai New Area Guangshun Da Reagent Co., Ltd.

[0048] In the following embodiments, the NMR carbon spectrum ( 1 H NMR、C NMR( 13 C NMR) and NMR fluorine spectroscopy ( 9 F NMR) was measured by a Bruker-DPX 400 nuclear magnetic resonance instrument.

[0049] In the following examples, high-resolution mass spectra were measured by a Shimadzu liquid chromatograph from Japan.

[0050] In the following examples, the specific rotation ([α] D 25 ) The Autopol IV automatic polarimeter produced by Rudolph Company of the United States was used at 25 o C. The test was conducted under the D line of a sodium lamp. The concentration (c) of the test sample was 0.5 g / mL. The solvent of the test sample was chloroform (CHCl3). The test sample was one of the chiral sulfoxide compounds prepared in Examples 1 to 6.

[0051] In the following examples, the cinchona alkali catalyst is 1,4-di(dihydroquinine)anthraquinone ((DHQ)2AQN), which was purchased from Daicel Pharmaceutical Chiral Technology (Shanghai) Co., Ltd. The structural formula of 1,4-di(dihydroquinine)anthraquinone is .

[0052] The chiral sulfoxide compound was confirmed by liquid chromatography (HPLC) to have CS axial chirality (aR configuration) and sulfur center chirality (S configuration). Example 1

[0053]

[0054] A method for synthesizing a chiral sulfoxide compound by allylation reaction comprises the following steps:

[0055] Compound 1 (0.2 mmol) and cinchona alkaloid catalyst (0.015 mmol) were placed in a 25 mL Schlenk reaction tube and mixed, and 3 mL of anhydrous tetrahydrofuran (THF, the first organic solvent) was added to obtain a mixed solution; Compound 2a (0.1 mmol) was dissolved in 1 mL of anhydrous tetrahydrofuran (the second organic solvent) to obtain a solution of Compound 2, and the mixture was heated at -30 °C. oC, the compound 2 solution was added to the mixed solution, and the reaction was monitored by thin layer chromatography (TLC) under stirring. The reaction was completed after 5.5 days, and the mixture was distilled under reduced pressure and separated by column chromatography (the developing solvent for the column chromatography was a mixture of petroleum ether and ethyl acetate, and the ratio of petroleum ether to ethyl acetate was 4:1 by volume) to obtain a chiral sulfoxide compound (3a) with a yield of 75%.

[0056] The diastereomeric excess (dr value) of the chiral sulfoxide compound is greater than 19:1, and the enantiomeric excess (ee value) of the chiral sulfoxide compound is 90%.

[0057] Figure 1 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 1. Figure 2 The NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 1 is as follows: Figure 1 and Figure 2 As shown, the NMR of the chiral sulfoxide compound prepared in Example 1 is: 1 H NMR (400 MHz, CDCl3) δ 7.43-7.37 (m, 5H), 7.14 (s, 1H), 6.91 (s, 1H), 6.55 (d, J = 9.4 Hz, 2H), 5.28 (s, 2H), 4.99 (d, J = 14.2 Hz, 1H), 4.85 (d, J =14.2 Hz, 1H), 1.56 (s, 9H), 1.36 (s, 9H), 1.29 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 165.6, 159.4, 155.9, 152.8, 135.8, 135.0, 129.1 (2C), 128.3 (2C), 128.1 (2C), 117.3 (2C), 110.2, 67.6, 66.6, 58.5, 37.4, 35.4, 33.5 (3C), 31.1 (3C), 27.4 (3C).

[0058] The high resolution mass spectrum of the chiral sulfoxide compound prepared in Example 1 is: HRMS (ESI): m / z calculated for C 29 H 40 NaO4S [M+Na] + : 507.2540, found: 507.2542.

[0059] The specific rotation of the chiral sulfoxide compound prepared in Example 1 is: [α] D 25 = +11.6 (c = 0.5, CHCl3). Example 2

[0060]

[0061] A method for synthesizing a chiral sulfoxide compound by allylation reaction is basically the same as the method in Example 1, except that compound 2a in Example 1 is replaced by compound 2b. The chiral sulfoxide compound (3b) prepared by the method in Example 2 has a yield of 69%.

[0062] The diastereomeric excess (dr value) of the chiral sulfoxide compound prepared by the method of Example 2 is greater than 19:1, and the enantiomeric excess (ee value) of the chiral sulfoxide compound is 88%.

