A reaction method for the selective fluorination functionalization of gem-difluoroolefins

Abstract

The present invention relates to the field of chemical synthesis technology, and specifically discloses a reaction method for the selective fluorination functionalization of gem-difluoroolefins. This method uses gem-difluoroolefins, hydrogen fluoride triethylamine, and nucleophiles as raw materials, adds an organic solvent for an electrochemical reaction, and obtains products with fluorination at the 1-position or 2-position of the gem-difluoroolefins. This method is a novel electrochemical reaction new strategy for the selective fluorination functionalization of gem-difluoroolefins, provides a new synthesis process for polyfluorinated compounds with simple process, mild conditions, and low cost, and all the obtained compounds have new structures.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and particularly relates to a reaction method for the selective fluorination functionalization of gem-difluoroolefins. Background Art

[0002] Fluorine atoms are often introduced into the design of drug molecules due to their unique physical and chemical properties. It is reported that about 20% of drugs and 30% of pesticide molecules contain carbon-fluorine bonds, and fluorinated organic molecules cannot be synthesized naturally. Therefore, the research on the synthesis of organic fluorides using inexpensive and readily available fluorine-containing building blocks has attracted increasing attention. At the same time, fluorine-containing molecules with different structures have their own advantages in the fields of drugs, pesticides, and materials. Therefore, it is very necessary to develop a method for accurately introducing fluorine atoms under mild conditions to obtain fluorine-containing substances with rich structures. Although great progress has been made in selective fluorination research, the selective synthesis of polyfluorinated organic compounds is still extremely challenging. Gem-difluoroolefins can be prepared from carbonyl compounds through classical reactions such as Wittig, Horner-Wadsworth-Emmons, etc. The strong electron-withdrawing effect of the two fluorine atoms on the olefin makes it exhibit unique reactivity. Many chemists at home and abroad have reported on its transformation reactions, but generally involve the use of noble metal catalysts, the addition of stoichiometric chemical oxidants, and inert and harsh reaction conditions, which are difficult to promote in actual production. Therefore, it is very important to develop an efficient and mild reaction for the selective fluorination functionalization of gem-difluoroolefins to synthesize polyfluorinated molecules with rich structures. Summary of the Invention

[0003] In order to overcome at least one of the technical problems existing in the prior art, the present invention provides a reaction method for the selective fluorination functionalization of gem-difluoroolefins.

[0004] This method provides a novel electrochemical reaction strategy for the selective fluorination functionalization of gem-difluoroolefins, and provides a new process for the synthesis of polyfluorinated compounds with simple process, mild conditions, and low cost. The obtained compounds are all new structures.

[0005] The technical solution of the present invention is as follows:

[0006] A reaction method for the selective fluorination functionalization of gem-difluoroolefins, which uses gem-difluoroolefins, hydrogen fluoride triethylamine, and a nucleophile as raw materials, adds an organic solvent for an electrochemical reaction to obtain a fluorinated product at the 1-position or 2-position of the gem-difluoroolefin;

[0007] Among them, the gem-difluoroolefin has a structural formula as shown in Formula I; the fluorinated product at the 1-position of the gem-difluoroolefin is as shown in Formula V; the fluorinated product at the 2-position of the gem-difluoroolefin is as shown in Formula VI;

[0008]

[0009] R1 in Formula I, Formula V and Formula VI is selected from any one of the following groups: phenyl, (trifluoromethoxy)phenyl, (2,2-difluorovinyl)phenyl, 1,3-difluorophenyl, thienyl, benzoic acid group;

[0010] R2 in Formula VI is selected from any one of the following groups: fluorine, chlorine, bromine, iodine.

[0011] Preferably, the specific reaction method for the fluorination product at the 1-position of the gem-difluoroolefin is as follows:

[0012] Step (1a): Dissolve the gem-difluoroolefin in an organic solvent, then add tetrabutylammonium tetrafluoroborate, triethylamine hydrogen fluoride and methanol to obtain a reaction raw material mixture;

[0013] Step (2a): Stir the reaction raw material mixture in air at room temperature, and perform an electrolysis reaction with a carbon plate as the anode and a platinum plate electrode as the cathode; after the reaction is completed, separate and purify the product to obtain the fluorination product at the 1-position of the gem-difluoroolefin.

[0014] Preferably, the organic solvent described in step (1a) consists of dichloromethane and hexafluoroisopropanol.

[0015] Preferably, the volume ratio of the dichloromethane to the hexafluoroisopropanol is 2-4:1.

[0016] Most preferably, the volume ratio of the dichloromethane to the hexafluoroisopropanol is 3:1.

[0017] Preferably, the dosage ratio of tetrabutylammonium tetrafluoroborate to triethylamine hydrogen fluoride and methanol in step (1a) is 0.1-0.2 g:1-2 mL:1-2 mL; most preferably, the dosage ratio of tetrabutylammonium tetrafluoroborate to triethylamine hydrogen fluoride and methanol in step (1a) is 0.165 g:1 mL:1 mL.

[0018] Preferably, the molar ratio of the gem-difluoroolefin to tetrabutylammonium tetrafluoroborate in step (1a) is 1:1.

[0019] Preferably, the voltage of the electrolysis reaction in step (2a) is 3-4 V, and the time of the electrolysis reaction is 3-5 h.

[0020] Most preferably, the voltage of the electrolysis reaction in step (2a) is 3.5 V, and the time of the electrolysis reaction is 4 h.

[0021] Preferably, the anode in step (2a) is a carbon plate (2.0 cm × 1.0 cm × 2.0 mm), and the cathode is a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm).

[0022] Preferably, the specific reaction method for the fluorination product at the 2-position of the gem-difluoroolefin is as follows:

[0023] Step (1b): Dissolve the gem-difluoroolefin in an organic solvent, and then add tetrabutylammonium tetrafluoroborate, triethylamine hydrogen fluoride, and a pyrazole compound to obtain a reaction raw material mixture;

[0024] Step (2b): Stir the reaction raw material mixture in air at room temperature, and perform an electrolysis reaction with a carbon plate as the anode and a platinum plate electrode as the cathode; after the reaction is completed, separate and purify the product to obtain the gem-difluoroolefin 2-position fluorination product;

[0025] The pyrazole compound has a structural formula as shown in Formula IV;

[0026]

[0027] Among them, R2 in Formula IV is selected from any one of the following groups: fluorine, chlorine, bromine, iodine.

[0028] Preferably, the organic solvent in step (1b) is dichloromethane.

