A method for synthesizing 2-substituted-3-trifluoromethylselenoindole compounds

Abstract

The application discloses a synthesis method of a 2-substituted-3-trifluoromethylselenyl indole compound. The method uses a 2-trifluoromethylselenyl acetylene aniline derivative as a substrate, diethyl zinc as an alkali, a zinc salt as a promoter, and performs a reaction in a solvent, and then adds an electrophilic reagent to synthesize the 2-substituted-3-trifluoromethylselenyl indole compound. The synthesis method has the advantages of simple operation, diversified products, and one-pot high-efficiency synthesis of products which are not easy to obtain by other methods.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic fluorine chemical synthesis, and particularly relates to a synthesis method of 2-substituted-3-trifluoromethylselenoindole compounds. BACKGROUND

[0002] Indole is an important class of heterocyclic compounds, which is widely present in some bioactive molecules, lead compounds and drug molecules. The introduction of fluorine-containing groups into indole molecules can change their physicochemical properties. Trifluoromethylseleno group contains fluorine and selenium, has unique stereo and electronic effects and strong liposolubility. The introduction of trifluoromethylseleno group into indole ring has been proved to be able to enhance its biological activity. At present, the method for synthesizing trifluoromethylselenoindole compounds mainly introduces trifluoromethylseleno group into the existing indole skeleton, which is limited in the synthesis of substrates and is not conducive to the extensive biological activity screening. The application reports a migration reaction of trifluoromethylseleno group under the promotion of zinc to prepare 2-substituted-3-trifluoromethylselenoindole compounds. SUMMARY

[0003] The application aims to provide a synthesis method of 2-substituted-3-trifluoromethylselenoindole compounds, which has the advantages of simple operation, diversified products, one-pot high-efficiency synthesis of products that are not easy to obtain by other methods and the like.

[0004] To achieve the above-mentioned purpose, the application adopts the following technical scheme:

[0005] A synthesis method of 2-substituted-3-trifluoromethylselenoindole compounds, which is to use 2-trifluoromethylselenoacetylene aniline derivatives as substrates, diethyl zinc as a base, zinc salt as a promoter, and then perform a reaction in a solvent, and then add an electrophilic reagent to synthesize 2-substituted-3-trifluoromethylselenoindole compounds.

[0006] The 2-trifluoromethylselenoacetylene aniline derivatives are any one of the following formula 1 to formula 16 (Ts = p-toluenesulfonyl):

[0007]

[0008] The zinc salt is one of ZnCl2, ZnI2 and ZnBr2.

[0009] The electrophilic reagent is one of N-bromosuccinimide (NBS), N-iodosuccinimide (NIS), water, deuterium water, deuterium iodomethane and benzoyl chloride.

[0010] The use of N-bromosuccinimide (NBS) as an electrophilic reagent to obtain 2-bromo-3-trifluoromethylselenoindole compounds is any one of the following formula 1 to formula 16 (Ts = p-toluenesulfonyl):

[0011]

[0012] The 2-iodo-3-trifluoromethylselenoindole compound is obtained by using N-iodosuccinimide (NIS) as an electrophile, and specifically any one of the following formula 1 to formula 16 (Ts = p-toluenesulfonyl):

[0013]

[0014] The 2-substituted-3-trifluoromethylselenoindole compound is obtained by using other electrophiles, such as water, deuterium water, deuterium iodomethane, and benzoyl chloride, and specifically any one of the following formula 1 to formula 4 (Ts = p-toluenesulfonyl):

[0015]

[0016] Further, the synthesis method of the 3-acetylamino trifluoromethyl benzene compound is as follows: 2-trifluoromethylseleno acetylene aniline derivative, diethyl zinc and zinc salt are mixed in a solvent, under magnetic stirring, after reaction at 110-150 DEG C for 2-6h, then an electrophile is added, and after reaction at room temperature for 1-4h, the reaction mixture is diluted with ethyl acetate, washed with saturated sodium bicarbonate solution, and the obtained organic phase is dried over anhydrous MgSO4, filtered and rotary evaporated to remove the solvent, and then purified by silica gel column to obtain the 2-substituted-3-trifluoromethylselenoindole compound.

[0017] In the method, the molar ratio of the 2-trifluoromethylseleno acetylene aniline derivative, diethyl zinc, zinc salt and electrophile is (0.2-1):(1-10):(0.6-5):(0.6-5).

[0018] The present application has the following advantages:

[0019] The present application uses simple and easily available 2-trifluoromethylseleno acetylene aniline derivative as a substrate, diethyl zinc as a base, zinc salt as a promoter, and then reacts with an electrophile to synthesize 2-substituted-3-trifluoromethylselenoindole compound, which has good adaptability of functional groups, and has the advantages of simple operation, product diversification, one-pot high-efficiency synthesis of products not easily obtained by other methods, etc. The prepared 2-substituted-3-trifluoromethylselenoindole compound has good control effect on pine wood nematode. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The flow chart for synthesizing 2-substituted-3-trifluoromethylselenoindole compound of the present application, wherein Ts = p-toluenesulfonyl; E = electrophile.

[0021] Figure 2A single crystal structure of 2-bromo-1 -toluenesulfonyl-3-trifluoromethylseleno-1 H- indole prepared for Example 1. DETAILED DESCRIPTION

[0022] In order to make the content of the present application more convenient to understand, the technical solutions described in the present application will be further described below in combination with specific embodiments, but the present application is not limited thereto.

[0023] Substrate Formula 1 : CAS No. 2761259-47-4.

[0024] Substrate Formula 2

[0025]

[0026] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(2-ethynyl-4-methylphenyl)-4-methylbenzenesulfonamide (CAS: 930282-16-9), 2.8 mmol of copper trifluoromethylselenolate bispyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride were added, and finally 20 mL of anhydrous acetonitrile solvent was added. The reaction was stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, the mixture was diluted with 20 mL of deionized water, and the solution was extracted with 3x15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, and the obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 4-methyl-N-(4-methyl-2-(trifluoromethyl)seleno)ethynyl)phenyl benzenesulfonamide was separated by silica gel column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluent (isolation yield 33%), and its characterization data were as follows: 1 HNMR (400 MHz, CDC13) δ 7.62 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.2 Hz, 1H), 7.20 (d, J = 8.1 Hz, 2H), 7.16 - 7.10 (m, 2H), 6.97 (s, 1H), 2.36 (s, 3H), 2.24 (s, 3H). 19 FNMR (376 MHz, CDC13) δ -35.7 (s, 3F). 13C NMR (101 MHz, CDC13) δ 144.0 (s), 135.9 (s), 135.8 (s), 134.7 (s), 133.1 (s), 131.9 (s), 129.6 (s), 127.2 (s), 121.2 (s), 120.5 (q, J = 336.8 Hz), 113.6 (s), 102.1 (s), 68.4 (q, J = 3.1 Hz), 21.5 (s), 20.5 (s)

[0027] Substrate Formula 3

[0028]