[0063] Figure 3 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 2. Figure 4 The NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 2 is as follows: Figure 3 and Figure 4 As shown, the NMR of the chiral sulfoxide compound prepared in Example 2 is: 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 9.1 Hz, 1H), 7.86 (t, J = 9.5 Hz, 2H),7.57 (d, J = 6.8 Hz, 1H), 7.51 (s, 2H), 7.44 (s, 1H), 7.08 (s, 1H), 6.83 (s,1H), 6.47 (d, J = 5.3 Hz, 2H), 5.70 (s, 2H), 4.93 (d, J = 14.2 Hz, 1H), 4.80 (d, J = 14.1 Hz, 1H), 1.51 (s, 9H), 1.30 (s, 9H), 1.22 (s, 9H); 13C NMR (101 MHz, CDCl3) δ 165.6, 159.3, 155.8, 152.8, 135.0, 133.7, 131.7, 131.2, 129.4,129.3, 128.7 (2C), 127.5, 126.6, 126.0, 125.3, 123.5, 117.3, 110.1, 67.6,65.1, 58.5, 37.4, 35.4, 33.5 (3C), 31.1 (3C), 27.4 (3C).

[0064] The high resolution mass spectrum of the chiral sulfoxide compound prepared in Example 2 is: HRMS (ESI): m / z calculated for C 33 H 43 O4S [M+H] + = 535.2877, found 535.2880.

[0065] The specific rotation of the chiral sulfoxide compound prepared in Example 2 is: [α] D 25 = +35.6 (c = 0.5, CHCl3). Example 3

[0066]

[0067] A method for synthesizing a chiral sulfoxide compound by allylation reaction is basically the same as the method in Example 1, except that compound 2a in Example 1 is replaced by compound 2c. The chiral sulfoxide compound (3c) prepared by the method in Example 3 has a yield of 72%.

[0068] The diastereomeric excess value dr of the chiral sulfoxide compound prepared by the method of Example 3 is greater than 19:1, and the enantiomeric excess value (ee value) of the chiral sulfoxide compound is 88%.

[0069] Figure 5 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 3. Figure 6 The NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 3 is as follows: Figure 5 and Figure 6 As shown, the NMR of the chiral sulfoxide compound prepared in Example 3 is: 1 H NMR (400 MHz, CDCl3) δ 7.34 (dd, J = 5.1, 1.2 Hz, 1H), 7.14 (d, J = 3.9 Hz,1H), 7.12 (d,J = 1.7 Hz, 1H), 7.00 (s, 1H), 6.89 (s, 1H), 6.55 (s, 1H), 6.50(s, 1H), 5.41 (s, 2H), 4.95 (d, J = 16.0 Hz, 1H), 4.82 (d, J = 14.2 Hz, 1H), 1.54(s, 9H), 1.34 (s, 9H), 1.28 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 165.4, 159.4,155.9, 152.8, 137.7, 134.9, 129.4, 128.3, 126.9 (2C), 126.8, 117.3, 110.2,67.5, 60.9, 58.5, 37.4, 35.4, 33.5 (3C), 31.1 (3C), 27.4 (3C).

[0070] The high resolution mass spectrum of the chiral sulfoxide compound prepared in Example 3 is: HRMS (ESI): m / z calculated for C 27 H 39 O4S2[M+H] + : 491.2284, found: 491.2288.

[0071] The specific rotation of the chiral sulfoxide compound prepared in Example 3 is: [α] D 25 = +36.4 (c = 0.5, CHCl3). Example 4

[0072]

[0073] A method for synthesizing a chiral sulfoxide compound by allylation reaction is basically the same as the method in Example 1, except that the compound 2a in Example 1 is replaced by the compound 2d. The chiral sulfoxide compound (3d) prepared by the method in Example 4 has a yield of 71%.

[0074] The diastereomeric excess (dr value) of the chiral sulfoxide compound prepared by the method of Example 4 is greater than 19:1, and the enantiomeric excess (ee value) of the chiral sulfoxide compound is 82%.

[0075] Figure 7 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 4. Figure 8The NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 4 is as follows: Figure 7 and Figure 8 As shown, the NMR of the chiral sulfoxide compound prepared in Example 4 is: 1 H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.2 Hz, 2H),7.09 (s, 1H), 6.84 (s, 1H), 6.51 (s, 1H), 6.47 (s, 1H), 5.17 (s, 2H), 4.92(d, J = 14.1 Hz, 1H), 4.78 (d, J = 14.1 Hz, 1H), 1.50 (s, 9H), 1.30 (s, 9H), 1.23(s, 9H); 13 C NMR (101 MHz, CDCl3) 165.4, 159.4, 155.9, 152.8, 135.0 (2C), 131.8, 129.9 (2C), 129.4 (2C), 126.3, 122.3, 117.4, 110.3, 67.7, 65.8, 58.5,37.4, 35.4, 33.5 (3C), 31.1 (3C), 27.4 (3C).

