Synthetic method of alpha-trifluoromethyl-beta-sulfinyl tertiary alcohol and alpha-trifluoromethyl-beta-thioether tertiary alcohol

Abstract

The invention relates to a synthesis method of alpha-trifluoromethyl-beta-sulfinyl tertiary alcohol and alpha-trifluoromethyl-beta-thioether tertiary alcohol. The invention discloses a selective bifunctionalization method of alpha-(trifluoromethyl) aryl ethylene and a sulfur compound under the photocatalysis of Eosin Y (Eosin Y). According to the method, visible light (30W blue light LED) is taken as an energy source, acetonitrile is taken as a solvent, and the method is carried out at room temperature in an air atmosphere: when a sulfur compound is aromatic thiophenol, alpha-trifluoromethyl-beta-sulfinyl tertiary alcohol (the yield is 51%-92%) is efficiently generated through beta-hydroxyl-sulfinylation reaction; and when the sulfur compound is heterocyclic thiol, alpha-trifluoromethyl-beta-thioether tertiary alcohol (the yield is 74-88%) is selectively generated through beta-hydroxyl-thioetherification reaction. According to the method, a transition metal catalyst is not needed, air is used as an oxidizing agent, atom economy is high, alpha-(trifluoromethyl) aryl ethylene with electron-donating / electron-withdrawing groups, aromatic thiophenol and various heterocyclic mercaptans are covered in a substrate range, products can be further functionalized (such as alkylated), and the method is suitable for industrial production. A green and practical technology is provided for synthesis of functional molecules containing trifluoromethyl and thioether / sulfinyl in pharmaceutical chemistry and material science.

Description

Technical Field

[0001] The present invention relates to the fields of organic synthetic chemistry, medicinal chemistry and materials chemistry, and particularly to a method for selectively synthesizing α-trifluoromethyl-β-sulfinyl tertiary alcohol and α-trifluoromethyl-β-thioether tertiary alcohol by reacting α-(trifluoromethyl)arylethenes with thiophenol or heterocyclic thiol under the photocatalysis of eosin Y. Background Art

[0002] Visible-light photoredox catalysis has become a key paradigm for environmentally friendly organic synthesis, aligning with the core principles of green chemistry (e.g., energy efficiency, minimal waste generation, and reduced use of toxic reagents). The photochemical difunctionalization of olefins is a highly effective strategy for constructing complex molecules, offering high step economies and avoiding harsh reaction conditions and the use of heavy metal catalysts. Among these, the transformation of α-(trifluoromethyl)arylethenes has attracted considerable attention due to the unique properties of the trifluoromethyl group (high electronegativity, metabolic stability, and bioavailability). These compounds are widely found in pharmaceuticals, agrochemicals, and functional materials.

[0003] Despite progress in the difunctionalization of olefins, green synthesis of α-(trifluoromethyl)arylethenes remains challenging. Traditional methods often rely on transition metal catalysts, stoichiometric oxidants, or harsh reaction conditions, contradicting the principles of green chemistry. Furthermore, the strong electron-withdrawing properties of CF3 often promote defluorination side reactions, complicating the controlled construction of multifunctional products.

[0004] Significant progress has been made in the construction of α-trifluoromethyl tertiary alcohols, such as through hydrogen atom transfer (HAT)-mediated transformations and three-component hydroxyl difunctionalization reactions. Lei et al. reported the selective synthesis of β-hydroxysulfoxides / thioethers from 1,1-disubstituted alkenes under different conditions. β-hydroxysulfoxides were obtained under an oxygen atmosphere at room temperature, while β-hydroxythioethers were obtained when triphenylphosphine (PPh3) was added as a reducing agent to dimethyl sulfoxide (DMSO). However, this study did not involve heterocyclic thiols.

