An electrophilic trifluoromethylselenation reagent, its preparation method and applications

Abstract

The present invention discloses an electrophilic trifluoromethylselenation reagent, its preparation method and application. The structure of the electrophilic trifluoromethylselenation reagent is shown in the following formula: #imgabs0# The present invention also specifically discloses the preparation method of the electrophilic trifluoromethylselenation reagent and its application in the preparation of trifluoromethylselenide-containing compounds. The electrophilic trifluoromethylselenation reagent prepared by the present invention can activate alkynes for electrophilic trifluoromethylselenation reaction, and then prepare trifluoromethylselenide-substituted isoxazole compounds, realizing the introduction of the SeCF3 group into the compound, and finally constructing and synthesizing different types of trifluoromethylselenide compounds with lipophilicity. The electrophilic trifluoromethylselenation reagent prepared by the present invention has the advantages of strong electrophilicity, high reaction efficiency, wide substrate scope, etc.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation and application of trifluoromethylselenation reagents, and particularly relates to an electrophilic trifluoromethylselenation reagent, a preparation method thereof and an application thereof. Background Art

[0002] Fluorine is a special element. Introducing fluorine-containing groups into organic molecules can improve their physical and chemical properties, and it has become a popular field in drug research and development. Selenium is an essential trace element for the human body, an important component of antioxidant enzymes, directly participating in the body's metabolism, promoting growth and development, and playing a crucial role in human health. Therefore, the SeCF3 group formed by the combination of selenium and fluorine has received extensive attention. Research shows that the SeCF3 group has good lipophilicity (π R = 1.29), which is beneficial to improving the penetration of organic molecules and the utilization rate of drugs. Therefore, by introducing the SeCF3 group into compounds to construct and synthesize different types of trifluoromethylseleno compounds, it has broad application prospects in the fields of new drugs, pesticides, organic synthesis, etc.

[0003] Currently, there are mainly two methods for constructing trifluoromethylseleno compounds: the indirect method and the direct method. The indirect synthesis method requires the prior preparation of an organic selenium compound precursor and then a trifluoromethylselenation reaction, resulting in cumbersome steps and limited applications. The direct method can directly introduce a trifluoromethylseleno group into a molecule, and it is a trifluoromethylselenation method that has developed more rapidly in recent years. The direct trifluoromethylselenation method mainly includes three types: nucleophilic trifluoromethylselenation, radical trifluoromethylselenation, and electrophilic trifluoromethylselenation.

[0004] In the method of nucleophilic trifluoromethylselenylation, two trifluoromethylselenylation reagents, namely (Me4N)SeCF3 and [(bpy)Cu(SeCF3)]2, are commonly used. Zhang Chengpan et al. successfully achieved the trifluoromethylselenylation reaction of aryl diazonium tetrafluoroborates and the trifluoromethylselenylation reaction of alcohol dehydroxylation using (Me4N)SeCF3. The [(bpy)Cu(SeCF3)]2 developed by the research group of Weng Zhiqiang achieved the trifluoromethylselenylation reactions of aryl halides, alkyl halides, terminal alkynes, etc. In the method of radical trifluoromethylselenylation, photocatalysis or an oxidant is used to react with reagents such as TsSeCF3 and (Me4N)SeCF3 to generate trifluoromethylselenium radicals for trifluoromethylselenylation reactions. In the method of electrophilic trifluoromethylselenylation, the electrophilic trifluoromethylselenylation reagents are very limited. Commonly, CF3SeCl and CF3SeSeCF3 are used as electrophilic SeCF3 sources. Due to their properties such as low boiling point and easy volatility, their applications and developments are restricted. In 2017, the Billard research group developed a new type of electrophilic trifluoromethylselenylation reagent, TsSeCF3. This electrophilic trifluoromethylselenylation reagent successfully achieved the trifluoromethylselenylation reactions of terminal alkynes, boric acid, and heteroaromatic hydrocarbons. However, the yields of the electrophilic reactions carried out by this electrophilic trifluoromethylselenylation reagent are generally average, and the electrophilic ability is relatively weak.

