Preparation method and application of a gem-di(trifluoromethyl) dihydrothiopyran

Abstract

The application discloses a novel geminal di(trifluoromethyl) dihydrothiopyran antitumor compound and a rapid synthesis method thereof, and belongs to the field of medicinal chemistry. Since the efficient construction of geminal di(trifluoromethyl) dihydrothiopyran still has problems such as complicated method and less related research, the application solves the problems well. The method directly constructs the geminal di(trifluoromethyl) dihydrothiopyran by taking a conjugated diene as a substrate, taking triphenylphosphine as a reducing agent, taking hexafluoroacetone trihydrate as a stable fluorine source, taking thionyl chloride as a sulfur source, and taking magnesium oxide as an activating agent. The method has the advantages of simple operation, high reaction yield, wide substrate application range and mild conditions, and thus has broad application prospects in the fields of drug molecular structure modification, functional material development and fine chemical product synthesis.

Description

Technical Field

[0001] This invention relates to the field of medicinal chemistry, specifically to a novel gem-bis(trifluoromethyl)dihydrothiapyran antitumor compound and its rapid synthesis method. Background Technology

[0002] In medicinal chemistry, the unique electronic and steric effects of the gem-bis(trifluoromethyl)dihydrothiapyran gene have important application prospects in drug molecule design. It can not only provide key intermediates for novel thiofluorine drugs, but also provide new ideas for the design and synthesis of functional molecules, and play a positive role in promoting the development of medicinal chemistry and materials science.

[0003] Currently, hexafluoroisopropylation reactions suffer from limitations such as a single reaction mode and limited substrate applicability. Therefore, developing an efficient and mild multi-component hexafluoroisopropylation reaction system is of great significance. Summary of the Invention

[0004] The purpose of this invention is to address the limitations of current methods for introducing hexafluoroisopropyl fragments, such as single reaction mode and narrow reaction substrate range, and to provide an efficient, mild, and low-cost method for introducing hexafluoroisopropyl fragments, which has successfully achieved the efficient construction of gem-bis(trifluoromethyl)dihydrothiapyran compounds.

[0005] The technical solution of this invention is: a rapid synthesis method for gem-bis(trifluoromethyl)dihydrothiapyran compounds, comprising the following steps: under anhydrous and oxygen-free conditions, a sulfur source, a reducing agent, and a hexafluoroisopropylating agent are dissolved in an anhydrous solvent, and the system is activated at room temperature to generate a hexafluoroisopropyl polysulfide intermediate; then, an activator and a substrate conjugated diene are added and stirred at high speed, and the hexafluoroisopropyl polysulfide is dehydrated under the action of the activator to obtain the intermediate, which undergoes a Diels-Alder reaction with the conjugated diene to obtain the product gem-bis(trifluoromethyl)dihydrothiapyran compound.

[0006] The hexafluoroisopropylating agent is hexafluoroacetone trihydrate.

[0007] The sulfur source is thionyl chloride.

[0008] The reducing agent is triphenylphosphine.

[0009] The anhydrous solvents include: 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, carbon tetrachloride, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, and toluene.

[0010] The catalysts include: magnesium oxide, calcium oxide, aluminum oxide, silicon dioxide, phosphorus pentoxide, magnesium sulfate, and magnesium chloride.

[0011] The conjugated dienes include terminal olefins and non-terminal olefins.

[0012] The preferred conditions for the stirring reaction are stirring at 110°C for 12 hours.

[0013] The aforementioned gem-bis(trifluoromethyl)dihydrothiapyran compound has the structure shown in Formula I: , Formula I In Formula I, R1 and R2 are the same group, which are aryl, naphthyl, or thiophene.

[0014] The beneficial effects of this invention are: simple and efficient reaction, mild conditions, low cost, and wide applicability. It can efficiently achieve late-stage fluorination modification of bioactive molecules, which is helpful for the development of innovative fluorine-containing drugs. It holds promise as a lead compound for anti-tumor drugs. Detailed Implementation

[0015] The following examples further illustrate the outstanding features and significant advancements of the present invention, but are for illustrative purposes only and do not limit the scope of the invention.

[0016] Example 1 Preparation of 4,5-diphenyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 1,3-butadienediyl-2,3-diyldiphenyl (0.0206 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-diphenyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 1, with a yield of 99%.

[0017] 1 H NMR (400 MHz, CDCl3) δ 7.24 – 7.17 (m, 6H), 7.08 (dd, J = 7.5, 2.1Hz, 4H), 3.65 (s, 2H), 3.16 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -73.53 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 140.52, 140.25, 137.48, 133.75, 129.06,128.70, 128.26 (d, J = 19.7 Hz), 127.21 (d, J = 11.4 Hz), 125.79, 123.90 (d,J = 2.1 Hz), 60.12 (p, J = 26.4 Hz), 32.87 (t, J = 1.9 Hz), 31.69. HRMS-ESI m / z : [M+Na]+ calcd for C19H14F6NaS+ 411.0613, found 411.0459 , Formula 1.

[0018] Example 2 Preparation of 4,5-bis(p-tolyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(methylbenzene) (0.0234 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(p-tolyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 2, with a yield of 99%.

[0019] 1 H NMR (600 MHz, CDCl3) δ 6.91 (t, J = 8.7 Hz, 4H), 6.87 – 6.84 (m,4H), 3.49 (s, 2H), 3.01 (s, 2H), 2.20 (d, J = 3.8 Hz, 6H). 19 F NMR (565 MHz, CDCl3) δ -73.52 (s, 6F) 13 C NMR (152 MHz, CDCl3) δ 140.52, 140.25, 137.48, 133.75, 129.06,128.70, 128.26 (d, J = 19.7 Hz), 127.21 (d, J = 11.4 Hz), 125.79 - 122.03(m), 60.47 - 59.77(m), 32.87 (t, J = 1.9 Hz), 31.69. HRMS-ESI m / z: [M+Na]+ calcd forC21H18F6NaS+ 439.0926, found439.0941. , Equation 2.