[0005] In view of this, it is of great significance to develop a green, efficient and highly selective β-hydroxy-sulfenylation / thioetherification method for α-(trifluoromethyl)arylethylene. Summary of the Invention

[0006] In view of the problems existing in the prior art of the difunctionalization reaction of α-(trifluoromethyl)arylethenes, such as dependence on transition metal catalysts, harsh reaction conditions, poor chemical selectivity and limited substrate range, the present invention provides a method for photocatalysis using Eosin Y to efficiently and selectively synthesize α-trifluoromethyl-β-sulfinyl tertiary alcohols and α-trifluoromethyl-β-thioether tertiary alcohols under mild conditions.

[0007] The present invention discloses a method for synthesizing α-trifluoromethyl-β-sulfinyl tertiary alcohol and α-trifluoromethyl-β-thioether tertiary alcohol. The method comprises the following steps: under visible light irradiation, using eosin Y as a photocatalyst, reacting α-(trifluoromethyl)arylethene with a sulfur compound in acetonitrile under air atmosphere at room temperature. When the sulfur compound is an aromatic thiol, the α-trifluoromethyl-β-sulfinyl tertiary alcohol is generated through a β-hydroxy-sulfinylation reaction; and when the sulfur compound is a heterocyclic thiol, the α-trifluoromethyl-β-thioether tertiary alcohol is selectively generated through a β-hydroxy-thioetherification reaction.

[0008] The general reaction formula is as follows:

[0009] Among them: the aryl (Ar) part of α-(trifluoromethyl)arylethylene can carry an electron-donating group (such as -CH3, -OCH3, -tBu), an electron-withdrawing group (such as -F, -Cl, -Br, -NO2, -CN) or a naphthyl group; the aryl (Ar¢) of aromatic thiophenol (Ar¢-SH) can carry an electron-donating group (such as -CH3, -OCH3, -iPr, -tBu), an electron-withdrawing group (such as -F, -Cl, -Br) or a hydroxyl group; heterocyclic thiols (Het-SH) include 1-methyl-1H-tetrazole-5-thiol, benzothiazole thiols, benzoxazole thiols, 1,2,4-thiadiazole thiols, etc.

[0010] Beneficial effects: (1) Green and environmentally friendly: using visible light (blue LED) as the energy source and Eosin Y as the photocatalyst, without the need for transition metals and air as the oxidant, which is in line with the concept of green chemistry; (2) Mild reaction conditions: the reaction is carried out at room temperature and in air atmosphere, without the need for high temperature, high pressure or inert gas protection; (3) High chemical selectivity: selectively generating sulfinyl or sulfide products according to the type of sulfur source (aromatic thiol / heterocyclic thiol); (4) Wide substrate range: applicable to a variety of substituted α-(trifluoromethyl)arylethylenes, aromatic thiol and heterocyclic thiol, with good functional group compatibility; (5) High atom economy: the reaction effectively integrates the sulfur source and oxygen in the air (as a sulfoxide oxygen source) into the product; (6) High practicality: gram-scale preparation is possible, and the product can be further functionalized (such as alkylation), with potential application value in drug and material synthesis. DETAILED DESCRIPTION

[0011] The following examples are used to illustrate the present invention in detail, but do not limit the scope of protection of the present invention.

[0012] To a dried 25 mL stoppered test tube, add α-(trifluoromethyl)styrene (0.5 mmol), p-toluenethiophenol (1.0 mmol), Eosin Y (2.0 mol%), and anhydrous acetonitrile (2 mL). Seal the tube with a rubber stopper. Place the tube under a 30 W blue LED light (3.5-4 cm from the light source) and stir at room temperature for 24 hours. Reaction progress is monitored by TLC. After completion of the reaction, extract with ethyl acetate (15 mL). The organic phase is washed three times with water. The combined organic layers are dried over anhydrous Na₂SO₄ and concentrated under reduced pressure on a rotary evaporator. The residue is purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 7:1, v / v) to obtain the product as a white solid in 87% yield (dr = 52:48).