[0005] Therefore, electrophilic trifluoromethylselenylation reagents need to be further explored. Developing new trifluoromethylselenylation reagents that are easily accessible, have high electrophilic activity, and a wide range of applications is an urgent problem to be solved. Summary of the Invention

[0006] In view of the many problems in the prior art, such as low boiling point, high toxicity, and limited applications of electrophilic trifluoromethylselenylation reagents, the present invention provides an electrophilic trifluoromethylselenylation reagent and a preparation method thereof. The electrophilic trifluoromethylselenylation reagent prepared by the present invention can activate alkynes for electrophilic trifluoromethylselenylation reactions, and then prepare trifluoromethylselenium-substituted isoxazole compounds, realizing the introduction of the SeCF3 group into the compound, and finally constructing and synthesizing different types of trifluoromethylselenium compounds with lipophilicity. The electrophilic trifluoromethylselenylation reagent prepared by the present invention has the advantages of strong electrophilicity, high reaction efficiency, and a wide range of substrate applicability.

[0007] The technical solution adopted by the present invention is as follows: An electrophilic trifluoromethylselenylation reagent has the following structural formula:

[0008]

[0009] The present invention provides a preparation method of the electrophilic trifluoromethylselenylation reagent. The specific steps are as follows: In an organic solvent, compound 1a and trifluoromethylselenyl chloride are reacted at -100°C to 50°C to obtain compound 1. The reaction equation is as follows:

[0010]

[0011] In the preparation method of the electrophilic trifluoromethylselenation reagent, the organic solvent is a conventional organic solvent for such reactions in the art, as long as it does not react with the reactants or products. In the present invention, one or more of halogenated hydrocarbon solvents, ether solvents or nitrile solvents are selected, and halogenated hydrocarbon solvents are particularly preferred, and dichloromethane is further preferred.

[0012] In the preparation method of the electrophilic trifluoromethylselenation reagent, the volume-mass ratio of the organic solvent to Compound 1a is 1 mL / g to 100 mL / g, preferably 1 mL / g to 20 mL / g.

[0013] In the preparation method of the electrophilic trifluoromethylselenation reagent, the molar ratio of Compound 1a to chlorotrifluoromethyl selenide is 1:1 to 5:1, preferably 1:1 to 2:1.

[0014] In the preparation method of the electrophilic trifluoromethylselenation reagent, the reaction temperature is -100 °C to 0 °C.

[0015] In the preparation method of the electrophilic trifluoromethylselenation reagent, the reaction process is detected by conventional detection methods in the art (such as TLC, NMR or color change). Generally, the reaction end point is when a significant color change occurs, that is, the color of the reaction system changes from yellow to white. In the present invention, the reaction time is 10 minutes to 10 hours, preferably 10 minutes to 2 hours.

[0016] In the preparation process of the chlorotrifluoromethyl selenide in the preparation method of the electrophilic trifluoromethylselenation reagent: in an organic solvent, Compound 1b reacts with sulfonyl chloride to obtain chlorotrifluoromethyl selenide (ClSeCF3). The reaction equation in the preparation process is:

[0017]

[0018] In the preparation method of the chlorotrifluoromethyl selenide, the organic solvent is a conventional organic solvent for such reactions in the art, as long as it does not react with the reactants or products. In the present invention, ether solvents are preferred, and tetrahydrofuran is further preferred.

[0019] In the preparation method of the chlorotrifluoromethyl selenide, the volume-mass ratio of the organic solvent to Compound 1b is 0.5 mL / g to 50 mL / g, preferably 0.5 mL / g to 5 mL / g.

[0020] In the preparation method of the chlorotrifluoromethyl selenide, the molar ratio of sulfonyl chloride to Compound 1b is 1:0.5 to 1:10, preferably 1:0.5 to 1:3.

[0021] In the preparation method of the trifluoromethylseleno chloride described above, the reaction temperature is a conventional temperature in the art. The reaction temperature of the present invention is 0°C to 80°C, preferably 0°C to 50°C.

[0022] In the preparation method of the trifluoromethylseleno chloride described above, the progress of the reaction can be detected by conventional detection methods in the art (such as TLC, NMR or color change), and generally the reaction end point is when no raw material spot is detected by TLC. In the present invention, the reaction time is 5 minutes to 5 hours, preferably 5 minutes to 2 hours.