[0076] The high resolution mass spectrum of the chiral sulfoxide compound prepared in Example 4 is: HRMS (ESI): m / z calculated for C 29 H 40 BrO4S [M+H] + : 563.1825, found: 563.1828.

[0077] The specific rotation of the chiral sulfoxide compound prepared in Example 4 is: [α] D 25 = +43.6 (c = 0.5, CHCl3). Example 5

[0078]

[0079] A method for synthesizing a chiral sulfoxide compound by allylation reaction is basically the same as the method in Example 1, except that compound 2a in Example 1 is replaced by compound 2e. The reaction is completed for 7 days. The chiral sulfoxide compound (3e) prepared by the method in Example 5 has a yield of 41%.

[0080] The diastereomeric excess (dr value) of the chiral sulfoxide compound prepared by the method of Example 5 is greater than 19:1, and the enantiomeric excess (ee value) of the chiral sulfoxide compound is 84%.

[0081] Fig. 9 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 5. Fig.10 The NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 5 is as follows: Fig. 9 and Fig.10 As shown, the NMR of the chiral sulfoxide compound prepared in Example 5 is: 1 H NMR (400 MHz, CDCl3) δ 7.22 – 7.18 (m, 2H), 7.11 – 7.09 (m, 2H), 7.04(s, 1H), 6.81 (s, 1H), 6.43 (d, J = 8.0 Hz, 2H), 5.14 (s, 2H), 4.88 (d, J = 16.0Hz, 1H), 4.74 (d, J = 12.0 Hz, 1H), 2.28 (s, 3H), 1.46 (s, 9H), 1.26 (s, 9H), 1.19 (s, 9H).; 13 C NMR (101 MHz, CDCl3) δ 165.6, 159.4, 155.9, 152.8, 138.1,135.1, 132.8, 129.3 (2C), 129.0 (2C), 128.3 (2C), 117.3, 110.2, 67.7, 66.6,58.5, 37.4, 35.4, 33.5 (3C), 31.1 (3C), 27.4 (3C), 21.2.

[0082] The high resolution mass spectrum of the chiral sulfoxide compound prepared in Example 5 is: HRMS (ESI): m / z calculated for C 30 H 43 O4S [M+H] + = 499.2877, found 499.2880.

[0083] The specific rotation of the chiral sulfoxide compound prepared in Example 5 is: [α] D 25 = +43.6 (c = 0.5, CHCl3). Example 6

[0084]

[0085] A method for synthesizing a chiral sulfoxide compound by allylation reaction is basically the same as the method in Example 1, except that compound 2a in Example 1 is replaced by compound 2f. The chiral sulfoxide compound (3f) prepared by the method in Example 6 has a yield of 72%.

[0086] The diastereomeric excess (dr value) of the chiral sulfoxide compound prepared by the method of Example 6 is greater than 19:1, and the enantiomeric excess (ee value) of the chiral sulfoxide compound is 76%.

[0087] Fig.11 This is the H NMR spectrum of the chiral sulfoxide compound prepared in Example 6. Fig.12 This is the NMR fluorine spectrum of the chiral sulfoxide compound prepared in Example 6. Fig.13 The NMR carbon spectrum of the chiral sulfoxide compound prepared in Example 6 is as follows: Fig.11 , Fig.12 and Fig.13 As shown, the NMR of the chiral sulfoxide compound prepared in Example 6 is: 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 7.8 Hz, 1H), 7.58 – 7.56 (m, 2H), 7.47 – 7.44 (m, 1H),7.13 (d, J = 1.7 Hz, 1H), 6.89 (d, J = 1.7 Hz, 1H), 6.56 (d, J = 11.2 Hz, 2H), 5.45(dd, J = 2.2, 1.1 Hz, 2H), 4.95 (s, 1H), 4.84 (d, J = 14.1 Hz, 1H), 1.54 (s,9H), 1.35 (s, 9H), 1.27 (s, 9H); 9 F NMR (376 MHz, CDCl3) δ -59.5; 13 C NMR (101MHz, CDCl3) δ 165.2, 159.3, 155.9, 152.8, 134.8, 134.0, 132.1, 130.0 (2C), 129.5 (2C), 128.4 (q, J = 5.9 Hz), 126.2 (q,J = 5.7 Hz), 124.1(q, J = 273.9 Hz),117.3, 110.2, 67.5, 63.1, 58.6, 37.4, 35.4, 33.5 (3C), 31.1 (3C), 27.4 (3C).

[0088] The high resolution mass spectrum of the chiral sulfoxide compound prepared in Example 6 is: HRMS (ESI): m / z calculated for C 30 H 40 F3O4S [M+H] + = 553.2594, found 553.2597.