[0029] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(2-ethynyl-5-methylphenyl)-4-methylbenzenesulfonamide (CAS: 1184944-70-4), 2.8 mmol of copper selenolate triflate complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added, stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3 x 15 mL of ethyl acetate, and the organic phase was washed with 10.0 mL of saturated sodium chloride solution. The obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 4-methyl-N-(5-methyl-2-(trifluoromethyl)seleno)ethynyl)phenylbenzenesulfonamide, was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (20: 1, v / v) as the eluent (isolation yield 29%), and its characterization data were as follows: 1 H NMR (400 MHz, CDC13) δ 7.62 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.19 (d, J = 8.1 Hz, 2H), 7.16 - 7.10 (m, 2H), 6.99 (s, 1H), 2.36 (s, 3H), 2.24 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.7. 13 C NMR (101 MHz, CDC13) δ 144.1 (s), 135.9 (s), 135.8 (s), 134.7 (s), 133.1 (s), 131.9 (s), 129.6 (s), 127.2 (s), 121.3 (s), 120.5 (q, J = 336.8 Hz), 113.6 (s), 102.1 (s), 68.5 (q, J = 3.0 Hz), 21.5 (s), 20.5 (s)

[0030] Substrate Formula 4

[0031]

[0032] In a 10 mL reaction tube equipped with a magnetic stir bar of Teflon, 2.0 mmol of methyl 2-(3-ethynyl-4-((4-methylphenyl)sulfonamido)phenyl)acetate (CAS: 2889432-31-7), 2.8 mmol of copper selenotri fluoride dipyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added, stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3x15 mL of ethyl acetate, and the organic phase was washed with 10.0 mL of saturated sodium chloride solution. The obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Methyl 2-(4-(4-methylphenyl)sulfonamido)-3-((trifluoromethyl)seleno)ethynyl)phenyl)acetate was obtained by silica gel column chromatography with petroleum ether and ethyl acetate (20:1, v / v) as eluent (isolation yield 45%), and its characterization data were as follows: 1 HNMR (400 MHz, CDC13) δ 7.65 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 8.3 Hz, 1H), 7.30 - 7.23 (m, 2H), 7.21 (d, J = 8.1 Hz, 2H), 7.14 (s, 1H), 3.68 (s, 3H), 3.52 (s, 2H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.6. (s, 3F). 13 C NMR (101 MHz, CDC13) δ 171.3 (s), 144.2 (s), 137.5 (s), 135.9 (s), 133.5 (s), 132.1 (s), 130.5 (s), 129.7 (s), 127.2 (s), 120.7 (s), 120.5 (q, J = 336.9 Hz), 113.4 (s), 101.6 (s), 69.4 (q, J = 3.2 Hz), 52.2 (s), 39.9 (s), 21.5 (s)

[0033] Substrate Formula 5

[0034]

[0035] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(4- ethyl-2-ethynylphenyl)-4-methylbenzenesulfonamide (CAS: 2761259-48-5), 2.8 mmol of copper selenolate triflate [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added. The reaction was stirred at room temperature under air for 10-30 min, and the progress of the reaction was followed by TLC. After the completion of the reaction, the reaction mixture was diluted with 20 mL of deionized water and the mixture was extracted with 3 x 15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, N-(4-ethyl-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4- methylbenzenesulfonamide, was isolated by column chromatography on silica gel using petroleum ether and ethyl acetate (20: 1, v / v) as eluent (isolated yield 37%) and characterized by: 1 HNMR (400 MHz, CDC13) δ 7.63 (d, J = 8.3 Hz, 2H), 7.56 (d, J = 8.2 Hz, 1H), 7.25 - 7.13 (m, 4H), 6.96 (s, 1H), 2.55 (q, J = 7.6 Hz, 2H), 2.36 (s, 3H), 1.17 (t, J = 7.6 Hz, 3H). 19 F NMR (376 MHz, CDC13) δ -35.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.0 (s), 140.9 (s), 136.1 (s), 135.9 (s), 132.0 (s), 130.8 (s), 129.6 (s), 127.2 (s), 121.2 (s), 120.5 (q, J = 336.8 Hz), 113.5 (s), 102.3 (s), 68.4 (q, J = 3.1 Hz), 27.9 (s), 21.5 (s), 15.1 (s)

[0036] Substrate Formula 6

[0037]

[0038] In a 10 mL reaction tube equipped with a magnetic stir bar of polytetrafluoroethylene, 2.0 mmol of N-(4-tert-butyl)-2-ethynylphenyl-4-methylbenzenesulfonamide (CAS: 2761259-49-6), 2.8 mmol of copper selenotri fluoride dipyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added, stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3x15 mL of ethyl acetate, and the organic phase was washed with 10.0 mL of saturated sodium chloride solution. The obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. N-(4-tert-butyl)-2-(trifluoromethyl)selenyl)ethynyl)phenyl)-4-methylbenzenesulfonamide was obtained by silica gel column chromatography separation with petroleum ether and ethyl acetate (20:1, v / v) as eluent (isolation yield 31%), and its characterization data were: 1 HNMR (400 MHz, CDC13) δ 7.66 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.6 Hz, 1H), 7.40 - 7.35 (m, 1H), 7.34 (d, J = 2.3 Hz, 1H), 7.21 (d, J = 8.2 Hz, 2H), 7.03 (s, 1H), 2.37 (s, 3H), 1.25 (s, 9H). 19 F NMR (376 MHz, CDC13) δ -35.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 147.8 (s), 144.0 (s), 136.1 (s), 136.0 (s), 129.7 (s), 129.6 (s), 128.5 (s), 127.2 (s), 120.6 (q, J = 336.8 Hz), 120.5 (s), 112.9 (s), 102.5 (s), 68.2 (q, J = 3.0 Hz), 34.3 (s), 31.0 (s), 21.5 (s)

[0039] Substrate Formula 7

[0040]

[0041] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(3-ethynyl-[l,l'-biphenyl]-4-yl)-4-methylbenzenesulfonamide, 2.8 mmol of trifluoromethylselenolate copper complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added. The reaction mixture was stirred at room temperature under air for 10-30 min, and the progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was diluted with 20 mL of deionized water and the combined solution was extracted with 3 x 15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 4-methyl-N-(3-(trifluoromethyl)seleno)ethynyl)-[l,l'-biphenyl]-4-yl)benzenesulfonamide, was isolated in 35% yield by silica gel column chromatography using petroleum ether and ethyl acetate (20: 1, v / v) as eluents. The characterization data for the product were: 1 H NMR (400 MHz, CDC13) δ 7.74 - 7.66 (m, 3H), 7.58 - 7.52 (m, 2H), 7.46 (d, J = 7.1 Hz, 2H), 7.39 (t, J = 7.6 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 7.24 - 7.17 (m, 3H), 2.35 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.5 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.3 (s), 138.8 (s), 137.7 (s), 137.6 (s), 135.9 (s), 131.2 (s), 129.7 (s), 129.6 (s), 128.9 (s), 127.8 (s), 127.3 (s), 126.7 (s), 122.2 (q, J = 338.3 Hz), 121.0 (s), 113.8 (s), 101.9 (s), 69.4 (q, J = 3.2 Hz), 21.5 (s)