[0020] Example 3 Preparation of 4,5-bis(4-isopropylphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(isopropylbenzene) (0.029 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-isopropylphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 3, with a yield of 99%.

[0021] 1H NMR (600 MHz, CDCl3) δ 6.95 (t, J = 8.4 Hz, 4H), 6.88 (dd, J =8.4, 2.5 Hz, 4H), 3.50 (s, 2H), 3.02 (s, 2H), 2.75 (pd, J = 6.9, 3.7 Hz, 2H),1.12 (dd, J = 7.0, 0.9 Hz, 12H). 19 F NMR (565 MHz, CDCl3) δ -73.47 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 147.71 (d, J = 16.5 Hz), 137.95, 137.72,136.74, 133.19, 128.91, 128.62, 126.5 – 121.0 (m), 60.78 – 59.67 (m), 33.68(d, J = 9.0 Hz), 32.99, 31.78, 23.84 (d, J = 4.3 Hz). HRMS-ESI m / z : [M+H]+ calcd for C25H27F6S+ 473.1732, found 473.1736. , Formula 3.

[0022] Example 4 Preparation of 4,5-bis(4-tert-butylphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(tert-butylbenzene) (0.0318 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-tert-butylphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 4, with a yield of 99%.

[0023] 1 H NMR (400 MHz, CDCl3) δ 7.22 (dd, J = 8.3, 5.9 Hz, 4H), 7.01 (dd, J= 8.5, 2.8 Hz, 4H), 3.62 (s, 2H), 3.14 (s, 2H), 1.30 (d, J = 1.2 Hz, 18H). 19 F NMR (376 MHz, CDCl3) δ -73.49 (s, 6F).. 13 C NMR (152 MHz, CDCl3) δ 150.01 (d, J = 13.5 Hz), 137.56, 137.33,136.68, 133.19, 128.51 (d, J = 41.8 Hz), 125.02 (d, J = 15.4 Hz), 60.57 –59.57 (m), 34.47 (d, J = 5.7 Hz), 32.98, 31.74, 31.24. HRMS-ESI m / z : [M+H]+ calcd for C27H31F6S+ 501.2045, found 501.2041. , Formula 4.

[0024] Example 5 Preparation of 4,5-bis(4-methoxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(methoxybenzene) (0.0266 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-methoxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 5, with a yield of 99%.

[0025] 1 H NMR (400 MHz, CDCl3) δ 6.99 (d, J = 8.3 Hz, 4H), 6.82 – 6.58 (m,4H), 3.78 (s, 6H), 3.59 (s, 2H), 3.10 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.52 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 157.46 (d, J = 12.6 Hz), 135.05, 132.00,131.67, 131.37, 129.17, 128.86, 112.63 (d, J = 21.2 Hz), 59.20 (t, J = 26.3Hz), 54.13 (d, J = 6.0 Hz), 31.97, 30.80. HRMS-ESI m / z : [M+H]+ calcd for C21H19F6O2S+ 449.1004, found 449.1008 , Formula 5.

[0026] Example 6 Preparation of 4,5-bis(4-ethoxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(ethoxybenzene) (0.0294 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-ethoxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 6, with a yield of 99%.

[0027] 1 H NMR (400 MHz, CDCl3) δ 7.02 – 6.94 (m, 4H), 6.80 – 6.67 (m, 4H), 3.99 (q, J = 7.0 Hz, 4H), 3.58 (s, 2H), 3.10 (s, 2H), 1.41 (t, J = 7.0 Hz,6H). 19 F NMR (376 MHz, CDCl3) δ -73.52 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 157.87 (d, J = 10.9 Hz), 136.03, 132.89,132.57, 132.36, 130.19, 129.87, 127.38 - 121.14 (m), 114.16 (d, J = 23.5 Hz), 63.33 (d, J = 7.2 Hz), 61.32 – 59.48 (m), 33.00, 31.82, 14.81 (d, J = 2.3Hz). HRMS-ESI m / z : [M+H]+ calcd for C23H23F6O2S+ 477.1317, found477.1328. , Formula 6.

[0028] Example 7 Preparation of 4,5-bis(4-benzyloxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis((benzyloxy)benzene) (0.0418 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-benzyloxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 7, with a yield of 99%.

[0029] 1 H NMR (400 MHz, CDCl3) δ 7.46 – 7.35 (m, 10H), 7.00 (dd, J = 8.7,1.7 Hz, 4H), 6.87 – 6.78 (m, 4H), 5.03 (d, J = 2.1 Hz, 4H), 3.58 (s, 2H),3.10 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.52(s, 6F). 13C NMR (152 MHz, CDCl3) δ 135.78 (d, J = 4.2 Hz), 135.09, 132.24,131.92, 131.42, 129.05 (d, J = 48.6 Hz), 127.56, 127.26, 127.00, 126.49 (d, J= 5.3 Hz), 113.56 (d, J = 25.6 Hz), 31.95, 30.77, 29.18 – 28.04 (m), 26.19,21.67, 13.10. HRMS-ESI m / z : [M+H]+ calcd for C33H27F6O2S+ 601.1630, found 601.1627 , Formula 7.

[0030] Example 8 Preparation of 4,5-bis(4-fluorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(fluorobenzene) (0.0242 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-fluorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 8, with a yield of 99%.