[0089] The specific rotation of the chiral sulfoxide compound prepared in Example 6 is: [α] D 25 = +31.4 (c = 0.5, CHCl3). Example 7

[0090]

[0091] Benzaldehyde (0.4 mmol) and the chiral sulfoxide compound (3c) (0.02 mmol) prepared in Example 3 were placed in a 25 mL Shrek tube, 4 mL of toluene was added, the air in the Shrek tube was evacuated and replaced with argon, and diethyl zinc reagent (400 μL) was quickly added under argon atmosphere, and the reaction was carried out at room temperature for 48 hours. After the reaction was completed, the mixture was distilled under reduced pressure and separated by column chromatography (the developing solvent for column chromatography was a mixture of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate was 20:1) to obtain a chiral secondary alcohol compound with a yield of 44% and an enantiomeric ratio (er value) of 67.5:32.5.

[0092] Fig.14 This is the H NMR spectrum of the chiral secondary alcohol compound prepared in Example 7. Fig.15 The NMR carbon spectrum of the chiral secondary alcohol compound prepared in Example 7 is as follows: Fig.14 and Fig.15 As shown, the NMR of the chiral secondary alcohol compound prepared in Example 7 is: 1 H NMR (400 MHz, CDCl3) δ 7.40 – 7.32 (m, 5H), 4.55 (t, J = 8.0 Hz,1H), 1.87 - 1.70 (m, 2H), 0.94 (t, J = 8.0 Hz, 3H);13 C NMR (101 MHz, CDCl3) δ144.7, 128.4 (2C), 127.4, 126.1 (2C), 75.9, 31.9, 10.23.

[0093] The high resolution mass spectrum of the chiral secondary alcohol compound prepared in Example 7 is: HRMS (ESI): m / z calculated for C9H 13 O[M+H] + = 137.0961, found 137.0963.

[0094] Zeng et al. have disclosed a manganese catalyst for ketone hydrogenation, which can enantioselectively hydrogenate 1-phenyl-1-propanone to (R)-1-phenyl-1-propanol (i.e., the chiral secondary alcohol compound in Example 7). However, the reaction needs to be carried out under hydrogen and high pressure conditions, which is very dangerous. In addition, the use of alkaline solvents causes certain environmental pollution. In addition, the steps for preparing the manganese catalyst are complicated and dangerous. The manganese catalyst itself is a metal catalyst, which may also have problems such as metal leakage and pollution (Zeng L, Yang H, Zhao M, et al. C1-Symmetric PNPLigands for Manganese-Catalyzed Enantioselective Hydrogenation of Ketones: Reaction Scope and Enantioinduction Model. ACS Catal ., 2020, 10 , 13794-13799).

[0095] The present invention is described above by way of example. It should be noted that, without departing from the core of the present invention, any simple deformation, modification or other equivalent replacement that can be made by those skilled in the art without inventive effort falls within the protection scope of the present invention.

Claims

1. A method for synthesizing a chiral sulfoxide compound by allylation reaction, characterized in that: The structural formula of the chiral sulfoxide compound is ; The method comprises the following steps: Compound 1 and cinchona alkaloid catalyst are mixed, and a first organic solvent is added to obtain a mixed solution; Compound 2 is uniformly dispersed in a second organic solvent to obtain a solution of Compound 2, and the mixture is heated to -40 to -20 o C, adding the compound 2 solution to the mixed solution, monitoring the reaction by thin layer chromatography under stirring, and after the reaction is completed, performing vacuum distillation and column chromatography separation to obtain a chiral sulfoxide compound; The compound 1 is 3,5-di-tert-butyl-2-(tert-butylsulfinyl)phenol, and the structural formula of 3,5-di-tert-butyl-2-(tert-butylsulfinyl)phenol is ; The general structural formula of the compound 2 is , wherein R is thiophene; The cinchona alkali catalyst is 1,4-di(dihydroquinine)anthraquinone, and the structural formula of 1,4-di(dihydroquinine)anthraquinone is ; Calculated by amount, the ratio of compound 1, compound 2 and cinchona alkaloid catalyst is (2-4):1:0.

15.

2. The method according to claim 1, characterized in that: The first organic solvent is anhydrous tetrahydrofuran, and the second organic solvent is anhydrous tetrahydrofuran.

3. The method according to claim 1, characterized in that The ratio of the amount of the compound 1, the volume of the first organic solvent and the volume of the second organic solvent is (0.1-0.3):3:(0.5-1.5), the unit of the amount of the compound 1 is mmol, and the unit of the volume is mL.

4. The method according to claim 1, characterized in that: The reaction time is 4 to 7 days.

5. The method according to claim 1, characterized in that The developing solvent for column chromatography is a mixture of petroleum ether and ethyl acetate, and the ratio of petroleum ether to ethyl acetate is (4~8):1 by volume.

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