[0013] Structural characterization data: melting point: 96-98 ° C; ¹H NMR (400 MHz, CDCl3) δ 7.65 (d, J=8.5Hz, 1H), 7.54-7.50 (m, 1H), 7.50-7.44 (m, 2H), 7.41 (d, J=8.7 Hz, 1H), 7.36(d, J=7.9 Hz, 1H), 7.30-7.24 (m, 2H), 6.60 (s, 0.40H major isomer), 6.06 (s,0.39H minor isomer), 3.51-3.32 (m, 1.02H major isomer), 3.09 (dt, J=14.0, 1.2Hz, 0.95H minor isomer), 2.42 (s, 1.45H minor isomer), 2.40 (s, 1.55H majorisomer);¹³C NMR (101 MHz, CDCl3) δ 143.40, 143.08, 138.94, 138.90, 135.82,135.15, 134.23, 130.64, 130.48, 129.13, 128.91, 128.66, 127.35, 124.6 (m(CF), J=252.5 Hz), 124.24, 124.06, 77.84 (m, J=30.3 Hz), 59.33, 58.13, 21.66,21.60;¹ 9 F NMR (376 MHz, CDCl3) δ -76.76, -80.76; HRMS (ESI): m / z calcd. forC 16 H 15F3O2SNa⁺ [M+Na]⁺ 351.0641; found 351.0646.

[0014] The reaction apparatus and operating procedures of Example 1 were used, except that 1-methyl-1H-tetrazole-5-thiol (1.0 mmol) was used instead of p-toluene thiophenol. Other reaction conditions (catalyst amount, solvent, light source, temperature, and time) remained unchanged. After completion of the reaction, the product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 5:1, v / v) to obtain a white solid product in a yield of 88%. Structural characterization data: melting point: 55-57°C; ¹H NMR (400 MHz, CDCl3) δ 7.57-7.47 (m, 2H), 7.41-7.29 (m, 3H), 5.89 (s, 1H), 4.06 (d, J=15.1 Hz, 1H), 3.89 (d, J=15.1 Hz,1H), 3.77 (s, 3H); ¹³C NMR (101 MHz, CDCl3) δ 155.20, 135.72, 129.19, 128.65,126.78, 125.04 (q(CF), J=288.9 Hz), 77.35 (q, J=28.3 Hz), 39.68, 33.87; ¹ 9 FNMR (376 MHz, CDCl3) δ -77.51; HRMS (ESI): m / z calcd. for C 11 H 11 F3N4OSNa⁺ [M+Na]⁺ 327.0503; found 327.0501.

[0015] The method of Example 1 was used, except that 4-tert-butylthiophenol (1.0 mmol) was used instead of p-toluenethiophenol. The silica gel column chromatography eluent was adjusted to petroleum ether / ethyl acetate = 8:1 (v / v) to obtain a white solid product with a yield of 92% (dr = 70:30). Structural characterization data: melting point: 73-75 ° C; ¹H NMR (400 MHz, DMSO-d6) δ 7.66 (td, J=7.3,6.4, 1.8 Hz, 2H), 7.62 (s, 1H), 7.57-7.46 (m, 3H), 7.40 (dt, J=4.5, 2.5 Hz,3H), 7.21 (d, J=1.5 Hz, 1H), 3.87 (d, J=13.7 Hz, 0.70H major isomer), 3.80(d, J=13.8 Hz, 0.30H minor isomer), 3.48 (dd, J=13.8, 10.8 Hz, 2H isomersmixture), 1.30 (d, J=2.7 Hz, 2.95H minor isomer), 1.29 (s, 6.07H majorisomer);¹³C NMR (101 MHz, DMSO-d6) δ 154.60, 154.37, 142.51, 141.86, 136.45,135.94, 129.33, 129.07, 128.76, 128.35, 127.68, 127.54, 126.75, 126.72,124.75, 124.60, 124.53, 75.99 (m, J=29.3 Hz), 64.39, 63.41, 35.21, 31.47;¹ 9 FNMR (376 MHz, DMSO-d6) δ -78.39, -78.51; HRMS (ESI): m / z calcd. forC 19 H 21 F3O2SNa⁺ [M+Na]⁺ 393.1112; found 393.1110.