[0042] Substrate Formula 8

[0043]

[0044] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(2-ethynyl-4-methoxyphenyl)-4-methylbenzenesulfonamide (CAS: 1616974-98-1), 2.8 mmol of copper selenolate triflate complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added. The reaction was stirred at room temperature in air for 10-30 min, and the progress of the reaction was followed by TLC. After the completion of the reaction, the reaction mixture was diluted with 20 mL of deionized water and the mixture was extracted with 3 x 15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, N-(4-methoxy-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide, was isolated by column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluents (51% isolated yield) and characterized by the following data: 1 H NMR (400 MHz, CDC13) δ 7.60 - 7.52 (m, 3H), 7.19 (d, J = 8.1 Hz, 2H), 6.97 - 6.88 (m, 1H), 6.84 - 6.74 (m, 2H), 3.75 (s, 3H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.5 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 156.8 (s), 144.0 (s), 135.8 (s), 131.3 (s), 127.2 (s), 124.6 (s), 120.5 (q, J = 336.8 Hz), 117.6 (s), 116.7 (s), 115.9 (s), 102.0 (s), 68.4 (q, J = 3.2 Hz), 55.5 (s), 21.5 (s)

[0045] Substrate Formula 9

[0046]

[0047] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of 4-ethynyl-3-((4-methylphenyl)sulfonylamido)benzoic acid methyl ester (CAS: 930282-14-7), 2.8 mmol of copper selenotri fluoride dipyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added, stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3 x 15 mL of ethyl acetate, and the organic phase was washed with 10.0 mL of saturated sodium chloride solution. The obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Methyl 4-(4-methylphenyl)sulfonylamido)-3-((trifluoromethyl)seleno)ethynyl)benzoate was obtained by silica gel column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluent (isolation yield 45%), and its characterization data were as follows: 1 H NMR (400 MHz, CDC13) δ 8.28 (d, J = 1.5 Hz, 1H), 7.76 - 7.71 (m, 1H), 7.68 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.2 Hz, 1H), 7.23 (d, J = 7.7 Hz, 2H), 7.17 (s, 1H), 3.94 (s, 3H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.1 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 165.7 (s), 144.5 (s), 138.4 (s), 135.6 (s), 132.5 (s), 132.1 (s), 129.7 (s), 127.3 (s), 125.4 (s), 121.2 (s), 120.5 (q, J = 337.0 Hz), 117.3 (s), 101.2 (s), 72.2 (q, J = 3.1 Hz), 52.6 (s), 21.5 (s)

[0048] Substrate Formula 10

[0049]

[0050] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(2-ethynyl-4-trifluoromethylphenyl)-4-methylbenzenesulfonamide (CAS: 1186610-43-4), 2.8 mmol of copper selenolate triflate [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added. The reaction was stirred at room temperature under air for 10-30 min, and the progress of the reaction was followed by TLC. After the completion of the reaction, the reaction mixture was diluted with 20 mL of deionized water and the mixture was extracted with 3 x 15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 4-methyl-N-(4-trifluoromethyl)-2-(trifluoromethyl)seleno)ethynyl)phenyl)benzenesulfonamide, was isolated in 47% yield by silica gel column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluents, and characterized by the following data: 1 HNMR (400 MHz, CDC13) δ 7.78 - 7.68 (m, 3H), 7.61 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.38 (s, 1H), 7.27 (d, J = 7.8 Hz, 2H), 2.39 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.2 (s, 3F), -62.5 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.8 (s), 141.4 (s), 135.5 (s), 130.0 (s), 129.9 (s), 127.7 (q, J = 3.6 Hz), 127.2 (s), 126.3 (q, J = 33.7 Hz), 123.2 (q, J = 272.1 Hz), 120.5 (q, J = 336.9 Hz), 118.9 (s), 112.5 (s), 100.3 (s), 71.6 (q, J = 3.0 Hz), 21.5 (s)

[0051] Substrate Formula 11

[0052]

[0053] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(2-ethynyl-4-fluorophenyl)-4-methylbenzenesulfonamide (CAS: 1616974-99-2), 2.8 mmol of copper selenotri fluoride dipyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added, stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3 x 15 mL of ethyl acetate, and the organic phase was washed with 10.0 mL of saturated sodium chloride solution. The obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. N-(4-fluoro-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide was obtained by silica gel column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluent (32% isolated yield), and its characterization data were as follows: 1 H NMR (400 MHz, CDC13) δ 7.64 (dd, J = 9.1, 5.0 Hz, 1H), 7.60 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.1 Hz, 2H), 7.12 - 7.04 (m, 1H), 7.04 - 6.96 (m, 2H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.2 (s, 3F), -116.1 - -116.2 (m, IF). 13 C NMR (101 MHz, CDC13) δ 159.2 (d, J = 246.7 Hz), 144.3 (s), 135.6 (s), 134.5 (d, J = 3.0 Hz), 129.7 (s), 127.2 (s), 123.9 (d, J = 8.6 Hz), 120.5 (q, J = 336.9 Hz), 118.9 (d, J = 24.4 Hz), 118.3 (d, J = 22.7 Hz), 115.7 (d, J = 9.8 Hz), 100.8 (d, J = 2.9 Hz), 70.2 (q, J = 3.2 Hz), 21.5 (s)

[0054] Substrate Formula 12

[0055]

[0056] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(2-ethynyl-5-fluorophenyl)-4-methylbenzenesulfonamide (CAS: 2195360-42-8), 2.8 mmol of copper selenotri fluoride bispyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added, stirred at room temperature in air for 10-30 min, and the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3 x 15 mL of ethyl acetate, and the organic phase was washed with 10.0 mL of saturated sodium chloride solution. The obtained organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. N-(5-fluoro-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide was obtained by silica gel column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluent (isolation yield 42%), and its characterization data were as follows: 1 HNMR (400 MHz, CDC13) δ 7.70 (d, J = 8.2 Hz, 2H), 7.40 (dd, J = 10.3, 2.6 Hz, 1H), 7.33 (dd, J = 8.7, 6.0 Hz, 1H), 7.28 - 7.20 (m, 3H), 6.75 (td, J = 8.2, 2.5 Hz, 1H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.6 (s, 3F), -104.0 - -104.1 (m, 1F). 13 CNMR (101 MHz, CDC13) δ 163.8 (d, J = 252.7 Hz), 144.6 (s), 140.7 (d, J = 11.8 Hz), 135.6 (s), 134.7 (d, J = 10.0 Hz), 129.8 (s), 127.2 (s), 120.5 (q, J = 337.0 Hz), 111.8 (d, J = 22.7 Hz), 108.5 (d, J = 3.3 Hz), 107.3 (d, J = 27.5 Hz), 100.9 (s), 69.5 (q, J = 3.2 Hz), 21.5 (s)

[0057] Substrate Formula 13

[0058]