[0023] The preparation method of the electrophilic trifluoromethylselenation reagent in the present invention adopts the following synthetic route:

[0024]

[0025] The present invention also provides the application of the electrophilic trifluoromethylselenation reagent. The specific steps are as follows: in an organic solvent, the electrophilic trifluoromethylselenation reagent 1 and the alkynone methyl oxime compound 2 are subjected to an electrophilic cyclization reaction under the condition of a Lewis acid to obtain a 4-trifluoromethylselenoisoxazole compound. The reaction equation in the preparation process is;

[0026]

[0027] wherein, R 1 is phenyl, substituted phenyl or alkyl. The substituents of the substituted phenyl are one or more of C1-C8 alkyl, C1-C4 alkoxy or halogen; the alkyl is C1-C8 cyclic or chain alkyl; R 2 is phenyl, substituted phenyl, naphthyl, thienyl or alkyl. The substituents of the substituted phenyl are one or more of C1-C8 alkyl, halogen or cyano, and the alkyl is C1-C8 chain alkyl.

[0028] Based on the above conditions, the alkynone methyl oxime compound is any one of the following compounds:

[0029]

[0030] In the reaction of the electrophilic trifluoromethylseleno electrophilic reagent 1 and the alkynone methyl oxime compound 2, the organic solvent is a conventional organic solvent for this type of reaction in the art, as long as it does not react with the reactants or products. In the present invention, it is preferably one of nitrile solvents, halogenated hydrocarbon solvents, ether solvents, amide solvents or alcohol solvents, particularly preferably nitrile solvents, and further preferably acetonitrile.

[0031] In the reaction of the electrophilic trifluoromethylselenylation reagent 1 with alkynyl ketone methyl oxime compounds 2, the Lewis acid is a conventional Lewis acid for this type of reaction in the art. In the present invention, boron trifluoride diethyl ether, organic acids, inorganic acid anhydrides, metal salts (iron salts, aluminum salts, zinc salts, etc.) are preferred, and metal salts are particularly preferred, and ferric chloride is further preferred.

[0032] In the reaction of the electrophilic trifluoromethylselenylation reagent 1 with alkynyl ketone methyl oxime compounds 2, the volume-mass ratio of the organic solvent to the alkynyl ketone methyl oxime compound 2 is 1 mL / g to 200 mL / g, preferably 10 mL / g to 100 mL / g.

[0033] In the reaction of the electrophilic trifluoromethylselenylation reagent 1 with alkynyl ketone methyl oxime compounds 2, the molar ratio of the alkynyl ketone methyl oxime compound 2, the electrophilic trifluoromethylselenylation reagent 1 to the Lewis acid is 1:1:1 to 1:10:10, preferably 1:1:1 to 1:5:5.

[0034] In the reaction of the electrophilic trifluoromethylselenylation reagent 1 with alkynyl ketone methyl oxime compounds 2, the temperature is a conventional temperature for this type of reaction in the art. In the present invention, the reaction temperature is preferably 0 °C to 120 °C, and further preferably 30 °C to 100 °C.

[0035] In the reaction of the electrophilic trifluoromethylselenylation reagent 1 with alkynyl ketone methyl oxime compounds 2, the reaction process is detected by conventional detection methods in the art (such as TLC, NMR or HPLC), and generally the reaction end point is when no raw material spots are detected by TLC. In the present invention, the reaction time is 10 minutes to 10 hours, preferably 1 hour to 5 hours.