[0016] The reaction system of Example 1 was used, except that p-toluene thiophenol was replaced with benzo[d]thiazole-2-thiol (1.0 mmol). After the reaction, the product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 6:1, v / v) to obtain a white solid product in a yield of 77%. Structural characterization data: melting point: 123-125℃; ¹H NMR (400 MHz, CDCl3) δ 7.87-7.81 (m, 1H), 7.68-7.63 (m, 1H), 7.56 (dd, J=7.5, 1.5 Hz, 2H), 7.42-7.33 (m, 3H),7.33-7.25 (m, 2H), 4.19 (d, J=15.2 Hz, 1H), 3.76 (d, J=15.2 Hz, 1H); ¹³C NMR (101 MHz, CDCl3) δ 166.23, 152.31, 135.97, 134.78, 128.94, 128.25, 126.93,126.57, 125.43 (q(CF), J=288.9 Hz), 124.75, 121.96, 121.23, 77.68 (q, J=28.3Hz), 38.60;¹ 9 F NMR (376 MHz, CDCl3) δ -77.60; HRMS (ESI): m / z calcd. forC 16 H 13 F3NOS2⁺ [M+H]⁺ 356.0391; found 356.0397.

[0017] To a dried 100 mL three-necked flask, α-(trifluoromethyl)styrene (5 mmol), p-toluenethiophenol (10 mmol), Eosin Y (2.0 mol%), and anhydrous acetonitrile (20 mL) were added. A reflux condenser was installed at the flask neck. The reaction was stirred at room temperature for 24 hours under irradiation with a 30 W blue LED lamp (the light source was 4 cm away from the flask). After completion of the reaction, saturated NaCl solution (50 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (50 mL x 3). The combined organic phases were dried over anhydrous NaSO, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 7:1, v / v) to obtain a white solid product in a 71% yield (1.16 g). The structural characterization data were consistent with those in Example 1.

[0018] The product prepared by β-hydroxysulfinylation in Example 1 (0.25 mmol) was dissolved in anhydrous acetonitrile (2 mL). Potassium carbonate (0.5 mmol) and iodomethane (0.3 mmol) were added and stirred at room temperature for 6 hours. After the reaction, the inorganic salts were removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1, v / v) to obtain the alkylated product (α-methoxy-α-trifluoromethyl-β-toluenesulfinylpropylbenzene) in a 90% yield. Key structural data: ¹H NMR (400 MHz, CDCl3) δ 7.62-7.58 (m, 2H), 7.48-7.32 (m, 5H), 7.21 (d, J=8.0 Hz, 2H), 3.52 (s, 3H), 3.48 (d, J=13.8 Hz, 1H), 3.21 (d, J=13.8 Hz, 1H), 2.40 (s, 3H); HRMS (ESI): m / z calcd. for C 17 H 17 F3O2SNa⁺ [M+Na]⁺ 365.0798; found365.0801.

[0019] The operating procedure of Example 1 was adopted, except that o-toluenethiophenol (1.0 mmol) was used instead of p-toluenethiophenol, and the silica gel column chromatography eluent was petroleum ether / ethyl acetate = 7:1 (v / v) to obtain a white solid product with a yield of 72% (dr = 60:40). Structural characterization data: melting point: 84-86°C; ¹H NMR (400 MHz, DMSO-d6) δ 7.87-7.77 (m, 1H), 7.67 (dq, J=5.7, 2.2, 1.6 Hz, 2H), 7.52-7.29 (m, 6H), 7.24-7.21 (m, 1H), 3.80 (d, J=13.8 Hz, 0.60H major isomer), 3.60 (d, J=14.0 Hz, 0.40H minor isomer),3.53-3.35 (m, 2H isomers mixture), 2.35 (s, 1.25H minor isomer), 2.08 (s,1.75H major isomer); ¹³C NMR (101 MHz, DMSO-d6) δ 144.06, 143.55, 136.64,136.43, 135.39, 135.19, 131.61, 131.45, 131.30, 131.23, 129.43, 129.17,128.77, 128.41, 127.65, 127.63, 127.35, 125.42 (m(CF), J=252.5 Hz), 124.48,124.43, 75.92 (m, J=29.3 Hz), 63.46, 62.93, 18.30, 18.08;¹ 9 F NMR (376 MHz, DMSO-d6) δ -78.42, -78.47; HRMS (ESI): m / z calcd. for C 16 H 15 F3O2SNa⁺ [M+Na]⁺351.0643; found 351.0646.