[0059] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(5-chloro-2-ethynylphenyl)-4-methylbenzenesulfonamide (CAS: 1616975-04-2), 2.8 mmol of copper selenotri fluoride bispyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride were added, finally 20 mL of anhydrous acetonitrile solvent was added, stirred at room temperature in air for 10-30 min, the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3x15 mL of ethyl acetate, the organic phase was washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgS04, filtered and the solvent was removed by rotary evaporation, and N-(5-chloro-2-(trifluoromethyl)selenyl)ethynyl)phenyl)-4-methylbenzenesulfonamide was obtained by silica gel column chromatography separation (isolation yield 41%) with petroleum ether and ethyl acetate (20: 1, v / v) as eluent, and its characterization data were: 1 HNMR (400 MHz, CDC13) δ 7.78 - 7.63 (m, 3H), 7.32 - 7.20 (m, 3H), 7.19 (s, 1H), 7.02 (d, J = 7.5 Hz, 1H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.5 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.6 (s), 139.6 (s), 137.1 (s), 135.6 (s), 133.6 (s), 129.8 (s), 127.2 (s), 124.8 (s), 120.5 (q, J = 336.9 Hz), 120.2 (s), 111.3 (s), 100.9 (s), 70.5 (q, J = 3.0 Hz), 21.5 (s)

[0060] Substrate Formula 14

[0061]

[0062] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(4-chloro-2-ethynylphenyl)-4-methylbenzenesulfonamide (CAS: 1616975-00-8), 2.8 mmol of trifluoromethyl copper selenolate bispyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added. The reaction was stirred at room temperature under air for 10-30 min, and the progress of the reaction was followed by TLC. After the completion of the reaction, the reaction mixture was diluted with 20 mL of deionized water and the mixture was extracted with 3 x 15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, N-(4-chloro-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide, was isolated by column chromatography on silica gel using petroleum ether and ethyl acetate (20:1, v / v) as eluents (35% isolated yield) and characterized by the following data: 1 H NMR (400 MHz, CDC13) δ 7.64 (d, J = 8.3 Hz, 2H), 7.62 - 7.58 (m, 1H), 7.33 - 7.27 (m, 2H), 7.23 (d, J = 8.1 Hz, 2H), 7.07 (s, 1H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.2 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.5 (s), 137.0 (s), 135.6 (s), 132.2 (s), 131.1 (s), 130.0 (s), 129.8 (s), 127.2 (s), 122.0 (s), 120.5 (q, J = 336.8 Hz), 114.9 (s), 100.6 (s), 70.7 (q, J = 3.1 Hz), 21.5 (s)

[0063] Substrate Formula 15

[0064]

[0065] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 2.0 mmol of N-(4-bromo-2-ethynylphenyl)-4-methylbenzenesulfonamide (CAS: 1616975-01-9), 2.8 mmol of trifluoromethyl copper selenolate bispyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride, and finally 20 mL of anhydrous acetonitrile solvent were added. The reaction was stirred at room temperature in air for 10-30 min, and the progress of the reaction was followed by TLC. After the completion of the reaction, the reaction mixture was diluted with 20 mL of deionized water and the mixture was extracted with 3 x 15 mL of ethyl acetate. The organic phase was washed with 10.0 mL of saturated sodium chloride solution, dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, N-(4-bromo-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide, was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (20:1, v / v) as eluents (40% isolated yield) and characterized by the following data: 1 H NMR (400 MHz, CDC13) δ 7.67 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 9.5 Hz, 1H), 7.47 - 7.40 (m, 2H), 7.27 - 7.19 (m, 3H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.3 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.5 (s), 137.5 (s), 135.6 (s), 135.0 (s), 133.9 (s), 129.8 (s), 127.2 (s), 122.2 (s), 120.5 (q, J = 338.3 Hz), 117.3 (s), 115.2 (s), 100.4 (s), 71.0 (q, J = 3.1 Hz), 21.5 (s)

[0066] Substrate Formula 16

[0067]

[0068] In a 10 mL reaction tube equipped with a magnetic stir bar of polytetrafluoroethylene, 2.0 mmol of N-(5-bromo-2-ethynylphenyl)-4-methylbenzenesulfonamide (CAS: 2623279-75-2), 2.8 mmol of trifluoromethyl copper selenolate bispyridine complex [(bpy)Cu(SeCF3)]2, 6.0 mmol of Dess-Martin periodinane, 4.0 mmol of potassium fluoride were added, finally 20 mL of anhydrous acetonitrile solvent was added, stirred at room temperature for 10-30 min in air, the reaction was tracked by TLC. After the reaction was completed, it was diluted with 20 mL of deionized water, and the mixed solution was extracted with 3x15 mL of ethyl acetate, the organic phase was washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgSO4, filtered and the solvent was removed by rotary evaporation, and N-(5-bromo-2-((trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide was obtained by silica gel column chromatography separation with petroleum ether and ethyl acetate (20:1, v / v) as eluent (isolation yield 39%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 7.83 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.1 Hz, 2H), 7.20 - 7.16 (m, 3H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -35.4 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 144.6 (s), 139.5 (s), 135.5 (s), 133.7 (s), 129.8 (s), 127.7 (s), 127.2 (s), 125.2 (s), 123.2 (s), 120.5 (q, J = 336.9 Hz), 111.8 (s), 100.9 (s), 70.7 (q, J = 3.1 Hz), 21.5 (s).

[0069] Example 1

[0070]

[0071] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(2-((trifluoromethyl)seleno)ethynyl)phenyl)benzenesulfonamide (CAS: 2761259-47-4), 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, finally 1.5 mL of toluene solvent was added, the reaction was stirred at 120 °C in an oil bath for 3 h after cooling to room temperature in a glove box, 0.45 mmol of NBS was added, the mixture was continued to stir at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, then washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgS04, filtered and the solvent was removed by rotary evaporation, and eluted with petroleum ether and ethyl acetate (10:1, v / v) to separate by silica gel column chromatography to obtain 2-bromo-1-tosyl-3- trifluoromethylseleno-1H-indole (separation yield 91%), its characterization data are: 1 H NMR (400 MHz, CDC13) δ 8.32 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 7.8 Hz, 1H), 7.37 (dt, J = 22.3, 7.4 Hz, 2H), 7.24 (d, J = 8.5 Hz, 2H), 2.36 (s, 4H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 146.0 (s), 137.2 (s), 134.9 (s), 131.2 (s), 130.0 (s), 127.3 (s), 125.9 (s), 124.8 (s), 121.9 (s), 121.8 (q, J = 337.3 Hz), 120.5 (s), 115.2 (s), 107.5 (s), 21.6 (s).

[0072] Example 2

[0073]

[0074] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(4-methyl-2-(trifluoromethyl)seleno)ethynyl)phenyl benzene sulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, and finally 1.5 mL of toluene solvent was added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, and then washed with 10.0 mL of saturated sodium chloride solution. The organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 2-bromo-5-methyl-1-toluenesulfonyl-3- trifluoromethylseleno-1H-indole was obtained by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolation yield 88%), and its characterization data were as follows: 1 H NMR (400 MHz, CDC13) δ 8.18 (d, J = 8.6 Hz, 1H), 7.78 (d, J = 8.4 Hz, 2H), 7.39 (s, 1H), 7.27 - 7.18 (m, 3H), 2.46 (s, 3H), 2.36 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.79 (s, 3F). 13 CNMR (101 MHz, CDC13) δ 145.8 (s), 135.4 (s), 134.9 (s), 134.7 (s), 131.3 (s), 129.9 (s), 127.3 (s), 127.2 (s), 121.8 (s), 120.2 (s), 122.0 (q, J = 337.3 Hz), 114.9 (s), 107.3 (d, J = 1.7 Hz), 21.6 (s), 21.2 (s).