[0036] In the reaction of the electrophilic trifluoromethylselenylation reagent 1 with alkynyl ketone methyl oxime compounds 2, the corresponding prepared compound 3 is:

[0037]

[0038] Compared with the prior art, the present invention has the following advantages and beneficial effects: The present invention provides a novel electrophilic trifluoromethylselenylation reagent based on the phthalimide skeleton and its synthesis method. The electrophilic trifluoromethylselenylation reagent of the present invention can carry out an electrophilic cyclization reaction with alkynyl compounds to prepare compounds containing trifluoromethylselenyl groups, thereby realizing the introduction of the SeCF3 group into the compound, and finally constructing and synthesizing different types of trifluoromethylselenyl compounds with lipophilicity, which has broad application prospects in the fields of new drugs, pesticides, organic synthesis, etc. The electrophilic trifluoromethylselenylation reagent prepared by the present invention has high reaction efficiency, mild reaction conditions, high yield, wide range of applicable substrates and low production cost. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 1H, 13C, and 19F NMR spectra of Compound 1 in Example 1;

[0040] Figure 2 1H, 13C, and 19F NMR spectra of Compound 3a in Example 2;

[0041] Figure 3 1H, 13C, and 19F NMR spectra of Compound 3d in Example 3;

[0042] Figure 4 1H, 13C, and 19F NMR spectra of Compound 3h in Example 4;

[0043] Figure 5 1H, 13C, and 19F NMR spectra of Compound 3o in Example 5;

[0044] Figure 6 1H, 13C, and 19F NMR spectra of Compound 3r in Example 6;

[0045] Figure 7 1H, 13C, and 19F NMR spectra of Compound 3v in Example 7. Detailed Embodiments

[0046] The above content of the present invention will be further described in detail below through examples. However, it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples. All technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0047] Example 1

[0048] Preparation of Electrophilic Trifluoromethylselenation Reagent 1

[0049] Compound 1b (BnSeCF3) (10 mmol) was dissolved in anhydrous tetrahydrofuran (3.2 mL). Sulfuryl chloride (10 mmol) was added at room temperature, and the mixture was stirred at room temperature for 20 minutes. The solution turned orange-yellow. The reaction system was placed in a low-temperature environment at -78 °C. Dichloromethane (17 mL) was added to the reaction system, and Compound 1a (11 mmol, 1.1 equiv) was added. The reaction was continued at -78 °C for 1 - 2 hours. When the color of the reaction system changed from yellow to colorless, it was the end point of the reaction. The mixture was filtered (rinsed with DCM), and the filtrate was evaporated to dryness to obtain a solid, which was washed with petroleum ether and filtered by suction to obtain Compound 1 (yield: 75%) (containing 8% - 13% phthalimide by-products). Electrophilic trifluoromethylselenation reagent 1 is a white solid at room temperature.

[0050]

[0051] The NMR spectrum of the above Compound 1 is asFigure 1 as shown 1 H NMR(400MHz,DMSO)δppm 7.95 - 7.94(m,2H),7.90 - 7.89(m,2H). 13 C NMR(100MHz,DMSO)δppm 168.6,135.1,131.94,123.8,123.6(q,J=337Hz). 19 F NMR(376MHz,DMSO)δppm - 38.77.HRMS m / z Calcd for C9H4F3NNaO2Se:[M+Na] + =317.9252.Found:317.9253。

[0052] The application of Compound 1 as an electrophilic trifluoromethylselenation reagent 1 in the preparation of Compound 3 is as follows:

[0053] Example 2

[0054] Preparation of 3,5 - diphenyl - 4 - (trifluoromethylseleno)isoxazole (3a), and the structural formulas of Compounds 2a and 3a are as follows in sequence:

[0055]

[0056] Preparation method: Add Compound 1 (0.4 mmol, 2.0 equiv, 117.6 mg), Compound 2a (0.2 mmol, 47.0 mg, 1.0 equiv), and anhydrous ferric chloride (0.24 mmol, 1.2 equiv, 38.9 mg) into a reaction tube, then add 2 mL of anhydrous acetonitrile and react at 80 °C for 2 hours. After monitoring the reaction by TLC until completion, add 10 mL of saturated sodium bicarbonate solution and extract with ethyl acetate (2 x 15 mL). Dry the organic phase with anhydrous sodium sulfate, then concentrate the organic phase and purify it by column chromatography (PE:EtOAc = 20:1) to obtain the product as a white solid Compound 3a (72.1 mg, 98%). The melting point, NMR, and high - resolution mass spectrometry information are as follows:

[0057] mp: 130 - 132 °C. 1 H NMR(400MHz,CDCl3)δppm 8.12 - 8.09(m,2H),7.81 - 7.79(m,2H),7.55 - 7.51(m,6H). 1313C NMR (100 MHz, CDCl3) δ ppm 174.1, 165.6, 131.3, 130.1, 129.0, 128.8, 128.5, 128.2, 128.0, 126.6, 121.5 (q, J = 334 Hz), 91.7. 19 19F NMR (376 MHz, CDCl3) δ ppm -36.05. HRMS m / z Calcd for C 16 H 11 F3NOSe: [M + H] + = 369.9952. Found: 369.9958。

[0058] Example 3

[0059] Preparation of compound 3-phenyl-5-p-tolyl-4-trifluoromethylselenoisoxazole (3d), the structural formulas of compounds 2d and 3d are as follows in sequence:

[0060]

[0061] The preparation method refers to Example 2, where the dosage of reactants is modified as: compound 2d (0.2 mmol, 49.8 mg, 1.0 equiv), and other conditions are the same as in Example 2. The final product is white solid compound 3d (70.3 mg, 92%). Its melting point, NMR and high-resolution mass spectrometry information are as follows:

[0062] mp: 82 - 84 °C. 1 1H NMR (400 MHz, CDCl3) δ ppm 8.01 (d, J = 8.0 Hz, 2H), 7.80 - 7.77 (m,

[0063] 2H), 7.52 - 7.49 (m, 3H), 7.34 (d, J = 8.0 Hz, 2H), 2.44 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ ppm 174.2, 165.7, 141.9, 130.1, 129.5, 129.0, 128.5, 128.1, 123.9, 121.8 (q, J = 334 Hz), 91.1, 21.6. 19 19F NMR (376 MHz, CDCl3) δ ppm -36.13. HRMS m / z Calcd for C 17 H 12 F3NNaOSe: [M + Na] + = 405.9928. Found: 405.9936。

[0064] Example 4

[0065] Preparation of compound 3-phenyl-5-(4-chlorophenyl)-4-(trifluoromethylseleno)isoxazole (3h), the structural formulas of compounds 2h and 3h are as follows in sequence:

[0066]

[0067] The preparation method refers to Example 2, where the amounts of reactants are modified as follows: compound 2h (0.2 mmol, 53.9 mg, 1.0 equiv). Other conditions are the same as those in Example 2. The final product is light yellow solid 3h (75.7 mg, 94%). The melting point, NMR and high-resolution mass spectrometry information are as follows:

[0068] mp: 90 - 92 °C. 1 H NMR (400 MHz, CDCl3) δ ppm 8.08 (d, J = 8.8 Hz, 2H), 7.79 - 7.77 (m,

[0069] 2H), 7.53 - 7.51 (m, 5H). 13 C NMR (100 MHz, CDCl3) δ ppm 172.9, 165.8, 137.7, 130.2, 129.4, 129.2, 129.0, 128.6, 127.8, 125.1, 121.4 (q, J = 334 Hz), 92.0. 19 F NMR (376 MHz, CDCl3) δ ppm -35.93. HRMS m / z Calcd for C 16 H 10 ClF3NOSe: [M + H] + = 403.9563. Found: 403.9562.

[0070] Example 5

[0071] Preparation of compound 5-butyl-3-phenyl-4-(trifluoromethylseleno)isoxazole (3o), the structural formulas of compounds 2o and 3o are as follows in sequence:

[0072]

[0073] The preparation method refers to Example 2, where the amounts of reactants are modified as follows: compound 2o (0.2 mmol, 43.0 mg, 1.0 equiv). Other conditions are the same as those in Example 2. The final product is light yellow liquid 3o (62.6 mg, 90%). The NMR and high-resolution mass spectrometry information are as follows:

[0074] 11H NMR (400 MHz, CDCl3) δ ppm 7.82 - 7.80 (m, 2H), 7.49 - 7.46 (m, 3H), 3.01 (t, J = 8.0 Hz, 2H), 1.80 - 1.74 (m, 2H), 1.49 - 1.40 (m, 2H), 0.98 (t, J = 7.2 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ ppm 180.6, 163.7, 130.1, 128.6, 128.5, 128.1, 121.6 (q, J = 333 Hz), 92.8, 29.3, 26.3, 22.3, 13.6. 19 19F NMR (376 MHz, CDCl3) δ ppm -36.66. HRMS m / z Calcd for C 14 H 15 F3NOSe: [M + H] + = 350.0265. Found: 350.0252。