[0020] The reaction conditions of Example 1 were adopted, except that p-thiocresol was replaced by m-thiocresol (1.0 mmol) and the purification eluent was petroleum ether / ethyl acetate = 7:1 (v / v). A colorless oily product was obtained with a yield of 78% (dr = 70:30). Structural characterization data: ¹H NMR (400 MHz, DMSO-d6) δ 7.71-7.63 (m, 2H), 7.53-7.40 (m, 5H), 7.38-7.32 (m, 2H), 7.23 (d, J=17.4 Hz, 1H), 3.87 (d, J=13.7 Hz, 0.70H majorisomer), 3.81 (d, J=13.9 Hz, 0.30H minor isomer), 3.47 (dd, J=13.8, 9.3 Hz,2H isomers mixture), 2.39 (s, 2.0H minor isomer), 2.34 (s, 4.0H majorisomer); ¹³C NMR (101 MHz, DMSO-d6) δ 145.53, 144.94, 139.54, 139.50, 136.46,135.88, 132.35, 132.16, 130.38, 129.83, 129.71, 129.68, 129.39, 129.09,128.87, 128.78, 128.34, 127.71, 127.59, 125.22 (m(CF), J=255.5 Hz), 124.91,124.82, 121.79, 121.66, 75.51 (m, J=30.3 Hz), 64.44, 63.57, 21.51, 21.43;¹ 9 FNMR (376 MHz, DMSO-d6) δ -78.25, -78.36; HRMS (ESI): m / z calcd. forC 16 H 15 F3O2SNa⁺ [M+Na]⁺ 351.0643; found 351.0646.

[0021] The method of Example 1 was used, except that 4-methoxythiophenol (1.0 mmol) was used instead of p-toluenethiophenol. The silica gel column chromatography eluent was petroleum ether / ethyl acetate = 6:1 (v / v). A white solid product was obtained with a yield of 91% (dr = 70:30). Structural characterization data: melting point: 93-95°C; ¹H NMR (400 MHz, DMSO-d6) δ 7.69-7.63 (m, 2H), 7.63-7.49 (m, 2H), 7.44-7.39 (m, 3H), 7.28 (s, 0.3H minor isomer), 7.17 (s,0.7H major isomer), 7.16-7.04 (m, 2H), 3.88-3.77 (m, 4H), 3.46 (dd, J=14.8,13.7 Hz, 1H); ¹³C NMR (101 MHz, DMSO-d6) δ 148.14, 147.93, 147.86, 147.46,142.47, 141.80, 141.74, 141.47, 130.33, 130.27, 129.93, 129.57, 128.42,125.53 (m(CF), J=184.8 Hz), 124.83, 124.73, 124.62, 123.59, 121.53, 108.35,108.10, 101.92, 101.79, 75.90 (m, J=29.3 Hz), 64.40, 62.95, 21.41;¹ 9 F NMR (376 MHz, DMSO-d6) δ -78.32, -78.36; HRMS (ESI): m / z calcd. for C 16 H 15 F3O3SNa⁺[M+Na]⁺ 367.0592; found 367.0591.