[0075] Example 3

[0076]

[0077] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(5-methyl-2-(trifluoromethyl)seleno)ethynyl)phenyl benzene sulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 2-bromo-6-methyl-1-toluenesulfonyl-3- trifluoromethylseleno-1H-indole was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 95%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.19 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 8.1 Hz, 2H), 7.40 (s, 1H), 7.25 - 7.19 (m, 3H), 2.47 (s, 3H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 CNMR (101 MHz, CDC13) δ 145.8 (s), 135.4 (s), 134.9 (s), 134.7 (s), 131.3 (s), 129.9 (s), 127.3 (s), 127.2 (s), 121.8 (s), 120.3 (q, J = 337.3 Hz), 120.2 (s), 114.9 (s), 107.3 (d, J = 1.8 Hz), 21.6 (s), 21.2 (s).

[0078] Example 4

[0079]

[0080] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of methyl 2-(4-(4-methylphenyl)sulfonamido)-3-((trifluoromethyl)seleno)ethynyl)phenyl)acetate, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Column chromatography on silica gel using petroleum ether and ethyl acetate (10:1, v / v) as eluent gave methyl 2-(2-bromo-1-methylsulfanyl-3-(trifluoromethylseleno)-1H-indol-5-yl)acetate (isolated yield 33%), whose characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.27 (d, J = 8.7 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.53 (s, 1H), 7.33 (dd, J = 8.7, 1.9 Hz, 1H), 7.26 (d, J = 8.1 Hz, 2H), 3.75 (s, 2H), 3.71 (s, 3H), 2.38 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 171.9 (s), 146.0 (s), 136.3 (s), 134.9 (s), 131.4 (s), 130.7 (s), 130.0 (s), 127.3 (s), 127.2 (s), 122.2 (s), 122.0 (q, J = 337.3 Hz), 121.0 (s), 115.3 (s), 107.1 (s), 52.1 (s), 40.8 (s), 21.7 (s).

[0081] Example 5

[0082]

[0083] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4- ethyl-2-(trifluoromethyl) seleno) ethynyl) phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 2-bromo-5-ethyl-1-tosyl-3- trifluoromethylseleno-1H-indole, was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 77%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.21 (d, J = 8.6 Hz, 1H), 7.80 (d, J = 8.5 Hz, 2H), 7.42 (s, 1H), 7.24 (d, J = 7.1 Hz, 3H), 2.76 (q, J = 7.6 Hz, 2H), 2.37 (s, 3H), 1.28 (t, J = 7.6 Hz, 3H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 145.8 (s), 141.1 (s), 135.5 (s), 135.0 (s), 131.3 (s), 129.9 (s), 127.2 (s), 126.2 (s), 122.0 (q, J = 338.3 Hz), 121.6 (s), 119.0 (s), 115.0 (s), 107.4 (d, J = 1.9 Hz), 28.6 (s), 21.6 (s), 15.8 (s).

[0084] Example 6

[0085]

[0086] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4-tert-butyl)-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the resulting organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Column chromatography was performed on silica gel using petroleum ether and ethyl acetate (10:1, v / v) as eluent to obtain 2-bromo-5-tert-butyl-1-toluenesulfonyl-3-trifluoromethylseleno-1H-indole (separation yield 74%), whose characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.22 (d, J = 9.5 Hz, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.60 (d, J = 2.0 Hz, 1H), 7.46 (dd, J = 9.0, 2.0 Hz, 1H), 7.26 (t, J = 3.9 Hz, 3H), 2.38 (s, 3H), 1.38 (s, 9H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 148.0 (s), 145.8 (s), 135.2 (s), 135.1 (s), 130.8 (s), 130.0 (s), 127.3 (s), 123.9 (s), 122.1 (q, J = 337.3 Hz), 121.3 (s), 116.7 (s), 114.7 (s), 107.6 (s), 34.7 (s), 31.5 (s), 21.7 (s).

[0087] Example 7

[0088]

[0089] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(3-(trifluoromethyl)seleno)-[1,1'-biphenyl]-4-yl)benzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system. After cooling to room temperature, 0.45 mmol of NBS was added in a glove box. The mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate and washed with 10.0 mL of saturated sodium chloride solution. The organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 2-bromo-5-phenyl-1-tosyl-3- trifluoromethylseleno-1H-indole, was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (96% isolated yield). The characterization data are as follows: 1 HNMR (400 MHz, CDC13) δ 8.37 (d, J = 8.8 Hz, 1H), 7.87 - 7.79 (m, 3H), 7.63 (d, J = 8.1 Hz, 2H), 7.46 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.3 Hz, 1H), 7.26 (d, J = 8.1 Hz, 2H), 2.36 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 146.1 (s), 140.5 (s), 138.2 (s), 136.6 (s), 134.9 (s), 131.7 (s), 130.1 (s), 128.9 (s), 127.5 (s), 127.4 (s), 127.3 (s), 125.3 (s), 122.4 (s), 122.1 (q, J = 336.2 Hz), 118.7 (s), 115.5 (s), 107.7 (d, J = 1.9 Hz), 21.7 (s).

[0090] Example 8

[0091]

[0092] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4-methoxy-2-(trifluoromethyl) seleno) ethynyl) phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, finally 1.5 mL of toluene solvent was added, the reaction was stirred at 120 °C in an oil bath for 3 h, then cooled to room temperature, 0.45 mmol of NBS was added in a glove box, the mixture was continued to stir at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, then washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgS04, filtered and the solvent was removed by rotary evaporation, and then separated by silica gel column chromatography with petroleum ether and ethyl acetate (10:1, v / v) as eluent to obtain 2-bromo-5-methoxy-1-tosyl-3- trifluoromethylseleno-1H-indole (separation yield 78%), and its characterization data were as follows: 1 H NMR (400 MHz, CDC13) δ 8.20 (d, J = 9.2 Hz, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.06 - 6.96 (m, 2H), 3.86 (s, 3H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 157.4 (s), 145.9 (s), 134.8 (s), 132.4 (s), 131.7 (s), 129.9 (s), 127.2 (s), 122.1 (s), 122.0 (q, J = 336.3 Hz), 116.4 (s), 115.0 (s), 107.5 (d, J = 1.9 Hz), 102.4 (s), 55.7 (s), 21.6 (s).