[0031] 1 H NMR (400 MHz, CDCl3) δ 7.03 (ddd, J = 8.9, 5.3, 1.4 Hz, 4H), 6.91 (td, J = 8.6, 5.9 Hz, 4H), 3.60 (s, 2H), 3.12 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.46 (s, 6F), -117.07 (td, J = 9.0, 5.0Hz, 1F), -117.17 – -117.40 (m, 1F). 13C NMR (152 MHz, CDCl3) δ 136.84, 136.24 (d, J = 3.4 Hz), 135.91 (d, J = 3.4 Hz), 133.06, 130.69 (d, J = 8.1 Hz), 130.32 (d, J = 8.0 Hz), 127.54 -121.90 (m), 115.41 (dd, J = 21.5, 19.9 Hz), 62.96 – 56.91 (m), 32.87, 31.61. HRMS-ESI m / z: [M+Na]+ calcd for C19H12F8NaS+ 447.0424, found447.0432. , Formula 8.

[0032] Example 9 Preparation of 4,5-bis(4-chlorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(chlorobenzene) (0.0274 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(4-chlorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 9, with a yield of 99%.

[0033] 1 H NMR (600 MHz, CDCl3) δ 7.14 – 7.06 (m, 4H), 6.91 – 6.84 (m, 4H), 3.49 (s, 2H), 3.00 (s, 2H). 19 F NMR (565 MHz, CDCl3) δ -73.43(s, 6F). 13C NMR (152 MHz, CDCl3) δ 137.47, 137.14, 136.16, 132.66 – 132.18(m), 129.40, 129.24, 129.03, 128.88, 128.02, 127.74, 127.62, 127.39, 124.56,122.67,58.92-59.09 (m), 33.56, 31.71, 30.51, 28.49 (d, J = 57.0 Hz). HRMS-ESI m / z : [M+H]+ calcd for C19H13Cl2F6S+ 457.0014, found456.5372. , Formula 9.

[0034] Example 10 Preparation of 4,5-bis(4-bromophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(bromobenzene) (0.0361 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to prepare 4,5-bis(4-bromophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 10, with a yield of 99%.

[0035] 1 H NMR (400 MHz, CDCl3) δ 7.39 – 7.32 (m, 4H), 7.02 – 6.80 (m, 4H), 3.58 (s, 2H), 3.09 (s, 2H). 19 F NMR (565 MHz, CDCl3) δ -73.55(s,6F). 13C NMR (152 MHz, CDCl3) δ 136.03, 135.42 (d, J = 3.4 Hz), 135.10 (d,J = 3.4 Hz), 132.25, 129.88 (d, J = 8.1 Hz), 129.51 (d, J = 8.0 Hz), 126.73 -121.09(m), 114.74, 114.60 (d, J = 1.6 Hz), 114.46, 59.81 – 58.88 (m), 32.05,30.80. HRMS-ESI m / z: [M+Na]+ calcd for C19H12Br2F6NaS+ 566.8823, found566.8838. , Formula 10.

[0036] Example 11 Preparation of dimethyl 4,4'-(6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran-3,4-diyl)dibenzoate Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)dimethyl benzoate (0.0322 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain dimethyl 4,4'-(6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran-3,4-diyl)dibenzoate as shown in Formula 11, with a yield of 99%.

[0037] 1 H NMR (400 MHz, CDCl3) δ 7.92 – 7.82 (m, 4H), 7.18 – 7.05 (m, 4H), 3.90 (d, J = 2.2 Hz, 6H), 3.64 (s, 2H), 3.15 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -73.53(s,6F). 13 C NMR (152 MHz, CDCl3) δ 166.50 (d, J = 3.8 Hz), 144.60, 144.27,138.37, 134.41, 129.76, 129.63, 129.24, 129.14, 129.01, 128.62-123.69 (m) ,60.45-59.74 (m), 52.15 (d, J = 3.7 Hz), 32.55, 31.37. HRMS-ESI m / z : [M+H]+ calcd for C23H19F6O4S+ 505.0903, found505.0906. , Formula 11.

[0038] Example 12 Preparation of 3,4-bis(4-cyanophenyl)-6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)dibenzonitrile (0.0256 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,4-bis(4-cyanophenyl)-6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran as shown in Formula 12, with a yield of 99%.

[0039] 1 H NMR (400 MHz, CDCl3) δ 7.63 – 7.46 (m, 4H), 7.21 – 7.10 (m, 4H), 3.63 (s, 2H), 3.14 (s, 2H). 19F NMR (565 MHz, CDCl3) δ -73.52(s,6F). 13 C NMR (152 MHz, CDCl3) δ 144.14, 143.83, 138.69, 134.65, 132.49,132.37, 129.90, 129.80, 129.66, 129.28, 125.44-123.56(m), 118.17, 111.81 (d,J = 11.6 Hz), 60.40-60.13 (m), 32.54, 31.30. HRMS-ESI m / z : [M+Na]+ calcd for C21H12F6N2NaS+ 461.0518, found461.0521. , Equation 12.

[0040] Example 13 Preparation of 2,2-bis(trifluoromethyl)-4,5-bis(4-trifluoromethylphenyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 4,4'-(1,3-butadiene-2,3-diyl)bis(ethoxyphenyl) (0.0342 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 2,2-bis(trifluoromethyl)-4,5-bis(4-trifluoromethylphenyl)-3,6-dihydro-2H-thiapyran as shown in Formula 13, with a yield of 79%.