[0022] The reaction system of Example 1 was used, 4-fluorobenzenethiol (1.0 mmol) was used instead of p-toluenethiophenol, and the purification eluent was petroleum ether / ethyl acetate = 7:1 (v / v) to obtain a white solid product with a yield of 82% (dr = 56:44). Structural characterization data: melting point: 101-103 ° C; ¹H NMR (400 MHz, DMSO-d6) δ 7.76-7.70 (m, 1H), 7.70-7.60 (m, 3H), 7.49-7.45 (m, 1H), 7.45-7.39 (m, 3H), 7.39-7.33 (m, 1.49H isomersmixture), 7.25 (s, 0.57H major isomer), 3.92 (d, J=13.8 Hz, 0.56H majorisomer), 3.87 (d, J=13.8 Hz, 0.44H minor isomer), 3.53 (d, J=13.7 Hz, 0.56Hmajor isomer), 3.48 (d, J=13.8 Hz, 0.43H minor isomer);¹³C NMR (101 MHz, DMSO-d6) δ 164.15 (q, J=249.5 Hz), 141.37, 141.34, 140.84, 140.81, 136.36,135.82, 129.35, 129.13, 128.77, 128.38, 127.69, 127.58, 127.54, 127.49,127.41, 125.33 (m, J=252.5 Hz), 117.12, 117.07, 116.89, 116.85, 75.59 (m, J=29.3 Hz), 64.38, 63.59;¹ 9 F NMR (376 MHz, DMSO-d6) δ -78.26, -78.44, -109.19, -109.21, -109.23, -109.24, -109.27, -109.60, -109.63, -109.64, -109.66, -109.68; HRMS (ESI): m / z calcd. for C 15 H 12 F4O2SNa⁺ [M+Na]⁺ 355.0392; found355.0392.

[0023] The operating procedure of Example 1 was adopted, except that benzo[d]oxazole-2-thiol (1.0 mmol) was used instead of p-toluene thiophenol, and the silica gel column chromatography eluent was petroleum ether / ethyl acetate = 6:1 (v / v) to obtain a white solid product with a yield of 80%. Structural characterization data: melting point: 122-124 ° C; ¹H NMR (400 MHz, CDCl3) δ 7.58-7.51 (m, 3H), 7.41-7.29 (m, 4H), 7.29-7.19 (m, 2H), 6.99 (s, 1H), 4.14 (d, J=15.3 Hz, 1H), 3.77 (d, J=15.2 Hz, 1H); ¹³C NMR (101 MHz, CDCl3) δ 182.93, 181.90, 167.08, 152.34,140.19, 136.35, 129.01, 126.92, 126.71, 125.28 (q(CF), J=288.9 Hz), 125.07,124.85, 118.42, 110.39, 77.94 (q, J=28.3 Hz), 38.73;¹ 9 F NMR (376 MHz, CDCl3)δ-77.58; HRMS (ESI): m / z calcd. for C 16 H 13 F3NO2S⁺ [M+H]⁺ 340.0619; found340.0619.

[0024] The reaction conditions of Example 1 were adopted, 1,2,4-thiadiazole-5-thiol (1.0 mmol) was used instead of p-toluene thiophenol, and the purification eluent was petroleum ether / ethyl acetate = 5:1 (v / v), to obtain a white solid product with a yield of 84%. Structural characterization data: melting point: 118-120℃; ¹H NMR (400 MHz, CDCl3) δ 8.94 (s, 1H), 7.64-7.49 (m, 2H),7.45-7.28 (m, 3H), 6.40 (s, 1H), 4.20 (d, J=15.2 Hz, 1H), 3.85 (d, J=15.1 Hz,1H); ¹³C NMR (101 MHz, CDCl3) δ 167.87, 152.60, 147.35, 136.37, 129.02,128.57, 126.88, 125.25 (q(CF), J=288.9 Hz), 77.71, 77.35, 40.46;¹ 9F NMR (376MHz, CDCl3) δ -77.55; HRMS (ESI): m / z calcd. for C 11 H9F3N2OS2Na⁺ [M+Na]⁺329.0006; found 329.0003.

[0025] The method of Example 1 was used, using 3-methoxy-α-(trifluoromethyl)styrene (0.5 mmol) and 1-methyl-1H-tetrazole-5-thiol (1.0 mmol) as raw materials, and silica gel column chromatography with petroleum ether / ethyl acetate = 5:1 (v / v) as the eluent to obtain a white solid product in a yield of 83%. Structural characterization data: melting point: 90-92°C; ¹H NMR (400 MHz, CDCl3) δ 7.26 (t, J=8.0 Hz, 1H), 7.14 (t, J=2.2 Hz, 1H), 7.04 (ddt, J=7.9,1.9, 0.9 Hz, 1H), 6.86 (ddd, J=8.2, 2.6, 0.9 Hz, 1H), 5.93 (s, 1H), 4.04 (d,J=15.1 Hz, 1H), 3.86 (d, J=15.1 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H); ¹³C NMR (101 MHz, CDCl3) δ 159.84, 155.26, 137.43, 129.65, 124.98 (q(CF), J=288.9Hz), 118.71, 114.45, 113.06, 77.73, 77.32, 55.43, 39.73, 33.88;¹ 9 F NMR (376MHz, CDCl3) δ -78.76; HRMS (ESI): m / z calcd. for C 12 H 14 F3N4OS⁺ [M+H]⁺ 335.0790; found 335.0785.