[0029] Preferably, the dosage ratio of tetrabutylammonium tetrafluoroborate to triethylamine hydrogen fluoride in step (1b) is 0.1 - 0.2 g: 1 - 2 mL.

[0030] Most preferably, the dosage ratio of tetrabutylammonium tetrafluoroborate to triethylamine hydrogen fluoride in step (1b) is 0.165 g: 1 mL.

[0031] Preferably, the molar ratio of the gem-difluoroolefin to tetrabutylammonium tetrafluoroborate in step (1b) is 1:1.

[0032] Most preferably, the molar ratio of the gem-difluoroolefin to the pyrazole compound in step (1b) is 1:4.

[0033] Preferably, the voltage of the electrolysis reaction in step (2b) is 3 - 4 V, and the time of the electrolysis reaction is 3 - 5 h.

[0034] Most preferably, the voltage of the electrolysis reaction in step (2b) is 3.5 V, and the time of the electrolysis reaction is 4 h.

[0035] Preferably, the anode in step (2b) is a carbon plate (2.0 cm × 1.0 cm × 2.0 mm), and the cathode is a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm).

[0036] The reaction mechanism of the present invention and the synthesis method designed in the present invention mainly rely on the oxidation of the substrate on the electrode surface to generate a cationic intermediate, and then different nucleophiles are selected. According to the different reactivity of the nucleophile and fluoride ion attacking the active cationic intermediate, the regulation is realized that the fluoride ion attacks first or the nucleophile attacks first. After the first attack occurs, the cationic intermediate generates a benzyl radical intermediate, and this radical intermediate is further oxidized on the electrode surface to generate a positive ion intermediate, and then is attacked by the nucleophile or fluoride ion to generate the final product. The driving force in the reaction process is only the current, and the selective fluorination reaction is realized by regulating the nucleophilic ability of the nucleophile.

[0037] Advantages:

[0038] (1) The electrochemical synthesis method is safe, green, mild in conditions and low in development cost:

[0039] The present invention adopts an electrochemical method with mild reaction conditions, that is, a constant cell voltage of 3.5 V, at room temperature, in an air atmosphere, without the need to use expensive metal catalysts, without the need to use special fluorination reagents, the electrode can be reused multiple times, using hydrofluoride as the fluorine source, the whole process is simple, and the reagents used are generally relatively cheap, having great industrial potential.

[0040] (2) The substrate has good compatibility, realizing the preparation of a variety of novel-structured polyfluorinated compounds:

[0041] In the method of the present invention, the gem-difluoro derivative can achieve 1-position or 2-position selective fluorination under mild reaction conditions, and the preparation of a variety of novel fluorine-containing compounds containing heteroatoms can be realized. The reaction has high functional group tolerance; the reaction can be started and terminated by controlling the switch of the external power supply, with flexible operation and easy control.

[0042] (3) The synthesized compounds have potential application value and great development prospects:

[0043] The method of the present invention can directly prepare polyfluorinated molecules. These fluorine-containing compounds with brand-new structures have not been reported at present. Based on the performance of fluorine-containing molecules in the fields of medicine and materials, there is a wide range of exploration space. Description of the Drawings

[0044] Figure 1 It is the electrochemical reaction flow chart of the 1-fluorination product of gem-difluoroolefin.

[0045] Figure 2 It is the electrochemical reaction flow chart of the 2-fluorination product of gem-difluoroolefin. Detailed Embodiments

[0046] The following further explains the present invention in conjunction with embodiments, but the embodiments do not limit the present invention in any form.

[0047] Example 1 Method for preparing 4-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl

[0048] First step: Add 4-(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction test tube, add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until 4-(2,2-difluoroethyl)-1,1'-biphenyl is completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol to the reaction test tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 4-(2,2-difluorovinyl)-1,1'-biphenyl has completely reacted. The experimental treatment is to drain the solution in the reaction; dissolve the solute in the reaction test tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass the petroleum ether through a silica gel column. Obtain the product white solid 4-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl. White solid (0.062 g, 0.25 mmol, 50% yield); R f = 0.35 petroleum ether). (See Structural formula 1b)

[0049]

[0050] Structure confirmation The structure is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C,): 7.63 (t, J = 8.37 Hz, 4H), 7.52 - 7.44 (m, 4H), 7.38 (t, J = 7.26 Hz, 1H), 4.59 - 4.53 (m, 1H), 3.47 (s, 3H). 13 13C NMR (75 MHz, CDCl3, 25 °C,): 142.7, 140.6, 131.5, 128.9 (d, J = 16.47 Hz, 1C), 127.8, 127.4 (d, J = 12.70, 1C), 122.1 (t, J = 280.16 Hz, 1C), 81.4 (dd, J = 61.76, 31.01 Hz, 1C), 58.4. 19FNMR (282 MHz, CDCl3, 25 °C): -76.6 (s, 3F). Mass spectrometry: GCMS (ESI-TOF) (m / z): calcd for C 15 H 13 F3O, 266.1, found, 266.1.

[0051] The synthesized compound was confirmed to be the target compound 4-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl by structural identification.

[0052] Example 2 Method for synthesizing 3,5-difluoro-4'-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl

[0053] First step: Add 3,5-difluoro-4'-vinyl-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction test tube, add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until 3,5-difluoro-4'-vinyl-1,1'-biphenyl is completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol to the reaction test tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 3,5-difluoro-4'-vinyl-1,1'-biphenyl has completely reacted. The experimental treatment is to drain the solution in the reaction; dissolve the solute in the reaction test tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin dry, and pass the petroleum ether through a silica gel column. The product obtained is colorless oil 3,5-difluoro-4'-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl. Colorless oil (0.058 g, 0.24 mmol, 48% yield); R f = 0.35 (petroleum ether). (See Structural formula 2b)

[0054]

[0055] Structure confirmation The structure is as follows: Nuclear magnetic resonance spectroscopy: 11H NMR (300 MHz, CDCl3, 25 °C): 7.57 - 7.54 (m, 2H), 7.51 (d, J = 9.99 Hz, 2H), 7.46 - 7.38 (m, 1H), 7.00 - 6.89 (m, 2H), 4.59 - 4.52 (m, 1H), 3.47 (s, 3H). 13 13C NMR (75 MHz, CDCl3, 25 °C): 163.0 (dd, J = 12.16, 202.04 Hz, 1C), 159.6 (d, J = 11.09, 203.89 Hz, 1C), 161.0 (d, J = 11.11 Hz, 1C), 136.4, 132.1, 131.7 - 131.5 (m, 1C), 129.3 (d, J = 2.94 Hz, 1C), 128.5, 124.7 (dd, J = 13.20, 3.62 Hz, 1C), 122.0 (t, J = 280.06 Hz, 1C), 111.9 (dd, J = 20.97, 3.83 Hz, 1C), 104.7 (dd, J = 25.25, 26.36 Hz, 1C), 82.4 (dd, J = 30.91, 61.82 Hz, 1C), 58.5. 19 19F NMR (282 MHz, CDCl3, 25 °C): -76.6 (s, 3F), -110.8 (d, J = 7.33 Hz, 1F), -113.42 (d, J = 7.87 Hz, 1F).