[0093] Example 9

[0094]

[0095] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-(4- methylphenyl)sulfonamido)-3-((trifluoromethyl)seleno)ethynyl)benzoic acid methyl ester, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, and finally 1.5 mL of toluene solvent was added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, and then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, and then washed with 10.0 mL of saturated sodium chloride solution. The organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 2-bromo-1- methylsulfanyl-3-((trifluoromethyl)seleno)indole-5-carboxylic acid methyl ester, was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolation yield 43%), and its characterization data were as follows: 1 H NMR (400 MHz, DMSO-d6) δ 13.21 (s, 1H), 8.00 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.3 Hz, 1H), 3.86 (s, 2H). 19 F NMR (376 MHz, DMSO-d6) δ -36.7 (s, 3F). 13 CNMR (101 MHz, DMSO-d6) δ 167.0 (s), 136.3 (s), 134.2 (s), 126.3 (s), 124.3 (s), 123.0 (q, J = 336.9 Hz), 122.4 (s), 119.1 (s), 113.6 (s), 95.1 (s), 52.5 (s).

[0096] Example 10

[0097]

[0098] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(4-trifluoromethyl)-2-(trifluoromethyl)seleno)ethynyl)phenyl)benzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Column chromatography was performed on silica gel using petroleum ether and ethyl acetate (10:1, v / v) as eluent to obtain 2-bromo-1-tosyl-5-trifluoromethyl-3-trifluoromethylseleno-1H-indole (33% isolated yield), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.46 (d, J = 8.9 Hz, 1H), 7.91 (s, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.9 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 2.40 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F), -61.5 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 146.5 (s), 138.6 (s), 134.6 (s), 131.1 (s), 130.2 (s), 127.4 (s), 125.5 (q, J = 313.9 Hz), 124.1 (q, J = 272.1 Hz), 122.5 (q, J = 3.5 Hz), 121.9 (q, J = 336.0 Hz), 118.0 (q, J = 4.3 Hz), 115.7 (s), 107.2 (s), 21.7 (s).

[0099] Example 11

[0100]

[0101] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(5- fluoro-2-(trifluoromethyl) seleno) ethynyl) phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system. After cooling to room temperature, 0.45 mmol of NBS was added in a glove box. The mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product, 2-bromo-6-fluoro-1-tosyl-3- trifluoromethylseleno-1 H-indole, was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 73%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.09 (dd, J = 10.2, 2.3 Hz, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.57 (dd, J = 8.7, 5.4 Hz, 1H), 7.29 (d, J = 8.3 Hz, 2H), 7.12 (td, J = 8.8, 2.3 Hz, 1H), 2.39 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F), -114.1 (td, J = 9.6, 5.4 Hz, 1F). 13 C NMR (101 MHz, CDC13) δ 162.6 (s), 160.2 (s), 146.3 (s), 137.0 (d, J = 12.8 Hz), 134.7 (s), 130.1 (s), 127.5 (s), 127.4 (s), 121.8 (q, J = 338.3 Hz), 121.5 (d, J = 9.8 Hz), 113.3 (d, J = 24.4 Hz), 107.0 (s), 102.8 (d, J = 29.9 Hz), 21.7 (s).

[0102] Example 12

[0103]

[0104] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4-chloro-2-(trifluoromethyl) seleno) ethynyl) phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, finally 1.5 mL of toluene solvent was added, the reaction was stirred at 120 °C oil bath condition in a closed system for 3 h, then cooled to room temperature, 0.45 mmol of NBS was added in the glove box, the mixture was continued to stir at room temperature for 2 hours. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, then washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgSO4, filtered and the solvent was removed by rotary evaporation, and eluted with petroleum ether and ethyl acetate (10:1, v / v) to separate by silica gel column chromatography to obtain 2-bromo-5-chloro-1-tosyl-3- trifluoromethylseleno-1H-indole (isolation yield 53%), its characterization data are: 1 HNMR (400 MHz, CDCI3) δ 8.26 (d, J = 9.0 Hz, 1 H), 7.79 (d, J = 8.5 Hz, 2 H), 7.60 (d, J = 2.1 Hz, 1 H), 7.36 (dd, J = 9.0, 2.2 Hz, 1 H), 7.27 (d, J = 8.8 Hz, 3 H), 2.39 (s, 3 H). 19 F NMR (376 MHz, CDCI3) δ -34.6 (s, 3 F). 13 C NMR (101 MHz, CDCI3) δ 146.3 (s), 135.5 (s), 134.6 (s), 132.5 (s), 130.9 (s), 130.1 (s), 127.3 (s), 126.1 (s), 123.4 (s), 121.9 (q, J = 337.3 Hz), 120.1 (s), 116.4 (s), 106.6 (s), 21.7 (s).

[0105] Example 13

[0106]

[0107] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(5-bromo-2-((trifluoromethyl)seleno)methyl)phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NBS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 2,6-dibromo-1 -methylsulfanyl-3-(trifluoromethylseleno)-1 H-indole was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolation yield 44%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.53 (s, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.49 (s, 2H), 7.30 (d, J = 8.2 Hz, 2H), 2.40 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.7 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 146.4 (s), 137.5 (s), 134.6 (s), 130.1 (s), 130.1 (s), 128.2 (s), 127.4 (s), 122.4 (s), 121.97 (q, J = 336.2 Hz), 121.6 (s), 119.8 (s), 118.1 (s), 107.1 (d, J = 2.0 Hz), 21.7 (s).

[0108] Example 14

[0109]

[0110] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(2-((trifluoromethyl)seleno)ethynyl)phenyl)benzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 2-iodo-1-methylsulfonyl-3- trifluoromethylseleno-1H-indole was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 90%), and its characterization data were: 1 HNMR (400 MHz, CDC13) δ 8.34 (dd, J = 7.0, 2.6 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.67 - 7.59 (m, 1H), 7.35 - 7.27 (m, 2H), 7.23 (d, J = 8.2 Hz, 2H), 2.35 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 145.8 (s), 138.7 (s), 134.9 (s), 132.3 (s), 129.9 (s), 127.4 (s), 125.7 (s), 124.6 (s), 122.3 (q, J = 337.3 Hz) 121.1 (s), 116.40 (s), 115.6 (s), 95.8 (s), 21.6 (s).

[0111] Example 15

[0112]

[0113] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(4-methyl-2-(trifluoromethyl)seleno)ethynyl)phenyl benzene sulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, finally 1.5 mL of toluene solvent was added, the mixture was stirred at 120 °C in an oil bath for 3 h, then cooled to room temperature, 0.45 mmol of NIS was added in a glove box, the mixture was continued to stir at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, then washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgS04, filtered and the solvent was removed by rotary evaporation, and 2-iodo-5-methyl-1-tosyl-3- trifluoromethylseleno-1H-indole (isolation yield 39%) was obtained by silica gel column chromatography with petroleum ether and ethyl acetate (10:1, v / v) as eluent, and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.20 (d, J = 8.6 Hz, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.41 (s, 1H), 7.23 (d, J = 8.1 Hz, 2H), 7.14 (d, J = 8.7 Hz, 1H), 2.46 (s, 3H), 2.36 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 145.7 (s), 137.0 (s), 134.9 (s), 134.5 (s), 132.4 (s), 129.9 (s), 127.3 (s), 127.1 (s), 122.4 (q, J = 337.3 Hz), 120.7 (s), 116.1 (s), 115.3 (s), 95.6 (s), 21.6 (s), 21.2 (s).