[0026] The reaction system of Example 1 was used, with 4-methoxy-α-(trifluoromethyl)styrene (0.5 mmol) and 1-methyl-1H-tetrazole-5-thiol (1.0 mmol) as raw materials, and the purification eluent was petroleum ether / ethyl acetate = 5:1 (v / v). A white solid product was obtained with a yield of 89%. Structural characterization data: melting point: 105-107 ° C; ¹H NMR (400 MHz, CDCl3) δ7.50 (d, J=8.8 Hz, 2H), 6.96-6.90 (m, 2H), 4.10 (d, J=15.1 Hz, 1H), 3.93 (d,J=15.0 Hz, 1H), 3.84 (s, 3H), 3.82 (s, 3H); ¹³C NMR (101 MHz, CDCl3) δ 159.10,154.18, 127.11, 126.55, 124.10 (q(CF), J=288.9 Hz), 112.92, 76.13 (q, J=28.3Hz), 54.37, 38.77, 32.83;¹ 9 F NMR (376 MHz, CDCl3) δ -78.78; HRMS (ESI): m / zcalcd. for C 12 H 14 F3N4OS⁺ [M+H]⁺ 335.0790; found 335.0780.

[0027] To a dried, stoppered 25 mL test tube, α-(trifluoromethyl)styrene (0.5 mmol), p-toluenethiophenol (1.0 mmol), Eosin Y (2.0 mol%), and anhydrous DMSO (2 mL) were added. PPh3 (0.6 mmol) was added as a reducing agent. The tube was sealed and reacted at room temperature under a 30 W blue LED lamp for 2 hours. After completion of the reaction, the mixture was extracted with ethyl acetate, washed with water, and the organic phase was dried, concentrated, and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10:1, v / v) to obtain the product as a colorless oil in a 64% yield. Structural characterization data: ¹H NMR (400 MHz, CDCl3) δ 7.52 (dd, J=6.7, 3.0 Hz, 2H), 7.37-7.30 (m, 3H), 7.23-7.16 (m, 2H), 7.03 (d, J=7.9 Hz, 2H), 3.74 (d, J=13.9Hz, 1H), 3.65 (d, J=13.9 Hz, 2H), 2.29 (s, 3H); ¹³C NMR (101 MHz, CDCl3) δ 137.80, 136.40, 131.65, 131.16, 130.05, 128.94, 128.42, 126.70, 124.89 (q(CF), J=287.9 ​​Hz), 75.95 (q, J=29.3 Hz), 43.38, 21.13;¹ 9 F NMR (376 MHz, CDCl3) δ-79.15; GC-MS (EI): m / z calcd. 312.0; found 312.0.

[0028] The operating procedure of Example 1 was adopted, using 4-chloro-α-(trifluoromethyl)styrene (0.5 mmol) and p-toluene thiophenol (1.0 mmol) as raw materials, and the eluent for silica gel column chromatography was petroleum ether / ethyl acetate = 8:1 (v / v). A colorless oily product was obtained with a yield of 86% (dr = 51:49). Structural characterization data: ¹H NMR (400 MHz, CDCl3) δ 7.66 (d, J=8.5Hz, 1H), 7.56-7.51 (m, 1H), 7.51-7.46 (m, 2H), 7.46-7.41 (m, 1H), 7.37 (d, J=7.9 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.29-7.26 (m, 1H), 6.61 (s, 0.40H minorisomer), 6.07 (s, 0.40H major isomer), 3.48-3.41 (m, 1H), 3.39 (d, J=13.3 Hz,0.49H major isomer), 3.10 (dt, J=14.0, 1.2 Hz, 0.49H minor isomer), 2.44 (s, 1.48H minor isomer), 2.41 (s, 1.52H major isomer); ¹³C NMR (101 MHz, CDCl3) δ143.40, 143.08, 138.94, 138.90, 135.82, 135.15, 134.23, 130.64, 130.48,129.13, 128.91, 128.66, 127.35, 124.25 (m(CF), J=158.6 Hz), 124.24, 124.06,77.15 (m, J=31.3 Hz), 59.33, 58.13, 21.66, 21.60;¹ 9 F NMR (376 MHz, CDCl3) δ -76.94, -80.91; HRMS (ESI): m / z calcd. for C 16 H 15 ClF3O2S⁺ [M+H]⁺ 363.0404; found363.0404.