[0056] The compound synthesized through structure identification is indeed the target compound 3,5 - difluoro - 4'-(2,2,2 - trifluoro - 1 - methoxyethyl)-1,1'-biphenyl.

[0057] Method for preparing 4-(2,2 - difluorovinyl)-4'-(2,2,2 - trifluoro - 1 - methoxyethyl)-1,1'-biphenyl in Example 3

[0058] Step 1: Add 4-(2,2-difluorovinyl)-4'-vinyl-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until 4-(2,2-difluorovinyl)-4'-vinyl-1,1'-biphenyl is completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 4-(2,2-difluorovinyl)-4'-vinyl-1,1'-biphenyl has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry, and pass the solution through a silica gel column with petroleum ether. Obtain the product as a colorless oil, 4-(2,2-difluorovinyl)-4'-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl. Colorless oil (0.035 g, 0.15 mmol, 30% yield); R f = 0.32 (petroleum ether). (See Structural Formula 3b)

[0059]

[0060] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C): 7.65 (s, 1H), 7.62 (s, 1H), 7.60 (s, 1H), 7.57 (s, 1H), 7.51 (d, J = 8.13 Hz, 2H), 7.42 (d, J = 8.31 Hz, 2H), 5.38 - 5.28 (m, 1H), 5.59 - 4.52 (m, 1H), 3.47 (s, 3H). 1313C NMR (75 MHz, CDCl3, 25 °C): 160.5, 156.6 (d, J = 9.83 Hz, 1C), 152.7, 141.9, 139.1, 131.7, 130.0 (t, J = 6.36 Hz, 1C), 128.9, 128.3 - 128.2 (m, 1C), 127.5, 127.3, 122.1 (t, J = 280.14 Hz, 1C), 82.3 - 81.8 (m, 1C), 82.0 - 81.8 (m, 1C). 19 19F NMR (282 MHz, CDCl3, 25 °C): -76.6 (s, 3F), -110.8 (d, J = 7.33 Hz, 1F), -113.42 (d, J = 7.87 Hz, 1F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 17 H 13 F5KO + ([M + K] - ), 367.1, found, 367.1.

[0061] The synthesized compound was confirmed to be the target compound 4-(2,2-difluorovinyl)-4'-(2,2,2-trifluoro-1-methoxyethyl)-1,1'-biphenyl by structural identification.

[0062] Example 4 Method for preparing 4-(2,2,2-trifluoro-1-methoxyethyl)-4'-(trifluoromethyl)-1,1'-biphenyl

[0063] Step 1: Add 4-(trifluoromethyl)-4'-vinyl-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) into a dry 40 mL reaction tube. Add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until 4-(trifluoromethyl)-4'-vinyl-1,1'-biphenyl is completely dissolved. Then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol into the reaction tube. Stir the whole mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC. Stop the reaction when it is detected that 4-(trifluoromethyl)-4'-vinyl-1,1'-biphenyl has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it into a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) into the round-bottom flask and spin-dry it, and pass the petroleum ether through the silica gel column. Obtain the product as a colorless oil, 4-(2,2,2-trifluoro-1-methoxyethyl)-4'-(trifluoromethyl)-1,1'-biphenyl. Colorless oil (0.049 g, 0.18 mmol, 35% yield); R f = 0.35 (petroleum ether). (See Structural Formula 4b)

[0064]

[0065] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 H NMR (300 MHz, CDCl3, 25℃,): 7.71 (s, 4H), 7.65 (d, J = 8.31 Hz, 2H), 7.54 (d, J = 8.19 Hz, 2H), 4.60 - 4.54 (m, 1H), 3.47 (s, 3H). 13 C NMR (75 MHz, CDCl3, 25℃,): 144.1, 141.2, 132.6, 130.1, 129.7, 129.0, 127.6 (d, J = 1.53 Hz, 1C), 126.0 (dd, J = 7.40, 3.65 Hz, 1C), 122.6 (t, J = 239.98 Hz, 1C), 122.0, 81.3 (dd, J = 61.84, 30.77 Hz, 1C), 58.5. 1919F NMR (282 MHz, CDCl3, 25 °C): -62.5 (s, 3F), -76.6 (s, 3F). Mass spectrometry: HRMS (ESI-TOF) (m / z): calcd for C 16 H 12 F6NaO + ([M+Na] + ), 357.0685, found, 357.0691.

[0066] The synthesized compound was confirmed by structural identification to be the target compound 4-(2,2,2-trifluoro-1-methoxyethyl)-4'-(trifluoromethyl)-1,1'-biphenyl.

[0067] Example 5 Method for synthesizing 4-(2,2,2-trifluoro-1-methoxyethyl)-4'-(trifluoromethoxy)-1,1'-biphenyl

[0068] First step: Add 4-(trifluoromethoxy)-4'-vinyl-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until 4-(trifluoromethoxy)-4'-vinyl-1,1'-biphenyl is completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC. Stop the reaction when it is detected that 4-(trifluoromethoxy)-4'-vinyl-1,1'-biphenyl has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin dry, and pass through a silica gel column with petroleum ether. Obtain the product as a white solid, 4-(2,2,2-trifluoro-1-methoxyethyl)-4'-(trifluoromethoxy)-1,1'-biphenyl. White solid (0.027 g, 0.12 mmol, 23% yield); R f = 0.35 (petroleum ether). (See Structural Formula 5b)

[0069]

[0070] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy:1 1H NMR (300 MHz, CDCl3, 25 °C): 7.61 (d, J = 8.61 Hz, 4H), 7.52 (d, J = 8.04 Hz, 2H), 7.31 (d, J = 8.31 Hz, 2H), 4.60 - 4.53 (m, 1H), 3.47 (s, 3H). 13 13C NMR (75 MHz, CDCl3, 25 °C): 149.1, 141.3, 139.3, 132.1, 128.8 (d, J = 17.27 Hz, 1C), 127.5, 122.4 (t, J = 254.35 Hz, 1C), 121.4, 81.4 (dd, J = 62.03, 31.13 Hz, 1C), 58.4. 19 19F NMR (282 MHz, CDCl3, 25 °C): -57.81 (d, J = 1.77 Hz, 3F), -76.57 (d, J = 1.32 Hz, 3F). Mass spectrometry: LRMS (ESI-TOF) (m / z): LRMS (ESI-TOF) (m / z): calcd for C 16 H 13 F6O2 + ([M + H] + ), 351.1, found, 351.1.

