A process for the preparation of chiral sulfilimine compounds

Abstract

The application discloses a preparation method of a chiral sulfimine compound and belongs to the technical fields of visible light catalysis and organic synthesis. N -[(9 R )-6'-methoxyoctanosyl]-8-quinolinesulfonamide as a chiral ligand, fluorobenzene as a solvent, under the action of a copper salt and an oxidant, under visible light irradiation at room temperature in a protective atmosphere, the copper salt, the sulfenamide compound and N -[(9 R )-6'-methoxyoctanosyl]-8-quinolinesulfonamide form a copper complex, the copper complex enters an excited state under visible light irradiation, cleaves the oxidant through an energy transfer or single electron transfer process, generates a highly active free radical, the free radical activates an inert carbon-hydrogen bond to generate an alkyl free radical and reacts with the sulfenamide in the copper complex, asymmetric sulfuration of the inert carbon-hydrogen bond is realized, and the chiral sulfimine compound is obtained.

Description

Technical Field

[0001] This invention relates to the fields of visible light catalysis and organic synthesis technology, specifically to a method for preparing a chiral thioimine compound. Background Technology

[0002] The direct activation of inert C-H bonds to construct asymmetric carbon-heterobonds has long been a hot topic in organocatalysis. This synthetic strategy can directly and asymmetrically transform widely existing inert C-H bonds into carbon-halogen bonds, carbon-nitrogen bonds, carbon-oxygen bonds, carbon-sulfur bonds, etc., and has broad application prospects in the synthesis of natural products and drug molecules.

[0003] Because of the high bond energy of these inert C-H bonds, the very similar polarity between multiple C-H bonds, and the lack of a directing group for positioning, the traditional synthesis of chiral thioimine compounds usually requires expensive transition metal catalysis and involves harsh reaction conditions of high temperature and high pressure. Summary of the Invention

[0004] This invention provides a method for preparing chiral thioimine compounds, which effectively solves the technical problems of traditional synthesis methods that rely on expensive transition metal catalysis and require high temperature and high pressure conditions. This invention achieves efficient asymmetric sulfidation of inert C-H bonds of organic compounds under visible light irradiation at room temperature using inexpensive and readily available catalysts and reagents, obtaining chiral thioimine products with high yield and enantioselectivity, while reducing waste emissions.

[0005] The purpose of this invention is to provide a method for preparing a chiral thioimine compound, comprising the following steps: using a compound containing inert carbon-hydrogen bonds and a sulfenamide compound as raw materials, and... N -[(9 R Using 6′-methoxyoctanan-9-yl]-8-quinoline sulfonamide as a chiral ligand, and fluorobenzene as a solvent, under the action of copper salt and oxidant, and at room temperature and under a protective atmosphere, the chiral ligand forms a copper complex. The copper complex then cleaves the oxidant under visible light irradiation, generating active free radicals. These active free radicals activate inert C-H bonds to produce alkyl free radicals, which react with the sulfonamide in the copper complex, asymmetrically sulfidating the inert C-H bonds to obtain a chiral thioimine compound.

[0006] In a preferred embodiment, the molar ratio of the sulfenamide compound to the copper salt and the chiral ligand is 1:0.04:0.05, and the molar ratio of the sulfenamide compound to the oxidant is 1:4.

[0007] In a preferred embodiment, the molar ratio of the compound containing inert C-H bonds to the sulfenamide compound is 3-6:0.1.

[0008] In a preferred embodiment, the compound containing inert C-H bonds is toluene, xylene, methyl p-toluene, 3-methylthiophene, cyclohexane, 2,3-dimethylbutane, or n-pentane.

[0009] In a preferred embodiment, the sulfenamide compound is a sulfenamide compound containing a -CONH group.

[0010] In a preferred embodiment, the copper salt is copper tetraacetonitrile hexafluorophosphate; and the oxidant is di-tert-butyl peroxide.

[0011] In a preferred embodiment, the wavelength of the visible light is 455 nm.

[0012] In a preferred embodiment, the solvent may be replaced with a mixture of fluorobenzene and acetone.

[0013] In a preferred embodiment, after the reaction is completed, the solvent is removed by a rotary evaporator under reduced pressure to obtain the initial product. The initial product is then separated by column chromatography using petroleum ether and ethyl acetate to obtain a chiral thioimine compound.