[0041] 1 H NMR (400 MHz, CDCl3) δ 7.47 (dd, J = 8.0, 4.4 Hz, 2H), 7.35 (t, J= 7.7 Hz, 2H), 7.30 – 7.20 (m, 4H), 3.67 (s, 2H), 3.17 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -66.19 (s,3F), -66.27 (s 3F), -73.51 (s,6F). 13 C NMR (152 MHz, CDCl3) δ 140.48, 140.13, 137.90, 134.05, 132.03,131.81, 130.96 (qd, J = 32.5, 23.6 Hz), 129.05 (d, J = 10.9 Hz), 126.34,126.09, 125.91 (q, J = 3.8 Hz), 125.56, 125.38 (q, J = 3.8 Hz), 124.54,124.36 (dq, J = 12.3, 3.7 Hz), 126.34-120.93(m), 60.30-59.66 (m), 32.50, 31.25. HRMS-ESI m / z : [M+H]+ calcd for C21H13F12S+ 525.0541, found 525.0539. , Formula 13.

[0042] Example 14 Preparation of 4,5-bis(m-tolyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis(methylbenzene) (0.0234 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(m-tolyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 14, with a yield of 99%.

[0043] 1H NMR (600 MHz, CDCl3) δ 6.95 (q, J = 7.8 Hz, 2H), 6.88 (tdt, J =7.6, 2.1, 1.0 Hz, 2H), 6.83 – 6.78 (m, 2H), 6.74 – 6.68 (m, 2H), 3.50 (s,2H), 3.02 (s, 2H), 2.14 (d, J = 7.5 Hz, 6H). 19 F NMR (565 MHz, CDCl3) δ -73.48(s, 6F). 13 C NMR (152 MHz, CDCl3) δ 140.50, 140.23, 137.85, 137.62, 137.25,133.48, 129.45, 129.04, 128.03, 127.88 (d, J = 1.6 Hz), 127.81, 126.27,125.89, 125.75-123.87(m), 60.75 – 59.48 (m), 32.77, 31.69, 21.36 (d, J = 7.0Hz). HRMS-ESI m / z : [M+H]+ calcd for C21H19F6S+ 417.1106, found 417.1122. , Equation 14.

[0044] Example 15 Preparation of 4,5-bis(3-methoxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis(methoxybenzene) (0.0266 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(3-methoxyphenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 15, with a yield of 99%.

[0045] 1 H NMR (400 MHz, CDCl3) δ 7.14 (td, J = 8.0, 6.6 Hz, 2H), 6.74 (dddd,J = 8.3, 3.4, 2.5, 0.9 Hz, 2H), 6.69 (dq, J = 6.8, 1.2 Hz, 2H), 6.60 (td, J =2.8, 1.6 Hz, 2H), 3.65 (s, 3H), 3.63 (s, 3H), 3.62 (s, 2H), 3.14 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.50 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 159.29 (d, J = 21.3 Hz), 141.67 (d, J =42.0 Hz), 137.43, 133.70, 129.27 (d, J = 24.4 Hz), 127.59-121.11 (m), 114.30 (d, J = 41.4 Hz), 113.09 (d, J = 13.6 Hz), 60.39-59.87 (m), 55.10 (d, J =11.5 Hz), 32.70, 31.52. HRMS-ESI m / z : [M+H]+ calcd for C21H19F6O2S+ 449.1004, found449.0997. , Formula 15.

[0046] Example 16 Preparation of 4,5-bis(3-fluorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis(fluorobenzene) (0.0242 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(3-fluorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 16, with a yield of 99%.

[0047] 1 H NMR (400 MHz, CDCl3) δ 7.02 (ddd, J = 9.0, 5.3, 1.9 Hz, 4H), 6.91 (td, J = 8.7, 5.9 Hz, 4H), 3.60 (s, 2H), 3.12 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.49(6F), -117.08 (m,1F), -117.24 – -117.35 (m,1F). 13C NMR (152 MHz, CDCl3) δ 163.37 (d, J = 12.0 Hz), 161.74 (d, J =11.7 Hz), 142.17 (d, J = 7.7 Hz), 141.82 (d, J = 7.6 Hz), 137.42, 133.59 (d,J = 2.3 Hz), 130.05 (d, J = 8.4 Hz), 129.89 (d, J = 8.5 Hz), 124.70 (d, J =2.9 Hz), 127.47-121.84 (m), 123.71, 115.92, 115.77, 115.54, 115.39, 114.55(dd, J = 21.0, 9.7 Hz), 60.35-59.65(m), 32.67, 31.43. HRMS-ESI m / z : [M+H]+ calcd for C19H13F8S+ 425.0605, found 425.0607. , Formula 16.

[0048] Example 17 Preparation of 4,5-bis(3-chlorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis(chlorobenzene) (0.0274 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(3-chlorophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 17, with a yield of 99%.

[0049] 1H NMR (600 MHz, CDCl3) δ 7.09 (dddd, J = 7.9, 5.7, 2.1, 1.1 Hz, 2H), 7.03 (td, J = 7.8, 5.9 Hz, 2H), 6.99 (t, J = 1.9 Hz, 1H), 6.96 (t, J = 1.9Hz, 1H), 6.79 (dtd, J = 7.7, 1.8, 1.1 Hz, 2H), 3.49 (s, 2H), 3.00 (s, 2H). 19 F NMR (565 MHz, CDCl3) δ -73.52 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 141.74, 141.38, 137.41, 134.38, 134.24,133.55, 129.70, 129.58, 128.79, 128.36, 127.74 (d, J = 10.4 Hz), 127.32,126.96, 126.90-121.76(m), 63.92 – 57.03(m), 32.60, 31.40. HRMS-ESI m / z : [M+Na]+ calcd for C19H11Cl2F6NaS+ 478.9833, found478.9825. , Formula 17.