[0071] The compound synthesized by structural identification was indeed the target compound 4-(2,2,2-trifluoro-1-methoxyethyl)-4'-(trifluoromethoxy)-1,1'-biphenyl.

[0072] Example 6 Method for preparing 3-(4-(2,2,2-trifluoro-1-methoxyethyl)phenyl)thiophene

[0073] Step 1: Add 3-(4-vinylphenyl)thiophene (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until 3-(4-vinylphenyl)thiophene is completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that all of 3-(4-vinylphenyl)thiophene has reacted completely. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry, and pass the petroleum ether through a silica gel column. The product, colorless oil 3-(4-(2,2,2-trifluoro-1-methoxyethyl)phenyl)thiophene, is obtained. Colorless oil (0.025 g, 0.18 mmol, 36% yield); R f = 0.36 (petroleum ether). (See Structure 6b)

[0074]

[0075] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 H NMR (300 MHz, CDCl3, 25 °C,): 7.65 (d, J = 8.31 Hz, 2H), 7.49 (t, J = 2.19 Hz, 1H), 7.45 (s, 1H), 7.41 (d, J = 2.1 Hz, 2H), 4.56 - 4.50 (m, 1H), 3.45 (s, 3H). 13 C NMR (75 MHz, CDCl3, 25 °C,): 141.7, 137.3, 131.3, 128.9, 126.7 (d, J = 10.94 Hz, 1C), 126.4, 122.1 (t, J = 279.98 Hz, 1C), 121.1, 81.4 (dd, J = 30.85, 61.79 Hz, 1C), 58.3. 19 F NMR (282 MHz, CDCl3, 25 °C,): -76.6 (s, 3F). Mass spectrometry: GCMS (ESI-TOF) (m / z): calcd for C 13 H 11F3OS, 272.0, found, 272.0.

[0076] The compound synthesized by structural identification is indeed the target compound 3-(4-(2,2,2-trifluoro-1-methoxyethyl)phenyl)thiophene.

[0077] Method for preparing phenyl 4-(2,2,2-trifluoro-1-methoxyethyl)benzoate in Example 7

[0078] First step: Add phenyl 4-(2,2,2-trifluoro-1-methoxyethyl)benzoate (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction test tube, add 3.0 mL of dried dichloromethane and 1.0 mL of hexafluoroisopropanol, stir until phenyl 4-(2,2,2-trifluoro-1-methoxyethyl)benzoate is completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg), triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) and 1.0 mL of dried methanol to the reaction test tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a battery potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC. Stop the reaction when it is detected that phenyl 4-(2,2,2-trifluoro-1-methoxyethyl)benzoate has completely reacted. The experimental treatment is to drain the solution in the reaction; dissolve the solute in the reaction test tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass the petroleum ether through a silica gel column. Obtain the product phenyl 4-(2,2,2-trifluoro-1-methoxyethyl)benzoate as a white solid. White solid (0.071 g, 0.30 mmol, 60% yield); R f = 0.66 (petroleum ether). (See Structural Formula 7b)

[0079]

[0080] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C): 8.12 (d, J = 7.92 Hz, 2H), 7.60 - 7.55 (m, 1H), 7.44 (t, J = 7.05 Hz, 4H), 7.19 (d, J = 8.67 Hz, 2H), 5.51 - 5.32 (m, 1H), 3.51 (s, 3H). 1313C NMR (75 MHz, CDCl3, 25 °C): 165.1, 152.0, 133.9, 130.4, 130.0, 129.4, 128.8 (d, J = 6.74 Hz, 1C), 122.4 (t, J = 264.59 Hz, 1C), 121.8, 121.1, 91.7 (dd, J = 33.98, 70.04 Hz, 0.5C), 88.8 (dd, J = 36.05, 69.44 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C): -87.1 (dd, J = 12.61, 141.37 Hz, 1F), -89.2 (dd, J = 14.66, 141.56 Hz, 1F), 192.0 (t, J = 13.31 Hz, 1F). Mass spectrometry: HRMS (ESI-TOF) (m / z): calcd for C 16 H 14 F3O3 + ([M+H] + ), 311.0890, found, 311.0891.

[0081] The compound synthesized through structure identification was confirmed to be the target compound phenyl 4-(2,2,2-trifluoro-1-methoxyethyl)benzoate.

[0082] Example 8 Method for preparing 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole

[0083] Step 1: Add 4-(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) into a dry 40 mL reaction tube, add 1-H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4-(2,2-difluoroethyl)-1,1'-biphenyl and 1-H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) into the reaction tube. Stir the whole mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 4-(2,2-difluorovinyl)-1,1'-biphenyl has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it into a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) into the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole. White solid (0.056 g, 0.20 mmol, 40% yield); R f = 0.42 Petroleum ether: Ethyl acetate = 20:1). (See Structural formula 8b)

[0084]

[0085] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C,): δ 7.76 (s, 1H), 7.73 (d, J = 2.1 Hz, 1H), 7.61 (t, J = 2.8 Hz, 1H), 6.47 (t, J = 7.4 Hz, 4H), 7.46 (t, J = 7.1 Hz, 4H), 7.38 (t, J = 7.1 Hz, 1H), 6.50 - 6.28 (m, 2H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 143.0 (d, J = 1.67 Hz, 1C), 142.8, 140.3, 130.1, 129.8, 129.0, 128.4, 127.9 (d, J = 4.59 Hz, 2C), 127.3, 120.1 (t, J = 202.91 Hz, 1C), 107.7, 91.1 (dd, J = 29.91, 64.55 Hz, 0.5C), 88.8 (dd, J = 35.54, 64.55 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -91.8 (dd, J = 207.92, 13.73 Hz, 1F), -97.2 (dd, J = 208.00, 17.94 Hz, 1F), -193.1--193.2 (m, 1F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 17 H 13 F3N2Na + ([M+H] + ), 325.0, found, 325.0.