[0014] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0015] This invention provides a method for preparing chiral thioimine compounds, using compounds containing inert C-H bonds and sulfenamide compounds as raw materials, and... N -[(9 R Using 6′-methoxyoctanol-9-yl]-8-quinoline sulfonamide as a chiral ligand, and with fluorobenzene as a solvent, under the action of copper salt and oxidant, and at room temperature and under a protective atmosphere, after irradiation with visible light, the copper salt, sulfenamide compound, and... N -[(9 R [-6′-methoxyoctanol-9-yl]-8-quinoline sulfonamide forms a copper complex. Under visible light irradiation, the copper complex enters an excited state and cleaves the oxidant through energy transfer or single electron transfer to generate highly active free radicals. These highly active free radicals activate inert C-H bonds to generate alkyl free radicals, which react with the sulfenamide in the copper complex to achieve asymmetric sulfidation of inert C-H bonds, yielding a chiral thioimine compound.

[0016] This invention constructs thioimine compounds with tetravalent sulfur chiral centers through enantioselective activation of inert C-H bonds. This invention can be carried out at room temperature, with low catalytic amount, high reaction efficiency, good enantioselectivity, and good versatility. Furthermore, utilizing visible light to provide the activation energy is a milder, more economical, efficient, and environmentally friendly activation mode. The copper salt used in this invention is inexpensive, and the catalyst is also inexpensive to manufacture, avoiding environmental pollution from heavy metals and other chemical additives. This invention utilizes photocatalysis, resulting in milder reaction conditions and excellent yield and enantioselectivity. The generated chiral thioimine compounds have broad application prospects in the synthesis of natural products and drug molecules, and have great potential for the efficient production of chiral thioimine compounds in the field of synthetic chemistry. Attached Figure Description

[0017] Figure 1 This is a schematic diagram of the visible light photoreactor used in this invention, wherein Figure A is the photoreactor and Figure B is a diagram of the visible light irradiation reaction.

[0018] Figure 2 The hydrogen spectrum of the sulfenamide compound containing the -CONH group prepared in this invention is shown.

[0019] Figure 3 The hydrogen spectrum of the chiral thioimine compound prepared in Example 1 of this invention.

[0020] Figure 4 The hydrogen spectrum of the chiral thioimine compound prepared in Example 2 of this invention.

[0021] Figure 5 The hydrogen spectrum of the chiral thioimine compound prepared in Example 3 of this invention.

[0022] Figure 6 The hydrogen spectrum of the chiral thioimine compound prepared in Example 4 of this invention.

[0023] Figure 7 The hydrogen spectrum of the chiral thioimine compound prepared in Example 5 of this invention.

[0024] Figure 8 The hydrogen spectrum of the chiral thioimine compound prepared in Example 6 of this invention.

[0025] Figure 9 The hydrogen spectrum of the chiral thioimine compound prepared in Example 7 of this invention. Detailed Implementation

[0026] To enable those skilled in the art to better understand and implement the technical solutions of this invention, the invention is further described below with reference to specific embodiments. However, the embodiments are not intended to limit the invention. Unless otherwise specified, the following test methods and detection methods are conventional methods; unless otherwise specified, the reagents and raw materials are commercially available.

[0027] When synthesizing asymmetric carbon-heterobonds by directly activating inert C-H bonds, the high bond energy of inert C-H bonds, the very similar polarity among multiple C-H bonds, and the lack of a directing group for positioning, traditional methods for synthesizing chiral thioimine compounds typically require expensive transition metal catalysis and involve harsh reaction conditions of high temperature and high pressure. Based on the above technical problems, this invention provides a method for preparing chiral thioimine compounds.

[0028] The technical solution of the present invention will be described in detail below.

[0029] This invention provides a method for preparing a chiral thioimine compound, comprising the following steps: using a compound containing inert C-H bonds and a sulfenamide compound as raw materials, and... N -[(9 R Using 6′-methoxyoctanol-9-yl]-8-quinoline sulfonamide as a chiral ligand, and with fluorobenzene as a solvent, under the action of copper salt and oxidant, and at room temperature and under a protective atmosphere, upon exposure to visible light, as shown... Figure 1 As shown, the copper salt and sulfenamide compounds form a copper complex with the chiral ligand. Under visible light irradiation, the copper complex decomposes the oxidant to generate highly active free radicals. These highly active free radicals activate inert C-H bonds to generate alkyl free radicals, which then react with the sulfenamide in the copper complex to achieve asymmetric sulfidation of the inert C-H bonds, yielding a chiral thioimine compound.