[0050] Example 18 Preparation of 4,5-bis(3-bromophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis(bromobenzene) (0.0361 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(3-bromophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 18, with a yield of 99%.

[0051] 1 H NMR (400 MHz, CDCl3) δ 7.38 – 7.32 (m, 2H), 7.24 (dt, J = 12.3,1.9 Hz, 2H), 7.07 (td, J = 7.9, 3.2 Hz, 2H), 6.93 (d, J = 8.1 Hz, 2H), 3.59(s, 2H), 3.10(s, 2H). 19 F NMR (565 MHz, CDCl3) δ -73.53 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 163.42 (d, J = 7.9 Hz), 161.78 (d, J = 8.1Hz), 137.60, 137.00 (d, J = 3.4 Hz), 136.67 (d, J = 3.4 Hz), 133.83, 131.46(d, J = 8.1 Hz), 131.08 (d, J = 8.0 Hz), 128.89 – 122.14 (m), 116.18 (dd, J =21.5, 19.9 Hz), 64.98 – 57.53 (m), 33.63, 32.38. HRMS-ESI m / z : [M+Na]+ calcd for C19H12Br2F6NaS+ 566.8823, found566.8813 , Formula 18.

[0052] Example 19 Preparation of 3,4-bis(3-cyanophenyl)-6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)dibenzonitrile (0.0256 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,4-bis(3-cyanophenyl)-6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran as shown in Formula 19, with a yield of 99%.

[0053] 1 H NMR (400 MHz, CDCl3) δ 7.53 (ddt, J = 7.7, 3.6, 1.4 Hz, 2H), 7.37 (td, J = 7.8, 3.4 Hz, 2H), 7.33 (t, J = 1.7 Hz, 1H), 7.31 (t, J = 1.7 Hz,1H), 7.27 (ddq, J = 8.0, 3.1, 1.5 Hz, 2H), 3.62 (s, 2H), 3.13 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.52 (s, 6F). 13C NMR (152 MHz, CDCl3) δ 140.82, 140.44, 137.91, 133.92, 133.29,132.95, 132.33, 131.88, 131.46 (d, J = 11.5 Hz), 129.62 (d, J = 12.4 Hz), 128.71 – 121.06 (m), 118.05 (d, J = 8.9 Hz), 113.03 (d, J = 16.2 Hz), 60.41-59.70 (m), 32.58, 31.30. HRMS-ESI m / z : [M+H]+ calcd for C21H13F6N2S+ 439.0698, found439.0714. , Formula 19.

[0054] Example 20 Preparation of 4,5-bis(3-nitrophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis(nitrobenzene) (0.0296 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(3-nitrophenyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 20, with a yield of 97%.

[0055] 1H NMR (600 MHz, CDCl3) δ 8.00 (dddd, J = 8.3, 5.1, 2.3, 1.1 Hz, 2H), 7.87 (t, J = 2.0 Hz, 1H), 7.85 (t, J = 2.0 Hz, 1H), 7.32 (td, J = 8.0, 2.3Hz, 2H), 7.26 (ddt, J = 7.6, 1.6, 0.8 Hz, 2H), 3.59 (s, 2H), 3.10 (s, 2H). 19 F NMR (565 MHz, CDCl3) δ -73.50 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 148.32 (d, J = 12.5 Hz), 141.07, 140.66,140.02, 139.43, 138.15, 135.29, 134.92, 134.67, 134.15, 129.73, 129.56,125.45 (d, J = 2.2 Hz), 123.80, 123.57, 123.29, 123.03, 122.93, 123.93-122.84(m), 63.17 – 57.05 (m), 32.61, 31.34. HRMS-ESI m / z : [M+H]+ calcd for C19H13F6N2O4S+ 479.0495, found479.0495. , Formula 20.

[0056] Example 21 Preparation of 2,2-bis(trifluoromethyl)-4,5-bis(3-trifluoromethylphenyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,3'-(1,3-butadiene-2,3-diyl)bis((trifluoromethyl)benzene) (0.0342 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 2,2-bis(trifluoromethyl)-4,5-bis(3-trifluoromethylphenyl)-3,6-dihydro-2H-thiapyran as shown in Formula 21, with a yield of 76%.

[0057] 1 H NMR (400 MHz, CDCl3) δ 7.52 – 7.44 (m, 2H), 7.36 (t, J = 7.8 Hz,2H), 7.28 – 7.22 (m, 4H), 3.67 (s, 2H), 3.18 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -66.18 (d, J = 28.5 Hz, 6F), -73.46 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 140.49, 140.13, 137.90, 134.05, 132.03,131.81, 130.96 (qd, J = 32.5, 23.8 Hz), 129.04 (d, J = 10.9 Hz), 126.35,125.91 (q, J = 3.8 Hz), 125.56, 125.38 (q, J = 3.8 Hz), 124.54, 124.36 (dq, J= 12.2, 3.8 Hz), 126.33-120.93(m), 60.37-59.66 (m), 32.49, 31.24. HRMS-ESI m / z : [M+H]+ calcd for C21H13F12S+ 525.0541, found 525.0544. , Equation 21.

[0058] Example 22 Preparation of 4,5-bis(2-naphthyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 2,2'-(1,3-butadiene-2,3-diyl)naphthalene (0.0306 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(2-naphthyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 22, with a yield of 79%.