[0086] The synthesized compound was confirmed to be the target compound 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole by structure identification.

[0087] Example 9 Method for the preparation of 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-fluoro-1H-pyrazole

[0088] Step 1: Add 4-(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 4-fluoro-1H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4-(2,2-difluoroethyl)-1,1'-biphenyl and 4-fluoro-1H-pyrazole are completely dissolved, and then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that all of 4-(2,2-difluorovinyl)-1,1'-biphenyl has reacted completely. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid, 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-fluoro-1H-pyrazole. White solid (0.086 g, 0.29 mmol, 58% yield); R f = 0.35 petroleum ether:ethyl acetate = 20:1). (See Structural formula 9b)

[0089]

[0090] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.62 (t, J = 8.58 Hz, 6H), 7.47 (t, J = 8.31 Hz, 4H), 7.39 (t, J = 7.11 Hz, 1H), 6.45 - 6.23 (m, 1H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 150.3 (d, J = 249.74 Hz, 1C), 141.75 (d, J = 222.03 Hz, 1C), 131.0 (d, J = 14.96 Hz, 1C), 129.8, 129.5, 129.0, 128.0 (d, J = 5.61 Hz, 2C), 127.4 (d, J = 5.61 Hz, 2C), 121.2 (t, J = 277.80 Hz, 1C), 114.3 (d, J = 28.30 Hz, 2C), 90.8 (d, J = 35.95, 27.14 Hz, 0.5C), 88.6 (dd, J = 35.54, 64.55 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -91.1 (dd, J = 208.06, 13.54 Hz, 1F), -98.3 (dd, J = 208.06, 17.96 Hz, 1F), -174.1 (s, 1F), -193.0--193.1 (m, 1F). Mass spectrometry: HRMS (ESI-TOF) (m / z): calcd for C 17 H 12 F4N2Na + ([M + H] + ), 343.0829, found, 343.0829.

[0091] The synthesized compound was confirmed to be the target compound 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-fluoro-1H-pyrazole by structural identification.

[0092] Example 10 Method for preparing 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-bromo-1H-pyrazole

[0093] Step 1: Add 4-(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 4-bromo-1H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4-(2,2-difluoroethyl)-1,1'-biphenyl and 4-bromo-1H-pyrazole are completely dissolved, and then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that all of 4-(2,2-difluorovinyl)-1,1'-biphenyl has reacted completely. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-bromo-1H-pyrazole. White solid (0.062 g, 0.18 mmol, 35% yield); R f = 0.43 petroleum ether: ethyl acetate = 20:1). (See Structural Formula 10b)

[0094]

[0095] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.78 (s, 1H), 7.72 (d, J 0.72 Hz, 1H), 7.61 (t, J = 8.4 Hz, 4H), 7.46 (t, J = 7.2 Hz, 4H), 7.38 (t, J = 7.1 Hz, 1H), 6.42 - 6.21 (m, 1H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 143.4, 143.3 (d, J = 1.64 Hz, 1C), 140.3, 129.6, 129.4, 129.0, 128.5, 128.0 (t, J = 2.83 Hz, 1C), 127.4 (d, J = 6.84 Hz, 2C), 116.7 (t, J = 288.15 Hz, 1C), 96.4, 90.7 (dd, J = 28.07, 64.07 Hz, 0.5C), 88.2 (dd, J = 35.29, 62.84 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -90.6 (dd, J = 208.79, 13.71 Hz, 1F), -98.4 (dd, J = 208.60, 17.60 Hz, 1F), -174.1 (s, 1F), -193.1--193.2 (m, 1F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 17 H 13 BrF3N2 + ([M + H] + ), 381.0, found, 381.0.

[0096] The compound synthesized by structure identification was indeed the target compound 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-bromo-1H-pyrazole.

[0097] Method for preparing 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-chloro-1H-pyrazole in Example 11

[0098] Step 1: Add 4-(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) into a dry 40 mL reaction tube, add 4-chloro-1H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4-(2,2-difluoroethyl)-1,1'-biphenyl and 4-chloro-1H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) into the reaction tube. Stir the whole mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that all of 4-(2,2-difluorovinyl)-1,1'-biphenyl has reacted completely. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it into a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) into the round-bottom flask and spin-dry, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-chloro-1H-pyrazole. White solid (0.048 g, 0.16 mmol, 31% yield); R f = 0.45 Petroleum ether: Ethyl acetate = 20:1). (See Structural formula 11b)

[0099]

[0100] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.74 (s, 1H), 7.69 (d, J 0.69 Hz, 1H), 7.62 (t, J = 8.3 Hz, 4H), 7.46 (t, J = 7.3 Hz, 4H), 7.38 (t, J = 7.1 Hz, 1H), 6.42 - 6.21 (m, 1H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 143.3 (d, J = 1.68 Hz, 1C), 141.4, 140.3, 129.6, 129.4, 129.0, 128.0 (t, J = 3.17 Hz, 1C), 127.4 (d, J = 6.86 Hz, 2C), 126.3, 121.4 (t, J = 163.70 Hz, 1C), 113.1, 90.7 (dd, J = 49.46, 85.61 Hz, 0.5C), 87.6 (dd, J = 36.93, 63.99 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -90.7 (dd, J = 208.62, 17.74 Hz, 1F), -98.4 (dd, J = 208.62, 17.74 Hz, 1F), -193.0--193.2 (m, 1F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 17 H 12 ClF3N2Na + ([M + H] + ), 359.1, found, 359.1.

[0101] The synthesized compound was confirmed to be the target compound 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-chloro-1H-pyrazole by structural identification.

[0102] Example 12 Method for the preparation of 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-iodo-1H-pyrazole

[0103] Step 1: Add 4-(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) into a dry 40 mL reaction tube, add 4-iodo-1H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4-(2,2-difluoroethyl)-1,1'-biphenyl and 4-iodo-1H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) into the reaction tube. Stir the whole mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 4-(2,2-difluorovinyl)-1,1'-biphenyl has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-iodo-1H-pyrazole. White solid (0.050 g, 0.13 mmol, 25% yield); R f = 0.45 Petroleum ether: Ethyl acetate = 20:1). (See Structural formula 12b)

[0104]

[0105] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.81 (s, 1H), 7.76 (s, 1H), 7.61 (t, J = 8.3 Hz, 4H), 7.46 (t, J = 7.1 Hz, 4H), 7.38 (t, J = 7.0 Hz, 1H), 6.42 - 6.21 (m, 1H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 147.6, 143.3, 140.3, 132.8, 129.7, 129.4, 129.0, 128.0 (t, J = 2.90 Hz, 1 C), 127.4 (d, J = 6.25 Hz, 2 C), 120.0 (t, J = 294.36 Hz, 1 C), 91.0 (dd, J = 27.41, 36.41 Hz, 0.5 C), 88.5 (dd, J = 27.29, 36.30 Hz, 0.5 C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -90.4 (dd, J = 208.76, 13.65 Hz, 1 F), -98.3 (dd, J = 208.76, 17.74 Hz, 1 F), -193.0--193.1 (m, 1 F).