[0114] Example 16

[0115]

[0116] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(5-methyl-2-(trifluoromethyl) selenoethynyl) phenyl) benzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 2-iodo-6-methyl-1-tosyl-3- trifluoromethylseleno-1H-indole was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 79%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.15 (s, 1H), 7.80 (d, J = 8.3 Hz, 2H), 7.50 (d, J = 8.1 Hz, 1H), 7.24 (d, J = 8.2 Hz, 2H), 7.13 (d, J = 8.1 Hz, 1H), 2.52 (s, 3H), 2.36 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 145.7 (s), 139.1 (s), 136.1 (s), 135.1 (s), 130.2 (s), 129.9 (s), 127.3 (s), 126.1 (s), 122.4 (q, J = 337.3 Hz), 120.6 (s), 116.3 (d, J = 1.7 Hz), 115.6 (s), 94.5 (s), 22.0 (s), 21.6 (s).

[0117] Example 17

[0118]

[0119] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of methyl 2-(4-(4-methylphenyl)sulfonamido)-3-((trifluoromethyl)seleno)ethynyl)phenyl)acetate, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, and finally 1.5 mL of toluene solvent was added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, and then washed with 10.0 mL of saturated sodium chloride solution. The organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Column chromatography was performed on silica gel with petroleum ether and ethyl acetate (10:1, v / v) as eluent to obtain methyl 2-(2-iodo-1- toluenesulfonyl-3-(trifluoromethylseleno)-1H-indol-5-yl)acetate (55% separation yield), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.28 (d, J = 8.7 Hz, 1H), 7.82 (d, J = 8.3 Hz, 2H), 7.55 (s, 1H), 7.30 - 7.23 (m, 3H), 3.75 (s, 2H), 3.70 (s, 3H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 171.9 (s), 145.9 (s), 137.8 (s), 134.9 (s), 132.5 (s), 130.6 (s), 130.0 (s), 127.4 (s), 127.0 (s), 122.4 (q, J = 336.5 Hz), 121.5 (s), 115.9 (d, J = 1.7 Hz), 115.6 (s), 96.1 (s), 52.1 (s), 40.7 (s), 21.7 (s).

[0120] Example 18

[0121]

[0122] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4- ethyl-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. Column chromatography on silica gel with petroleum ether and ethyl acetate (10:1, v / v) as eluent gave 5-ethyl-2-iodo-1- toluenesulfonyl-3-trifluoromethylseleno-1H-indole (68% isolated yield), which had the following characterization data: 1 H NMR (400 MHz, CDC13) δ 8.22 (d, J = 8.7 Hz, 1H), 7.80 (d, J = 8.1 Hz, 2H), 7.43 (s, 1H), 7.22 (d, J = 8.2 Hz, 2H), 7.17 (d, J = 8.7 Hz, 1H), 2.75 (q, J = 7.6 Hz, 2H), 2.34 (s, 3H), 1.27 (t, J = 7.6 Hz, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 145.7 (s), 141.0 (s), 137.1 (s), 135.0 (s), 132.4 (s), 129.9 (s), 127.4 (s), 126.1 (s), 120.8 (q, J = 337.3 Hz), 119.5 (s), 116.2 (d, J = 1.7 Hz), 115.4 (s), 95.5 (s), 28.6 (s), 21.6 (s), 15.8 (s).

[0123] Example 19

[0124]

[0125] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of 4-methyl-N-(3-(trifluoromethyl)seleno)-[1,1'-biphenyl]-4-yl)benzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system. After cooling to room temperature, 0.45 mmol of NIS was added in a glove box and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the resulting organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 2-iodo-5-phenyl-1-tosyl-3- trifluoromethylseleno-1H-indole was isolated by column chromatography on silica gel using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolation yield 52%) and its characterization data were: 1 HNMR (400 MHz, CDC13) δ 8.39 (d, J = 8.8 Hz, 1H), 7.88 - 7.77 (m, 3H), 7.63 (d, J = 7.7 Hz, 2H), 7.57 (d, J = 8.9 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.37 (t, J = 7.2 Hz, 1H), 7.26 (d, J = 8.1 Hz, 2H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.5 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 145.9 (s), 140.4 (s), 138.0 (s), 134.9 (s), 132.8 (s), 130.0 (s), 128.9 (s), 127.5 (s), 127.4 (s), 127.4 (s), 125.1 (s), 122.4 (q, J = 337.3 Hz), 119.2 (s), 116.5 (s), 115.9 (s), 96.3 (s), 21.7 (s).

[0126] Example 20

[0127]

[0128] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4- fluoro-2-(trifluoromethyl) seleno) ethynyl) phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene), and finally 1.5 mL of toluene solvent were added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, washed with 10.0 mL of saturated sodium chloride solution, and the organic phase was dried over anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 5-fluoro-2-iodo-1- toluenesulfonyl-3-trifluoromethylseleno-1H-indole was isolated by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 79%), and its characterization data were: 1 H NMR (400 MHz, CDC13) δ 8.30 (dd, J = 9.2, 4.3 Hz, 1H), 7.80 (d, J = 8.4 Hz, 2H), 7.36 - 7.22 (m, 3H), 7.06 (td, J = 9.1, 2.7 Hz, 1H), 2.37 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F), -117.34 - -117.50 (m, 1F). 13 C NMR (101 MHz, CDC13) δ 161.4 (s), 159.0 (s), 146.1 (s), 135.0 (s), 134.6 (s), 133.5 (d, J = 10.2 Hz), 130.0 (s), 127.4 (s), 122.3 (q, J = 336.4 Hz), 117.0 (d, J = 9.0 Hz), 113.8 (d, J = 25.4 Hz), 106.6 (d, J = 25.1 Hz), 97.7 (s), 21.7 (s).

[0129] Example 21

[0130]

[0131] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(5-chloro-2-(trifluoromethyl)seleno)ethynyl)phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, and finally 1.5 mL of toluene solvent was added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, and then washed with 10.0 mL of saturated sodium chloride solution. The organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 6-chloro-2-iodo-1-tosyl-3- trifluoromethylseleno-1 H-indole was obtained by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolated yield 63%), and its characterization data were as follows: 1 HNMR (400 MHz, CDC13) δ 8.41 (d, J = 1.8 Hz, 1H), 7.85 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.5 Hz, 1H), 7.36 - 7.27 (m, 3H), 2.41 (s, 3H). 19 F NMR (376 MHz, CDC13) δ -34.6 (s, 3F). 13 C NMR (101 MHz, CDC13) δ 146.2 (s), 138.6 (s), 134.7 (s), 132.0 (s), 130.8 (s), 130.1 (s), 127.5 (s), 125.4 (s), 124.8 (s), 122.3 (q, J = 337.3 Hz), 121.8 (s), 115.6 (s), 96.2 (s), 21.7 (s).