[0059] 1 H NMR (400 MHz, CDCl3) δ 8.11 – 7.86 (m, 1H), 7.81 – 7.66 (m, 5H), 7.57 (dd, J = 16.7, 8.5 Hz, 2H), 7.46 (qt, J = 4.6, 2.5 Hz, 4H), 7.12 (ddd, J= 8.9, 7.4, 1.8 Hz, 2H), 3.79 (s, 2H), 3.32 (s, 2H). 19 F NMR (376 MHz, CDCl3) δ -73.50 (s, 6F). 13C NMR (126 MHz, CDCl3) δ 137.69, 133.98, 133.24 (d, J = 5.1 Hz), 132.37 (d, J = 8.5 Hz), 128.09 – 127.37 (m), 127.06, 126.20 (d, J = 11.1 Hz),124.62, 123.69 (d, J = 13.2 Hz), 118.76, 60.89-60.04 (m), 33.28, 32.15,25.68. HRMS-ESI m / z : [M+H]+ calcd for C27H19F6S+ 489.1106, found 489.1105. , Equation 22.

[0060] Example 23 Preparation of 2,2-bis(trifluoromethyl)-4,5-bis(3,4,5-trimethoxyphenyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 5,5'-(1,3-butadiene-2,3-diyl)bis(1,2,3-trimethoxybenzene) (0.0386 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 2,2-bis(trifluoromethyl)-4,5-bis(3,4,5-trimethoxyphenyl)-3,6-dihydro-2H-thiapyran as shown in Formula 23, with a yield of 42%.

[0061] 1 H NMR (400 MHz, CDCl3) δ 6.29 (d, J = 7.2 Hz, 4H), 3.82 (d, J = 2.2Hz, 6H), 3.67 (d, J = 6.1 Hz, 12H), 3.62 (s, 2H), 3.13 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -73.48 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 152.99 (d, J = 30.5 Hz), 138.14 – 136.56(m), 135.59, 133.59, 125.70, 106.12 (d, J = 48.4 Hz), 60.91-59.66 (m), 56.09(d, J = 21.6 Hz), 32.60, 31.34. HRMS-ESI m / z : [M+H]+ calcd for C25H27F6O6S+ 569.1427, found , Equation 23.

[0062] Example 24 Preparation of 4,5-bis(2-thienyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 2,2'-(butyryneth-1,3-diyl)dithiophene (0.0218 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 4,5-bis(2-thienyl)-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 24, with a yield of 48%.

[0063] 1 H NMR (600 MHz, CDCl3) δ 7.21 – 7.19 (m, 2H), 6.89 – 6.86 (m, 3H), 6.85 (dd, J = 3.6, 1.2 Hz, 1H), 3.53 (s, 2H), 3.07 (s, 2H). 19F NMR (565 MHz, CDCl3) δ -73.61 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 140.67, 140.40, 137.63, 133.90, 129.21,128.85, 128.48, 128.34, 127.36 (d, J = 11.5 Hz), 126.25 – 123.49 (m), 60.44-60.09(m), 33.02 (t, J = 1.9 Hz), 31.84. HRMS-ESI m / z : [M+Na]+ calcd for C15H10F6NaS3+ 422.9741, found422.2076. , Equation 24.

[0064] Example 25 Preparation of diethyl 2,2'-(6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran-3,4-diyl)diacetate Under anhydrous and oxygen-free conditions, diethyl 3,4-dimethylene adipate (0.0226 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain diethyl 2,2'-(6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran-3,4-diyl)diacetate as shown in Formula 25, with a yield of 98%.

[0065] 1 H NMR (600 MHz, CDCl3) δ 4.07 (qd, J = 7.1, 3.4 Hz, 4H), 3.20 (d, J= 2.6 Hz, 4H), 3.17 (s, 2H), 2.67 (s, 2H), 1.22 – 1.13 (m, 6H). 19F NMR (565 MHz, CDCl3) δ -73.86 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 170.13, 169.67, 131.51, 127.82, 127.54 –121.41 (m), 61.17, 59.96-59.25 (m), 39.07, 38.53, 30.91, 29.58, 14.04 (d, J =3.0 Hz). HRMS-ESI m / z : [M+H]+ calcd for C15H19F6O4S+ 409.0903, found 409.0913 , Formula 25.

[0066] Example 26 Preparation of 3,4-bis(2-acetoxyethyl)-6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, 3,4-dimethylhexane-1,6-dimethyldiacetic acid ester (0.0226 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,4-bis(2-acetoxyethyl)-6,6-bis(trifluoromethyl)-5,6-dihydro-2H-thiapyran as shown in Formula 26, with a yield of 99%.

[0067] 1 H NMR (400 MHz, CDCl3) δ 4.13 (td, J = 6.8, 5.1 Hz, 4H), 3.14 (s,2H), 2.61 (s, 2H), 2.59 – 2.51 (m, 4H), 2.04 (d, J = 2.8 Hz, 6H). 19F NMR (376 MHz, CDCl3) δ -73.78 (s, 6F). 13 C NMR (152 MHz, CDCl3) δ 170.85 (d, J = 8.6 Hz), 133.88, 129.99,128.00 – 120.86 (m), 77.75 – 76.24 (m), 62.56, 62.11, 60.04 (p, J = 26.4 Hz),32.63, 31.90, 30.42, 29.20, 20.78 (d, J = 4.4 Hz). HRMS-ESI m / z : [M+H]+ calcd for C15H19F6O4S+ 409.0903, found409.0905. , Equation 26.

[0068] Example 27 Preparation of (1R,4S)-3,3-bis(trifluoromethyl)-2-thiabicyclo[2.2.2]oct-5-ene Under anhydrous and oxygen-free conditions, cyclohexyl-1,3-diene (0.008 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain (1R,4S)-3,3-bis(trifluoromethyl)-2-thiabicyclo[2.2.2]oct-5-ene as shown in Figure 27, with a yield of 75%.