[0106] The synthesized compound was confirmed to be the target compound 1-(2-([1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-4-iodo-1H-pyrazole by structural identification.

[0107] Method for preparing 1-(1,1,2-trifluoro-2-(4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)ethyl)-1H-pyrazole in Example 13

[0108] Step 1: Add 4-(2,2-difluorovinyl)-4'-(trifluoromethoxy)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) into a dry 40 mL reaction test tube, add 1-H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4-(2,2-difluorovinyl)-4'-(trifluoromethoxy)-1,1'-biphenyl and 1-H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) into the reaction test tube. Stir the whole mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 4-(2,2-difluorovinyl)-4'-(trifluoromethoxy)-1,1'-biphenyl has completely reacted. The experimental treatment is to drain the solution in the reaction; dissolve the solute in the reaction test tube with petroleum ether and transfer it to a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid 1-(1,1,2-trifluoro-2-(4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)ethyl)-1H-pyrazole. White solid (0.062 g, 0.18 mmol, 35% yield); R f = 0.45 petroleum ether:ethyl acetate = 20:1). (See Structural Formula 13b)

[0109]

[0110] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.77 (s, 1H), 7.73 (d, J = 2.5 Hz, 1H), 7.61 (s, 1H), 7.58 (d, J = 2.3 Hz, 2H), 7.56 (s, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 6.49 - 6.28 (m, 2H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 142.2, 141.4, 139.2, 132.3, 129.9 (t, J = 6.74 Hz, 1C), 129.0, 128.5 (d, J = 2.29 Hz, 1C), 128.2 - 128.1 (m, 1C), 127.5, 127.0, 118.3 (t, J = 259.87 Hz, 1C), 107.1, 82.5 - 81.8 (m, 1C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -57.8 (s, 3F), -91.6 (dd, J = 208.29, 13.65 Hz, 1F), -97.3 (dd, J = 208.29, 17.96 Hz, 1F), -193.5 - -193.6 (m, 1F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 18 H 12 F6KN2O + ([M+K] + ), 425.0, found, 425.0.

[0111] The synthesized compound was confirmed to be the target compound 1-(1,1,2-trifluoro-2-(4'-(trifluoromethoxy)-[1,1'-biphenyl]-4-yl)ethyl)-1H-pyrazole by structural identification.

[0112] Method for preparing 1-(2-(4'-(2,2-difluorovinyl)-[1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole in Example 14

[0113] Step 1: Add 4,4'-bis(2,2-difluorovinyl)-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 1-H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4,4'-bis(2,2-difluorovinyl)-1,1'-biphenyl and 1-H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 4,4'-bis(2,2-difluorovinyl)-1,1'-biphenyl has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid 1-(2-(4'-(2,2-difluorovinyl)-[1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole. White solid (0.059 g, 0.23 mmol, 45% yield); R f = 0.41 petroleum ether: ethyl acetate = 20:1). (See Structural Formula 14b)

[0114]

[0115] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.75 (d, J = 11.4 Hz, 2H), 7.64 - 7.60 (m, 4H), 7.55 (d, J = 8.1 Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.50 - 6.28 (m, 2H), 5.73 - 85.56 (m, 1H). 13CNMR(75MHz,CDCl3,25℃,δ):142.8,142.5(d,J=1.46Hz,1C),141.8(d,J=1.00Hz,1C),130.9(d,J=1.64Hz,1C),130.6(d,J=1.56Hz,1C),130.5,129.9(d,J=1.58Hz,1C),129.7,128.4,128.1(d,J=6.71Hz,1C),127.9(d,J=6.70Hz,1C),127.5(d,J=17.63Hz,1C),120.0(t,J=267.32Hz,1C),107.8,91.6 - 86.9(m,1C). 19 FNMR(282MHz,CDCl3,25℃,δ): - 78.6(s,2F), - 91.7(dd,J=208.17,13.54Hz,1F), - 97.2(dd,J=208.17,17.96Hz,1F), - 193.5 - - 194.5(m,1F). Mass spectrometry: LRMS(ESI - TOF)(m / z): calcd for C 19 H 14 F5N2 + ([M + H] + ),365.1,found,365.1

[0116] The compound synthesized through structure identification is indeed the target compound 1 - (2 - (4' - (2,2 - difluorovinyl)-[1,1'-biphenyl]-4 - yl)-1,1,2 - trifluoroethyl)-1H - pyrazole.

[0117] Method for preparing 1 - (2 - (3',5' - difluoro - [1,1'-biphenyl]-4 - yl)-1,1,2 - trifluoroethyl)-1H - pyrazole in Example 15

[0118] Step 1: Add 4'-(2,2-difluorovinyl)-3,5-difluoro-1,1'-biphenyl (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 1-H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 4'-(2,2-difluorovinyl)-3,5-difluoro-1,1'-biphenyl and 1-H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that all of 4'-(2,2-difluorovinyl)-3,5-difluoro-1,1'-biphenyl has reacted completely. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid, 1-(2-(3',5'-difluoro-[1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole. White solid (0.040 g, 0.15 mmol, 30% yield); R f = 0.41 petroleum ether:ethyl acetate = 20:1). (See Structural Formula 15b)

[0119]

[0120] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.77 - 7.73 (m, 2H), 7.56 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 7.11 - 7.08 (m, 2H), 6.85 - 6.77 (m, 1H), 6.50 - 6.29 (m, 2H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 165.1 (d, J = 12.87 Hz, 1C), 161.8 (d, J = 13.02 Hz, 1C), 143.6 (t, J = 9.56 Hz, 1C), 142.8, 140.6, 131.3 (d, J = 22.01 Hz, 1C), 128.4, 128.2 (d, J = 6.71 Hz, 1C), 127.2, 120.3 (t, J = 254.49 Hz, 1C), 110.2 (m, 1C), 107.8, 103.2 (d, J = 25.24 Hz, 1C), 91.0 (dd, J = 35.65, 28.07 Hz, 0.5C), 88.5 (dd, J = 35.75, 28.07 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -91.8 (dd, J = 208.12, 13.56 Hz, 1F), -96.9 (dd, J = 208.14, 17.96 Hz, 1F), -100.3 (s, 2F), -193.9--194.0 (m, 1F). Mass spectrometry: HRMS (ESI-TOF) (m / z): calcd for C 17 H 12 F5N2 + ([M + H] + ), 339.0915, found, 339.0917.