[0132] Example 22

[0133]

[0134] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(4-bromo-2-(trifluoromethyl) seleno) ethynyl) phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, finally 1.5 mL of toluene solvent was added, the reaction was stirred at 120 °C in an oil bath for 3 h, then cooled to room temperature, 0.45 mmol of NIS was added in a glove box, the mixture was continued to stir at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, then washed with 10.0 mL of saturated sodium chloride solution, the obtained organic phase was dried with anhydrous MgS04, filtered and the solvent was removed by rotary evaporation, and eluted with petroleum ether and ethyl acetate (10:1, v / v) to separate 5-bromo-2-iodo-1-tosyl-3- trifluoromethylseleno-1H-indole (51% separation yield), and its characterization data were: 1 HNMR (400 MHz, DMSO-d6) δ 8.22 (d, J = 9.0 Hz, 1H), 7.84 (d, J = 8.3 Hz, 2H), 7.69 (d, J = 2.1 Hz, 1H), 7.55 (dd, J = 9.0, 2.1 Hz, 1H), 7.45 (d, J = 8.2 Hz, 2H), 2.35 (s, 3H). 19 F NMR (376 MHz, DMSO-d6) δ -35.4 (s, 3F). 13 C NMR (101 MHz, DMSO-d6) δ 147.0 (s), 137.0 (s), 134.3 (s), 134.1 (s), 130.9 (s), 128.7 (s), 127.5, 123.3 (q, J = 338.3 Hz), 123.2 (s), 118.0 (s), 117.6 (s), 115.6 (d, J = 2.1 Hz), 103.6 (s), 21.5 (s).

[0135] Example 23

[0136]

[0137] In a 10 mL reaction tube equipped with a Teflon magnetic stir bar, 0.3 mmol of N-(5-bromo-2-((trifluoromethyl)seleno)methyl)phenyl)-4-methylbenzenesulfonamide, 0.6 mmol of anhydrous zinc chloride, 0.36 mmol of diethylzinc (1 M solution in toluene) were added, and finally 1.5 mL of toluene solvent was added. The reaction was stirred at 120 °C in an oil bath for 3 h in a closed system, then cooled to room temperature. In the glove box, 0.45 mmol of NIS was added, and the mixture was stirred at room temperature for 2 h. After the reaction was completed, the mixture was diluted with 5 mL of ethyl acetate, and then washed with 10.0 mL of saturated sodium chloride solution. The organic phase was dried with anhydrous MgS04, filtered, and the solvent was removed by rotary evaporation. The product 6-bromo-2-iodo-1 -methylsulfanyl-3- (trifluoromethylseleno)-1 H-indole was obtained by silica gel column chromatography using petroleum ether and ethyl acetate (10:1, v / v) as eluent (isolation yield 57%), and its characterization data were: 1 H NMR (400 MHz, DMSO-d6) δ 8.40 (d, J = 1.6 Hz, 1H), 7.85 (d, J = 8.5 Hz, 2H), 7.60 - 7.52 (m, 2H), 7.47 (d, J = 8.2 Hz, 2H), 2.36 (s, 3H). 19 F NMR (376 MHz, DMSO-d6) δ -35.4 (s, 3F). 13 C NMR (101 MHz, DMSO-d6) δ 147.0 (s), 138.5 (s), 134.3 (s), 131.5 (s), 130.9 (s), 128.4 (s), 127.7 (s), 123.3 (q, J = 337.3 Hz), 122.8 (s), 119.0 (s), 117.9 (s), 116.4 (s), 102.5 (s), 21.6 (s).

[0138] Application Example: Pine Wood Nematode Test

[0139] The pine wood nematode is separated from the culture medium, and the concentration is 200-300 pieces per ml. The products obtained in Examples 1-23 are respectively dissolved in 20 ml of ethyl acetate, 80 ml of distilled water, and 100 μl of triton to form the test solution, which is further diluted to 5-6 different concentration gradients of the test drug solution for standby. In each well of the 96-well plate, 100 μl of the pine wood nematode suspension is added, and then 10 μl of the test drug solution of different concentrations is respectively added, with 3 repeats in each group. The control group is added with 10 μl of the blank solution. The 96-well plate is sealed with a sealing film, labeled, and placed in a 30°C constant temperature box for culture. After 24 hours, the survival and death of the pine wood nematode are recorded under a stereomicroscope (the judgment method of the death and survival of the nematode: the nematode with a wave shape, a curled shape, an "S" shape, a spiral shape, and in motion is regarded as survival. The nematode with a needle shape, a "J" shape, or a "C" shape, or without birefringence of the worm body wall, and without motion is regarded as death). The results show that the nematodes in the control group can grow normally, and the death rate of the nematodes in the drug administration group is more than 65% when the sample concentration is 10 mg / L. Among them, the death rates of the nematodes of 2-(2-iodo-1-methyl toluene sulfonyl-3-(trifluoromethyl seleno)-1H-indole-5-yl) acetic acid methyl ester, 2,6-dibromo-1-methyl toluene sulfonyl-3-(trifluoromethyl seleno)-1H-indole, and 6-bromo-2-iodo-1-methyl toluene sulfonyl-3-(trifluoromethyl seleno)-1H-indole are 65%, 70%, and 75% respectively when the concentration is 10 mg / L.

[0140] The above only describes the preferred embodiments of the present application, and any equivalent changes and modifications made within the scope of the patent application of the present application shall be included in the scope of the present application.

Claims

1. A method for the synthesis of 2-substituted-3-trifluoromethylselenoindole compounds, characterized by: The 2-trifluoromethylselenoacetylene aniline derivative is any one of the following formula 1 to formula 16: Wherein, Ts = p-tolylsulfonyl; ； The zinc salt is one of ZnCl2, ZnI2 and ZnBr2; The electrophilic reagent is one of N-bromosuccinimide and N-iodosuccinimide; When the electrophilic reagent is N-bromosuccinimide, the obtained 2-bromo-3-trifluoromethylselenoindole compound is any one of the following formula 1 to formula 16: Wherein, Ts = p-tolylsulfonyl; ； When the electrophilic reagent is N-bromosuccinimide, the obtained 2-bromo-3-trifluoromethylselenoindole compound is any one of the following formula 1 to formula 16: Wherein, Ts = p-tolylsulfonyl. ； Specifically, the 2-trifluoromethylselenoacetylene aniline derivative, diethyl zinc and zinc salt are mixed in a solvent, and after magnetic stirring at 110-150 DEG C for 2-6 h, an electrophilic reagent is added, and the reaction is carried out at room temperature for 1-4 h, then the reaction mixture is diluted with ethyl acetate, washed with saturated sodium bicarbonate solution, and the obtained organic phase is dried over anhydrous MgSO4, filtered and rotary evaporated to remove the solvent, and then purified by silica gel column to obtain the 2-substituted-3-trifluoromethylselenoindole compound.

2. The method of synthesis of claim 1, wherein: The molar ratio of the 2-trifluoromethylselenoacetylene aniline derivative, diethyl zinc, zinc salt and electrophilic reagent is (0.2-1):(1-10):(0.6-5):(0.6-5).

3. The method of synthesis of claim 2, wherein: ​

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