[0069] 1H NMR (400 MHz, CDCl3) δ 6.61 (t, J = 7.6 Hz, 1H), 6.41 (dddd, J =8.3, 7.0, 2.9, 1.2 Hz, 1H), 3.68 (t, J = 5.4 Hz, 1H), 3.43 (dddd, J = 7.4,4.3, 1.7 Hz, 1H), 2.25 – 2.05 (m, 2H), 1.91 – 1.70 (m, 1H). 19 F NMR (376 MHz, CDCl3) δ -68.06 (q, J = 11.8 Hz, 3F), -71.80 (qd, J =11.8, 3.2 Hz, 3F). 13 C NMR (152 MHz, CDCl3) δ 133.53, 133.41 (d, J = 2.4 Hz), 127.32-121.66 (m), 62.87 – 61.94 (m), 35.24, 31.66, 25.64, 21.57 – 20.87 (m). HRMS-ESI m / z : [M+H]+ calcd for C9H9F6S+ 263.0324, found , Equation 27.

[0070] Example 28 Preparation of 3,6-dipropyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, (4E,6E)-decacarbon-4,6-diene (0.0138 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,6-dipropyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 28, with a yield of 99%.

[0071] 1 H NMR (400 MHz, CDCl3) δ 6.19 – 6.06 (m, 1H), 5.77 (ddt, J = 9.3,6.5, 3.1 Hz, 1H), 3.94 – 3.23 (m, 1H), 2.52 – 2.24 (m, 1H), 2.06 (ddt, J =45.8, 19.0, 8.1 Hz, 1H), 1.82 – 1.24 (m, 7H), 1.14 – 0.90 (m, 6H). 19 F NMR (376 MHz, CDCl3) δ -66.81 (dq, J = 17.9, 9.5 Hz,3F), -69.50 –-69.74 (m,3F). 13 C NMR (152 MHz, CDCl3) δ 134.57, 133.95, 132.74, 132.59, 132.16,128.48 – 120.47 (m), 64.87 – 63.75 (m), 40.64, 40.15, 39.11, 38.85, 38.37,38.16, 35.20, 32.81 (dd, J = 5.1, 2.9 Hz), 31.17, 30.38, 29.17, 26.22, 23.84(t, J = 2.4 Hz), 22.43 (d, J = 6.0 Hz), 22.09, 20.29, 13.77 (d, J = 2.5 Hz). HMS-ESI m / z : [M+H]+ calcd for C13H19F6S+ 321.1106, found 321.1109. , Equation 28.

[0072] Example 29 Preparation of 3,6-dibutyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, (5E,7E)-dodecane-5,7-diene (0.0166 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,6-dibutyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 29, with a yield of 80%.

[0073] 1 H NMR (400 MHz, CDCl3) δ 6.11 (ddd, J = 9.6, 4.1, 2.3 Hz, 1H), 5.77(dt, J = 10.0, 3.4 Hz, 1H), 3.56 – 3.49 (m, 1H), 2.50 – 2.31 (m, 1H), 2.05(q, J = 9.3 Hz, 1H), 1.80 – 1.23 (m, 11H), 1.03 – 0.85 (m, 6H). 19 F NMR (376 MHz, CDCl3) δ -66.72 (q, J = 9.3 Hz, 3F), -69.59 (q, J =9.5 Hz, 3F). 13 C NMR (152 MHz, CDCl3) δ 134.47, 132.67, 128.07 - 121.45 (m), 64.79– 63.92 (m), 39.13 (d, J = 4.8 Hz), 38.85, 38.43 (d, J = 7.5 Hz), 38.16,35.19, 33.11, 32.81, 31.51 (d, J = 2.7 Hz), 31.20, 30.55 – 30.03 (m), 29.18,26.73, 23.22 – 22.02 (m), 14.06 – 13.53 (m). HRMS-ESI m / z: [M+Na]+ calcd for C15H22F6NaS+ 371.1239, found371.1252. , Equation 29.

[0074] Example 30 Preparation of 3,6-dipentyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, (6E,8E)-tetradec-6,8-diene (0.0194 g, 0.1 mmol), HFA·3H₂O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh₃ (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl₂ (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,6-dipentyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 30, with a yield of 99%.

[0075] 1 H NMR (400 MHz, CDCl3) δ 6.11 (ddd, J = 9.7, 3.8, 2.6 Hz, 1H), 5.77 (dt, J = 9.6, 3.3 Hz, 1H), 3.53 (dt, J = 9.1, 5.1 Hz, 1H), 2.50 – 2.31 (m,1H), 2.04 (td, J = 12.1, 4.6 Hz, 1H), 1.83 – 1.21 (m, 15H), 1.08 – 0.82 (m,6H). 19 F NMR (376 MHz, CDCl3) δ -66.72 (q, J = 9.3 Hz, 3F), -69.59 (q, J =9.4 Hz, 3F). 13C NMR (152 MHz, CDCl3) δ 134.47, 132.67, 128.07 - 121.45 (m), 64.34- 64.02 (m), 33.11 (d, J = 5.1 Hz), 32.82, 31.68, 31.61 – 31.38 (m), 31.20,30.70 – 30.46 (m), 30.38, 29.19, 29.03 (d, J = 3.5 Hz), 28.73, 27.02, 26.74,22.92 – 21.98 (m), 14.36 – 13.16 (m). HRMS-ESI m / z : [M+H]+ calcd for C17H27F6S+ 377.1732, found 377.1739. , Formula 30.