[0121] The synthesized compound was confirmed to be the target compound 1-(2-(3',5'-difluoro-[1,1'-biphenyl]-4-yl)-1,1,2-trifluoroethyl)-1H-pyrazole by structure identification.

[0122] Method for preparing 1-(1,1,2-trifluoro-2-(4-(thiophen-3-yl)phenyl)ethyl)-1H-pyrazole in Example 16

[0123] Step 1: Add 3-(4-(2,2-difluorovinyl)phenyl)thiophene (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 1-H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 3-(4-(2,2-difluorovinyl)phenyl)thiophene and 1-H-pyrazole are completely dissolved, and then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that 3-(4-(2,2-difluorovinyl)phenyl)thiophene has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a white solid, 1-(1,1,2-trifluoro-2-(4-(thiophen-3-yl)phenyl)ethyl)-1H-pyrazole. White solid (0.040 g, 0.15 mmol, 30% yield); R f = 0.41 petroleum ether:ethyl acetate = 20:1). (See Structural Formula 16b)

[0124]

[0125] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 1H NMR (300 MHz, CDCl3, 25 °C, δ): 7.76 (d, J = 1.1 Hz, 1H), 7.71 (d, J = 2.0 Hz, 2H), 7.61 (d, J = 8.0 Hz, 2H), 7.50 - 7.48 (m, 1H), 7.42 - 7.39 (m, 4H), 6.44 - 6.23 (m, 2H). 13 13C NMR (75 MHz, CDCl3, 25 °C, δ): 142.8, 141.5, 137.6, 129.6, 128.4, 128.0 (d, J = 6.74 Hz, 1C), 126.7, 126.6, 126.3, 121.3, 118.3 (t, J = 210.50 Hz, 1C), 107.8, 91.5 (dd, J = 26.41, 60.47 Hz, 0.5C), 90.0 (dd, J = 33.53, 68.83 Hz, 0.5C).19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -92.3 (dd, J = 207.75, 13.79 Hz, 1 F), -96.9 (dd, J = 207.89, 18.22 Hz, 1 F), -100.3 (s, 2 F), -193.2 - 194.3 (m, 1 F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 15 H 11 F3N2NaS + ([M + H] + ), 331.0, found, 331.0.

[0126] The synthesized compound was confirmed to be the target compound 1-(1,1,2-trifluoro-2-(4-(thiophen-3-yl)phenyl)ethyl)-1H-pyrazole by structure identification.

[0127] Example 17 Method for the preparation of phenyl 4-(1,2,2-trifluoro-2-(1H-pyrazol-1-yl)ethyl)benzoate

[0128] First step: Add phenyl 4-(2,2-difluorovinyl)benzoate (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 1-H-pyrazole 2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until phenyl 4-(2,2-difluorovinyl)benzoate and 1-H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that phenyl 4-(2,2-difluorovinyl)benzoate has completely reacted. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask. Add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry it, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product phenyl 4-(1,2,2-trifluoro-2-(1H-pyrazol-1-yl)ethyl)benzoate as a white solid. White solid (0.061 g, 0.23 mmol, 45% yield); R f = 0.48 Petroleum ether: Ethyl acetate = 20:1). (See Structure 17b)

[0129]

[0130] The structural confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 H NMR (300 MHz, CDCl3, 25 °C, δ): 8.05 (d, J = 7.38 Hz, 2H), 7.59 (d, J = 12.39 Hz, 1H), 7.51 (t, J = 7.29 Hz, 1H), 7.37 (t, J = 7.83 Hz, 2H), 7.31 (d, J = 8.46 Hz, 2H), 7.12 (d, J = 2.67 Hz, 1H), 7.09 (s, 2H), 6.32 - 6.11 (m, 2H). 13 C NMR (75 MHz, CDCl3, 25 °C, δ): 165.0, 152.3, 142.8, 133.9, 130.3, 129.4, 128.8 (d, J = 6.87 Hz, 1C), 128.5 (d, J = 2.04 Hz, 1C), 128.4, 122.0, 119.9 (t, J = 305.24 Hz, 1C), 107.8, 90.9 (dd, J = 28.29, 35.42 Hz, 0.5C), 88.4 (dd, J = 27.50, 34.52 Hz, 0.5C). 19 F NMR (282 MHz, CDCl3, 25 °C, δ): -92.5 (dd, J = 13.08, 207.83 Hz, 1F), -96.8 (dd, J = 17.82, 207.81 Hz, 1F), -193.0 - -193.1 (m, 1F). Mass spectrometry: HRMS (ESI-TOF) (m / z): calcd for C 18 H 14 F3N2O2 + ([M + H] + ), 347.1002, found, 347.1000.

[0131] The synthesized compound was structurally identified as the target compound phenyl 4-(1,2,2-trifluoro-2-(1H-pyrazol-1-yl)ethyl)benzoate.

[0132] Method for preparing 1-(1,1,2-trifluoro-2-(4-phenylthiophen-2-yl)ethyl)-1H-pyrazole in Example 18