[0030] In the above technical solution, a thioimine compound with a tetravalent sulfur chiral center is enantioselectively constructed by activating inert C-H bonds. The reaction can be carried out at room temperature, with low catalytic amount, high efficiency, good enantioselectivity, and good versatility. The copper salt used in this invention is inexpensive, and the catalyst is inexpensive to manufacture, avoiding environmental pollution from heavy metals and other chemical additives. This invention utilizes photocatalysis, resulting in milder reaction conditions and excellent yield and enantioselectivity.

[0031] To achieve optimal enantioselectivity and obtain better yields of chiral thioimine compounds, the molar ratio of the sulfenamide compound to the copper salt and chiral ligand is 1:0.04:0.05. Other molar ratios lead to a decrease in reaction yield. The molar ratio of the sulfenamide compound to the oxidant is 1:4. Excess or insufficient oxidant will also lead to a decrease in reaction yield.

[0032] To further improve the yield of chiral thioimine compounds, the molar ratio of the compound containing inert C-H bonds to the sulfenamide compound is 3~6:0.1. When the molar amount of the compound containing inert C-H bonds is less than 3 as defined herein, the amount of the compound containing inert C-H bonds is too small, and the reaction yield will decrease under the same reaction time. When the molar amount of the compound containing inert C-H bonds is greater than 6 as defined herein, there is too much solvent for the reaction, and the atom economy decreases.

[0033] It should be noted that the compounds containing inert C-H bonds used in this invention are toluene, xylene, methyl p-toluene, 3-methylthiophene, cyclohexane, 2,3-dimethylbutane, or n-pentane. The sulfenamide compounds are sulfenamide compounds containing -CONH groups. The copper salt is copper tetraacetonitrile hexafluorophosphate; the oxidizing agent is di-tert-butyl peroxide.

[0034] To further ensure the reaction yield, the wavelength of the visible light can be 455 nm. 455 nm is the maximum absorption wavelength of the complex formed by the sulfenamide compound, copper salt, and chiral ligand. Therefore, irradiation with visible light at 455 nm is the most effective. In the early experiments, the present invention also tried wavelengths of 390 nm and 420 nm, but both wavelengths led to a decrease in the reaction yield.

[0035] To further improve the yield and purity of the chiral thioimine compound, the solvent was removed under reduced pressure using a rotary evaporator after the reaction to obtain the initial product. The initial product was then separated by column chromatography using petroleum ether and ethyl acetate to obtain the chiral thioimine compound.

[0036] The technical effects of the present invention will be described below through the following embodiments.

[0037] This invention first prepares a sulfenamide compound, comprising the following steps:

[0038] S1, under a nitrogen atmosphere, 26 mmol, or 3.47 g, of... N 1-Chlorosilicate imide was placed in a 250 mL reaction flask and dissolved in 50 mL of dichloromethane. 30 mmol (5.2 mL) of p-tert-butylthiophenol (compound A) was slowly added at 0 °C, and the reaction mixture was stirred at room temperature for 12 h. The organic solvent was removed from the reaction solution under reduced pressure using a rotary evaporator. The concentrated reaction solution was then washed with 50 mL of n-hexane, filtered, and the solid was washed with 20 mL of n-hexane. The filtrate was concentrated under reduced pressure using a rotary evaporator to obtain crude sulfenyl chloride C as an orange liquid. This was then diluted with 10 mL of dry tetrahydrofuran to obtain a tetrahydrofuran solution of sulfenyl chloride, i.e., a tetrahydrofuran solution of compound C.

[0039] S2, in another dried 250 mL reaction flask, 20 mmol (2.42 g) of benzamide, compound B, was dissolved in 80 mL of dried tetrahydrofuran. 60 mmol (2.4 g) of 60% sodium hydride was carefully added in portions at 0 °C, and the reaction mixture was stirred at room temperature for 2 h to obtain a tetrahydrofuran solution of sodium benzamide, compound B'. The reaction mixture was then cooled to -30 °C, and a tetrahydrofuran solution of sulfenyl chloride was added dropwise to the reaction system. The mixture was then placed at room temperature and stirred for 12 h. After the reaction was complete, 70 mL of ice water was added to quench the reaction. The aqueous phase was extracted with 80 mL of ethyl acetate, repeated three times. The organic phases were combined and dried over anhydrous sodium sulfate. The organic solvent was removed under reduced pressure using a rotary evaporator to obtain the crude product. Separation was achieved by silica gel column chromatography with a 5:1 volume ratio of petroleum ether and ethyl acetate to obtain sulfenamide, denoted as compound D, with a yield of 4.05 g and a yield of 71%.