[0029] Using the reaction conditions of Example 1, 2-(trifluoromethyl)naphthylethylene (0.0 mol) and p-toluenethiophenol (1.0 mmol) were used as raw materials, and the eluent was petroleum ether / ethyl acetate = 7:1 (v / v). A white solid product was obtained in an 88% yield (dr = 73:27). Structural characterization data: melting point: 123-125°C; ¹H NMR (400 MHz, DMSO-d6) δ 8.29-8.22 (m, 1H), 8.03-7.91 (m, 3H), 7.79-7.70 (m, 1H), 7.64-7.53(m, 3H), 7.48-7.39 (m, 2H), 7.38-7.24 (m, 2H), 3.99 (d, J=13.7 Hz, 0.72H major isomer), 3.94 (d, J=13.8 Hz, 0.29H minor isomer), 3.58 (d, J=13.7 Hz,0.73H major isomer), 3.52 (d, J=13.8 Hz, 0.26H minor isomer), 2.37 (s, 0.8H minor isomer), 2.28 (s, 2.2H major isomer); ¹³C NMR (101 MHz, DMSO-d6) δ144.06, 143.55, 136.64, 136.43, 135.39, 135.19, 131.61, 131.45, 131.30,131.23, 129.43, 129.17, 128.77, 128.41, 127.65, 127.63, 127.35, 127.03,126.67, 125.12 (m(CF), J=252.3 Hz), 124.48, 124.43, 124.17, 123.81, 76.12(m, J=29.3 Hz), 63.46, 62.93, 18.30, 18.08;¹ 9 F NMR (376 MHz, DMSO-d6) δ -78.04; HRMS (ESI): m / z calcd. for C 20 H 17 F3O2SNa⁺ [M+Na]⁺ 410.0799; found410.0799.

Claims

1. A method for synthesizing α-trifluoromethyl-β-sulfinyl tertiary alcohol or α-trifluoromethyl-β-thioether tertiary alcohol, characterized in that: Under the photocatalysis of Eosin Y, α-(trifluoromethyl)arylethene reacts with a sulfur compound in acetonitrile under irradiation of a blue LED lamp, an air atmosphere, and room temperature. When the sulfur compound is an aromatic thiol, α-trifluoromethyl-β-sulfinyl tertiary alcohol is generated; when the sulfur compound is a heterocyclic thiol, α-trifluoromethyl-β-thioether tertiary alcohol is generated.

2. The method according to claim 1, characterized in that The aryl group of the α-(trifluoromethyl)arylethylene is phenyl, substituted phenyl or naphthalene-2-yl; the substituent of the substituted phenyl is selected from methyl, ethyl, methoxy, fluorine, chlorine, bromine, nitro or cyano.

3. The method according to claim 1, characterized in that The aromatic thiophenol is thiophenol or substituted thiophenol; the substituent of the substituted thiophenol is selected from methyl, methoxy, isopropyl, tert-butyl, fluorine, chlorine, bromine or hydroxyl.

4. The method according to claim 1, wherein The heterocyclic thiol is selected from 1-methyl-1H-tetrazole-5-thiol, benzo[d]oxazole-2-thiol, benzo[d]thiazole-2-thiol or 1,2,4-thiadiazole-5-thiol.

Images