[0133] Step 1: Add 2-(2,2-difluorovinyl)-4-phenylthiophene (0.5 mmol, 108 mg, 1.0 equiv) to a dry 40 mL reaction tube, add 1-H-pyrazole (2 mmol, 136 mg, 4.0 eq.), add 4.0 mL of dried dichloromethane, stir until 2-(2,2-difluorovinyl)-4-phenylthiophene and 1-H-pyrazole are completely dissolved, then add tetrabutylammonium tetrafluoroborate (0.5 mmol, 1.0 eq., 165 mg) and triethylamine hydrogen fluoride (0.5 mmol, 80 mg, 1.0 equiv) to the reaction tube. Stir the entire mixture in air at room temperature with a carbon plate (2.0 cm × 1.0 cm × 2.0 mm) as the anode and a platinum plate electrode (1.5 cm × 1.5 cm × 0.1 mm) as the cathode, and stir and electrolyze the reaction mixture at a cell potential of 3.5 V at room temperature. Monitor the progress of the reaction by TLC, and stop the reaction when it is detected that all of 2-(2,2-difluorovinyl)-4-phenylthiophene has reacted completely. The experimental treatment is to dry the solution in the reaction; dissolve the solute in the reaction tube with petroleum ether and transfer it to a 100 mL round-bottom flask, add 2 mL of silica gel (200 - 300 mesh) to the round-bottom flask and spin-dry, and pass through a silica gel column with petroleum ether / ethyl acetate. Obtain the product as a colorless oil, 1-(1,1,2-trifluoro-2-(4-phenylthiophen-2-yl)ethyl)-1H-pyrazole. Colorless oil (0.025 g, 0.09 mmol, 18% yield); R f = 0.48 petroleum ether:ethyl acetate = 20:1). (See Structural formula 12b)

[0134]

[0135] Structure confirmation is as follows: Nuclear magnetic resonance spectroscopy: 1 H NMR (300 MHz, CDCl3, 25 °C, δ): 7.78 (d, J = 15.06 Hz, 2H), 7.53 (d, J = 6.96 Hz, 3H), 7.45 - 7.37 (m, 3H), 7.30 (t, J = 7.14 Hz, 1H), 6.69 (t, J = 8.58 Hz, 0.5H), 6.54 (t, J = 10.71 Hz, 0.5H), 6.41 (s, 1H). 1313C NMR (75 MHz, CDCl3, 25 °C, δ): 142.9, 142.3, 135.2, 129.1, 128.9 (d, J = 5.42 Hz, 1C), 128.4, 127.7, 126.5, 123.2 (d, J = 2.18 Hz, 1C), 128.0, 120.1 (t, J = 272.36 Hz, 1C), 88.2 (dd, J = 38.57, 74.69 Hz, 0.5C), 85.2 (dd, J = 38.57, 74.69 Hz, 0.5C). 19 19F NMR (282 MHz, CDCl3, 25 °C, δ): -92.1 (dd, J = 36.94, 65.66 Hz, 1F), -95.8 (dd, J = 18.70, 206.34 Hz, 1F), -179.5--179.6 (m, 1F). Mass spectrometry: LRMS (ESI-TOF) (m / z): calcd for C 15 H 11 F3N2NaS + ([M+H] + ), 331.0, found, 331.1.

[0136] The synthesized compound was confirmed to be the target compound 1-(1,1,2-trifluoro-2-(4-phenylthiophen-2-yl)ethyl)-1H-pyrazole by structure identification.

Claims

1. A reaction method for the selective fluorination functionalization of gem-difluoroolefins, characterized in that, With gem-difluoroolefin, hydrogen fluoride triethylamine and a nucleophile as raw materials, an organic solvent is added for an electrochemical reaction to obtain a fluorinated product at the 1-position or 2-position of the gem-difluoroolefin; Among them, the gem-difluoroolefin has a structural formula as shown in Formula I; the fluorinated product at the 1-position of the gem-difluoroolefin is as shown in Formula V; the fluorinated product at the 2-position of the gem-difluoroolefin is as shown in Formula VI; R1 in Formula I, Formula V and Formula VI is selected from any one of the following groups: phenyl, (trifluoromethoxy)phenyl, (2,2-difluorovinyl)phenyl, 1,3-difluorophenyl, thiophenyl, benzoic acid group; Formula I; Formula V; Formula VI; R2 in Formula VI is selected from any one of the following groups: fluorine, chlorine, bromine, iodine; The specific reaction method for the fluorinated product at the 1-position of the gem-difluoroolefin is: Step (1a): Dissolve the gem-difluoroolefin in an organic solvent, then add tetrabutylammonium tetrafluoroborate, hydrogen fluoride triethylamine and methanol to obtain a reaction raw material mixture; Step (2a): Stir the reaction raw material mixture in air at room temperature, and carry out an electrolysis reaction with a carbon plate as the anode and a platinum plate electrode as the cathode; after the reaction is completed, the product is separated and purified to obtain the fluorinated product at the 1-position of the gem-difluoroolefin; In Step (2a), the voltage of the electrolysis reaction is 3 - 4V, and the time of the electrolysis reaction is 3 - 5h; The specific reaction method for the fluorinated product at the 2-position of the gem-difluoroolefin is: Step (1b): Dissolve the gem-difluoroolefin in an organic solvent, then add tetrabutylammonium tetrafluoroborate, hydrogen fluoride triethylamine and a pyrazole compound to obtain a reaction raw material mixture; Step (2b): Stir the reaction raw material mixture in air at room temperature, and carry out an electrolysis reaction with a carbon plate as the anode and a platinum plate electrode as the cathode; after the reaction is completed, the product is separated and purified to obtain the fluorinated product at the 2-position of the gem-difluoroolefin; In Step (2b), the voltage of the electrolysis reaction is 3 - 4V, and the time of the electrolysis reaction is 3 - 5h; The pyrazole compound has a structural formula as shown in Formula IV; Among them, R2 in Formula IV is selected from any one of the following groups: fluorine, chlorine, bromine, iodine. Formula IV; The organic solvent in Step (1a) is composed of dichloromethane and hexafluoroisopropanol.

2. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 1, wherein The volume ratio of the dichloromethane to the hexafluoroisopropanol is 2 - 4:

1.

3. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 2, wherein In Step (1a), the dosage ratio of tetrabutylammonium tetrafluoroborate to hydrogen fluoride triethylamine and methanol is 0.1 - 0.2g:1 - 2mL:1 - 2mL.

4. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 1, characterized in that, In Step (2a), the voltage of the electrolysis reaction is 3.5V, and the time of the electrolysis reaction is 4h.

5. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 1, characterized in that, The organic solvent in Step (1b) is dichloromethane.

6. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 1, characterized in that, In Step (1b), the dosage ratio of tetrabutylammonium tetrafluoroborate to hydrogen fluoride triethylamine is 0.1 - 0.2g:1 - 2mL; 7. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 1, wherein In Step (1b), the molar ratio of the gem-difluoroolefin to tetrabutylammonium tetrafluoroborate is 1:

1. In Step (2b), the voltage of the electrolysis reaction is 3.5V, and the time of the electrolysis reaction is 4h.

8. The reaction method for the selective fluorination functionalization of gem-difluoroolefins according to claim 1, characterized in that, ​

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