[0040] The reaction pathway described above is shown below:

[0041] .

[0042] Example 1

[0043] A method for preparing a chiral thioimine compound includes the following steps:

[0044] Take a 10 mL dried Shrek tube containing a magnetic magnet, add 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L. The structural formula is as follows: The reaction system was then replaced with a nitrogen atmosphere by three evacuations. Subsequently, 6 mmol of toluene, 0.4 mmol (74 μL) of di-tert-butyl peroxide (DTBP) as the oxidant, and 1.0 mL of fluorobenzene were added under nitrogen purging. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography with petroleum ether and ethyl acetate in a 2:1 volume ratio to obtain a chiral thioimine compound, denoted as asymmetric sulfide product E, with a yield of 83% and an enantiomeric excess of 95% (ee value of 95%).

[0045] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0046] .

[0047] Example 2

[0048] A method for preparing a chiral thioimine compound includes the following steps:

[0049] Take a 10 mL dried Shrek tube containing a magnetic magnet, add 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L. Its structural formula is as follows: The reaction system was then replaced with a nitrogen atmosphere by three evacuations. Subsequently, under nitrogen purging, 6 mmol of xylene, 0.4 mmol (74 μL) of the oxidant di-tert-butyl peroxide (DTBP), and 1.0 mL of fluorobenzene were added. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography with a 2:1 volume ratio of petroleum ether and ethyl acetate to obtain a chiral thioimine compound, denoted as asymmetric sulfide product F, with a yield of 60% and an enantiomeric excess of 95% (ee value of 95%).

[0050] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0051] .

[0052] Example 3

[0053] A method for preparing a chiral thioimine compound includes the following steps:

[0054] Take a 10 mL dried Shrek tube containing a magnetic magnet, add 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L. Its structural formula is as follows: 3 mmol (451 mg) of methyl p-methylbenzoate was added, followed by three purgings to purge the reaction system into a nitrogen atmosphere. Then, under nitrogen purging, 0.4 mmol (74 μL) of the oxidant di-tert-butyl peroxide (DTBP), 0.5 mL of acetone, and 1.0 mL of fluorobenzene were added. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography with a 2:1 volume ratio of petroleum ether and ethyl acetate to obtain a chiral thioimine compound, designated as asymmetric sulfide product G, with a yield of 70% and an enantiomeric excess of 92%.

[0055] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0056] .

[0057] Example 4

[0058] A method for preparing a chiral thioimine compound includes the following steps:

[0059] Take a 10 mL dried Shrek tube containing a magnetic magnet, add 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L. Its structural formula is as follows: The reaction system was then replaced with a nitrogen atmosphere by three evacuations. Subsequently, 6 mmol of 3-methylthiophene, 0.4 mmol (74 μL) of the oxidant di-tert-butyl peroxide (DTBP), and 1.0 mL of fluorobenzene were added under nitrogen purging. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography with a 2:1 volume ratio of petroleum ether and ethyl acetate to obtain a chiral thioimine compound, denoted as asymmetric sulfide product H, with a yield of 53% and an enantiomeric excess of 81%.

[0060] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0061] .

[0062] Example 5

[0063] A method for preparing a chiral thioimine compound includes the following steps:

[0064] Take a 10 mL dried Shrek tube containing a magnetic magnet, add 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L. Its structural formula is as follows: The reaction system was then replaced with a nitrogen atmosphere by three evacuations. Subsequently, 6 mmol of cyclohexane, 0.4 mmol (74 μL) of the oxidant di-tert-butyl peroxide (DTBP), and 1.0 mL of fluorobenzene were added under nitrogen purging. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography with a 2:1 volume ratio of petroleum ether and ethyl acetate to obtain a chiral thioimine compound, designated as asymmetric sulfide product I, with a yield of 76% and an enantiomeric excess of 96%.

[0065] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0066] .