[0076] Example 31 Preparation of 3,6-dihexyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran Under anhydrous and oxygen-free conditions, (7E,9E)-hexadec-7,9-diene 3 (0.0222 g, 0.1 mmol), HFA·3H2O (19.6 μL, 1.4 mmol), MgO (12 mg, 3.0 mmol), and PPh3 (94 mg, 3.6 mmol) were added sequentially to a sealed tube that had been dried in an oven. Then, 1 mL of anhydrous 1,1,2-trichloroethane was added. SOCl2 (14.6 μL, 2.0 mmol) was rapidly injected into the reaction system using a microsyringe, and the stopcock was immediately tightened. The reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the reaction solution was concentrated by rotary evaporation under reduced pressure. The concentrate was then separated by column chromatography using ethyl acetate:petroleum ether as the eluent. The column chromatography effluent was concentrated by rotary evaporation and dried to obtain 3,6-dihexyl-2,2-bis(trifluoromethyl)-3,6-dihydro-2H-thiapyran as shown in Formula 31, with a yield of 99%.

[0077] 1H NMR (400 MHz, CDCl3) δ 6.00 (dt, J = 9.7, 3.2 Hz, 1H), 5.66 (dt, J= 9.7, 3.3 Hz, 1H), 3.42 (p, J = 5.1 Hz, 1H), 2.29 (d, J = 11.5 Hz, 1H), 1.93(td, J = 12.4, 4.5 Hz, 1H), 1.69 – 1.48 (m, 3H), 1.42 – 1.32 (m, 3H), 1.29 –1.12 (m, 13H), 0.82 (tt, J = 7.0, 3.2 Hz, 6H). 19 F NMR (376 MHz, CDCl3) δ -66.75 (q, J = 9.4 Hz, 3F), -69.62 (q, J =9.4 Hz, 3F). 13 C NMR (152 MHz, CDCl3) δ 134.47 (d, J = 2.8 Hz), 132.66, 128.07,127.12, 126.19 - 121.45(m), 64.66 - 64.01 (m), 39.15, 38.46, 29.33 (d, J =5.5 Hz), 29.16 (d, J = 5.4 Hz), 29.03 (d, J = 4.2 Hz), 28.73, 27.06, 27.01,26.74, 22.69 – 22.35 (m), 14.93 – 12.50 (m). HRMS-ESI m / z : [M+H]+ calcd for C19H31F6S+ 405.2045, found 405.2060. , Equation 31.

[0078] In addition, this invention conducted antitumor activity tests on various cancer cell lines using gem-bis(trifluoromethyl)dihydrothiapyran: Specific experimental procedures: Human cervical cancer cells (HeLa), mouse breast cancer cells (4T1), and human liver cancer cells (HepG2) were cultured in DMEM complete medium. When they reached the logarithmic growth phase, the cells were digested with trypsin, and the cell suspension was diluted to approximately 8 × 10⁸ cells / mL. 4Cells were seeded. 100 μL of cell suspension was then seeded into each well of a 96-well plate and cultured at 37°C and 5% CO2 for 24 h. After cell adhesion, drug treatment was performed. Compound solutions of different concentration gradients (from 100 to 0.78125 μM, decreasing in a gradient) were prepared using DMEM complete medium, with three replicates for each concentration and two blank control groups. The 96-well plates were then incubated for 48 h. After 48 h of culture, the culture medium was removed, the cells were washed with PBS buffer, and 10% CCK-8 solution (prepared using phenol red-free DMEM complete medium) was added under light-protected conditions and incubated for 1 to 2 h. Finally, the absorbance (OD value) of each well was measured at 450 nm using a microplate reader. The half-inhibitory concentration (IC50) of the cells could be calculated based on the obtained OD values. 50 Data were obtained for the antitumor activity of several compounds using 5-FU as a positive control. The results are shown in Table 1.

[0079] Table 1 Antitumor activity data of embodiments of the present invention

[0080] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A rapid synthesis method for geminobis(trifluoromethyl)dihydrothiapyran compounds, characterized in that: The process includes the following steps: Under anhydrous and oxygen-free conditions, a sulfur source, a reducing agent, and a hexafluoroisopropylating agent are dissolved in an anhydrous solvent. The system is activated at room temperature to generate a hexafluoroisopropyl polysulfide intermediate. Then, an activator and a substrate conjugated diene are added and stirred at high speed. The hexafluoroisopropyl polysulfide is dehydrated by the activator to obtain the intermediate, which undergoes a Diels-Alder reaction with the conjugated diene to give the product gem-bis(trifluoromethyl)dihydrothiapyran compound.

2. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The hexafluoroisopropylating agent is hexafluoroacetone trihydrate.

3. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The sulfur source is thionyl chloride.

4. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The reducing agent is triphenylphosphine.

5. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The anhydrous solvents include: 1,1,2-trichloroethane, 1,1,2,2-tetrachloroethane, carbon tetrachloride, dimethyl sulfoxide, N,N-dimethylformamide, 1,4-dioxane, and toluene.

6. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The catalysts include: magnesium oxide, calcium oxide, aluminum oxide, silicon dioxide, phosphorus pentoxide, magnesium sulfate, and magnesium chloride.

7. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The conjugated dienes include terminal olefins and non-terminal olefins.

8. The method for preparing gem-bis(trifluoromethyl)dihydrothiapyran compounds according to claim 1, characterized in that: The preferred conditions for the stirring reaction are stirring at 110°C for 12 hours.

9. A geminobis(trifluoromethyl)dihydrothiapyran compound as described in any one of claims 1-8, characterized in that: Its structure is shown in Equation I: ， Formula I In Formula I, R1 and R2 are the same group, which are aryl, naphthyl, or thiophene.

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