[0067] Example 6

[0068] A method for preparing a chiral thioimine compound includes the following steps:

[0069] Take a 10 mL dried Shrek tube containing a magnetic magnet, add 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L. Its structural formula is as follows: The reaction system was then replaced with a nitrogen atmosphere by three evacuations. Subsequently, 6 mmol of 2,3-dimethylbutane, 0.4 mmol (74 μL) of the oxidant di-tert-butyl peroxide (DTBP), and 1.0 mL of fluorobenzene were added under nitrogen purging. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography with a 2:1 volume ratio of petroleum ether and ethyl acetate to obtain a chiral thioimine compound, designated as asymmetric sulfide product J, with a yield of 32% and an enantiomeric excess of 94%.

[0070] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0071] .

[0072] Example 7

[0073] A method for preparing a chiral thioimine compound includes the following steps:

[0074] A 10 mL dried Shrek tube equipped with a magnetic magnet was used. 0.1 mmol (28.5 mg) of compound D, 0.004 mmol (1.5 mg) of copper tetraacetonitrile hexafluorophosphate, and 0.005 mmol (2.6 mg) of chiral ligand L (structural formula omitted) were added. The reaction system was then replaced with nitrogen gas by three evacuations. Subsequently, under nitrogen purging, 6 mmol of n-pentane, 0.4 mmol (74 μL) of the oxidant di-tert-butyl peroxide (DTBP), and 1.0 mL of fluorobenzene were added. The reaction was carried out at 25 °C for 48 h under 455 nm blue LED illumination. After the reaction, the reaction solvent was removed under reduced pressure using a rotary evaporator. The residual components were separated by silica gel column chromatography using petroleum ether and ethyl acetate in a 2:1 volume ratio to obtain a chiral thiamine compound, denoted as K, a mixture of sulfide products containing α, β, and γ sites, with a yield of 90%.

[0075] The synthetic route for the above-mentioned chiral thioimine compounds is shown below:

[0076] .

[0077] The structures of the sulfenamide compounds prepared in this invention, namely compound D, and the chiral thioimine compounds prepared in Examples 1 to 7 above were analyzed, and the results are as follows: Figures 2-9 As shown.

[0078] Depend on Figure 2 It can be seen that sulfenamide, i.e., compound D, is... 1 H NMR (400MHz, Chloroform-d) δ 7.86 –7.80 (m, 2H), 7.57 – 7.51 (m, 1H), 7.49 – 7.39 (m, 3H), 7.37 – 7.31 (m, 4H), 1.28 (s, 9H).

[0079] Depend on Figure 3 It can be seen that the asymmetric sulfidation product E of Example 1 1 H NMR (500MHz, Chloroform- d ) δ8.24 – 8.18 (m, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.48 – 7.36 (m, 5H), 7.29 (t, J =7.4 Hz, 1H), 7.21 (t, J = 7.5 Hz, 2H), 6.98 (d, J = 7.5 Hz, 2H), 4.63 (d, J = 12.4Hz, 1H), 4.23 (d, J = 12.3 Hz, 1H), 1.31 (s, 9H).

[0080] Depend on Figure 4 It can be seen that the asymmetric sulfidation product F of Example 2... 1 H NMR (500MHz, Chloroform- d ) δ8.22 – 8.17 (m, 2H), 7.54 – 7.48 (m, 2H), 7.48 – 7.40 (m, 3H), 7.39 (t, J = 7.1Hz, 2H), 7.02 (d, J = 7.7 Hz, 2H), 6.88 (d, J = 7.8 Hz, 2H), 4.61 (d, J= 12.4 Hz, 1H), 4.19 (d, J = 12.4 Hz, 1H), 2.31 (s, 3H), 1.32 (s, 9H).

[0081] Depend on Figure 5 It can be seen that the asymmetric sulfurization product G in Example 3... 1 H NMR (400MHz, Chloroform- d ) δ8.20 – 8.14 (m, 2H), 7.90 – 7.85 (m, 2H), 7.53 – 7.40 (m, 5H), 7.43 – 7.34(m, 2H), 7.03 (d, J = 8.3 Hz, 2H), 4.58 (d, J = 12.3 Hz, 1H), 4.36 (d, J = 12.3 Hz, 1H), 3.90 (s, 3H), 1.31 (s, 9H).

[0082] Depend on Figure 6 It can be seen that the asymmetric sulfidation product H in Example 4... 1 H NMR (400MHz, Chloroform- d ) δ8.24 – 8.16 (m, 2H), 7.56 – 7.49 (m, 2H), 7.50 – 7.41 (m, 3H), 7.44 – 7.35(m, 2H), 7.21 (dd, J = 4.9, 3.0 Hz, 1H), 6.92 (dd, J = 3.0, 1.2 Hz, 1H), 6.78(dd, J = 5.0, 1.3 Hz, 1H), 4.62 (d, J = 12.8 Hz, 1H), 4.35 (d, J = 12.8 Hz, 1H), 1.32 (s, 9H).

[0083] Depend on Figure 7 It can be seen that the asymmetric sulfurization product I of Example 5... 1 H NMR (400MHz, Chloroform- d) δ8.23 – 8.17 (m, 2H), 7.72 – 7.66 (m, 2H), 7.55 – 7.49 (m, 2H), 7.45 – 7.34(m, 3H), 3.22 (tt, J = 11.2, 3.5 Hz, 1H), 2.25 – 2.13 (m, 1H), 1.85 (td, J =15.7, 14.9, 6.3 Hz, 3H), 1.70 – 1.62 (m, 1H), 1.55 (qd, J = 11.9, 3.7 Hz, 1H), 1.40 – 1.33 (m, 1H), 1.33 (s, 9H), 1.33 – 1.18 (m, 3H).

[0084] Depend on Figure 8 It can be seen that the asymmetric sulfurization product J of Example 6 1 H NMR (400MHz, Chloroform- d ) δ8.24 – 8.17 (m, 2H), 7.71 – 7.66 (m, 2H), 7.55 – 7.48 (m, 2H), 7.46 – 7.33(m, 3H), 3.48 (hept, J = 6.9 Hz, 1H), 1.38 (d, J = 6.8 Hz, 3H), 1.32 (s, 9H), 1.25(d, J = 6.7 Hz, 3H).

[0085] Depend on Figure 9 It can be seen that the mixture K containing sulfide products at three sites (α, β, and γ) in Example 7... 1 H NMR (400MHz, Chloroform- d ) δ 8.26 – 8.17 (m, 2H), 7.76 – 7.60 (m, 2H), 7.56 –7.48 (m, 2H), 7.48 – 7.32 (m, 3H), 3.49 (h, J = 6.7 Hz, 0.36H / 1H, β), 3.25 (t, J = 6.9 Hz, 0.26H / 2H, α), 3.12 (p, J= 6.6 Hz, 0.23H / 1H, γ), 2.00 – 1.35 (m,5H), 1.35 – 1.29 (m, 9H), 1.21 – 0.83 (m, 5H).

[0086] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for preparing a chiral thioimine compound, characterized in that, Includes the following steps: Using compounds containing inert carbon-hydrogen bonds and sulfenamide compounds as raw materials, N -[(9 R Using 6′-methoxyoctanol-9-yl]-8-quinoline sulfonamide as a chiral ligand, and fluorobenzene as a solvent, under the action of copper salt and oxidant, and at room temperature and under a protective atmosphere, the chiral ligand forms a copper complex. The copper complex then cleaves the oxidant under visible light irradiation to generate active free radicals. These active free radicals activate inert C-H bonds to generate alkyl free radicals, which react with the sulfonamide in the copper complex, asymmetrically sulfidating the inert C-H bonds to obtain a chiral thioimine compound. The structural formula of the sulfenamide compound is as follows: The oxidant is di-tert-butyl peroxide; the compound containing inert carbon-hydrogen bonds is toluene, xylene, methyl p-methylbenzoate, 3-methylthiophene, cyclohexane, or n-pentane.

2. The method for preparing the chiral thioimine compound according to claim 1, characterized in that, The molar ratio of the sulfenamide compound to the copper salt and the chiral ligand is 1:0.04:0.05, and the molar ratio of the sulfenamide compound to the oxidant is 1:

4.

3. The method for preparing the chiral thioimine compound according to claim 1, characterized in that, The molar ratio of the compound containing inert C-H bonds to the sulfenamide compound is 3~6:0.

1.

4. The method for preparing the chiral thioimine compound according to claim 1, characterized in that, The copper salt is copper tetraacetonitrile hexafluorophosphate.

5. The method for preparing the chiral thioimine compound according to claim 1, characterized in that, The wavelength of the visible light is 455 nm.

6. The method for preparing the chiral thioimine compound according to claim 1, characterized in that, The solvent can be replaced with a mixture of fluorobenzene and acetone.

7. The method for preparing the chiral thioimine compound according to claim 1, characterized in that, After the reaction was completed, the solvent was removed by rotary evaporation under reduced pressure to obtain the initial product. The initial product was then separated by column chromatography using petroleum ether and ethyl acetate to obtain the chiral thioimine compound.

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