[0075] Example 6

[0076] Preparation of compound 3 - (p - methoxyphenyl) - 5 - phenyl - 4 - (trifluoromethylseleno)isoxazole (3r), and the structural formulas of compounds 2r and 3r are as follows in sequence:

[0077]

[0078] The preparation method refers to Example 2, where the amounts of reactants are modified as follows: compound 2r (0.2 mmol, 53.0 mg, 1.0 equiv). Other conditions are the same as in Example 2, and the final product is white solid 3r (51.9 mg, 95%). The melting point, NMR, and high - resolution mass spectrometry information are as follows:

[0079] mp: 85 - 87 °C. 1 1H NMR (400 MHz, CDCl3) δ ppm 8.10 - 8.07 (m, 2H), 7.79 - 7.77 (m, 2H), 7.54 - 7.53 (m, 3H), 7.04 - 7.02 (m, 2H), 3.87 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ ppm 174.1, 165.1, 161.0, 131.3, 130.4, 128.8, 128.2, 126.7, 121.5 (q, J = 334 Hz), 120.3, 114.0, 91.7, 55.3. 19 19F NMR (376 MHz, CDCl3) δ ppm -36.07. HRMS m / z Calcd for C17 H 13 F3NO2Se: [M+H] + = 400.0058. Found: 400.0061。

[0080] Example 7

[0081] Preparation of compound 3-cyclohexyl-5-phenyl-4-trifluoromethylselenoisoxazole (3w), and the structural formulas of compounds 2w and 3w are as follows in sequence:

[0082]

[0083] The preparation method refers to Example 2, where the amounts of reactants are modified as follows: compound 2w (0.2 mmol, 48.2 mg, 1.0 equiv). Other conditions are the same as in Example 2. The final product is white solid 3w (58.3 mg, 78%). The melting point, NMR, and high-resolution mass spectrometry information are as follows:

[0084] mp: 93 - 95 °C. 1 H NMR (400 MHz, CDCl3) δ ppm 8.07 - 8.04 (m, 2H), 7.51 - 7.48 (m, 3H), 2.95 - 2.88 (m, 1H), 2.01 (d, J = 13.2 Hz, 2H), 1.90 - 1.86 (m, 2H), 1.78 - 1.75 (m, 1H), 1.70 - 1.61 (m, 2H), 1.48 - 1.29 (m, 3H). 13 C NMR (100 MHz, CDCl3) δ ppm 172.7, 170.8, 128.7, 128.0, 126.8, 121.6 (q, J = 334 Hz), 91.9, 35.8, 31.8, 26.3, 25.9. 19 F NMR (376 MHz, CDCl3) δ ppm -36.1. HRMS m / z Calcd for C 16 H 16 F3NNaOSe: [M+Na] + = 398.0241. Found: 398.0257。

[0085] The above examples describe the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above examples. What is described in the above examples and the specification only illustrates the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. Use of an electrophilic trifluoromethylseleno reagent in the preparation of a trifluoromethylseleno-containing compound, characterized in that The specific steps are as follows: In an organic solvent, an electrophilic cyclization reaction is carried out between the electrophilic trifluoromethylselenyl reagent 1 and the alkynone methyl oxime compound 2 under the condition of a Lewis acid to obtain 4-trifluoromethylselenylisoxazole compounds. The reaction equation for the preparation process is as follows: ； Among them, R 1 is phenyl, substituted phenyl or alkyl. The substituents of the substituted phenyl are one or more of C1-C8 alkyl, C1-C4 alkoxy or halogen; the alkyl is C1-C8 cyclic or linear alkyl; R 2 is phenyl, substituted phenyl, naphthyl, thiophenyl or alkyl. The substituents of the substituted phenyl are one or more of C1-C8 alkyl, halogen or cyano, and the alkyl is C1-C8 linear alkyl; the Lewis acid is iron trichloride; the organic solvent is one of nitrile solvents, halogenated hydrocarbon solvents, amide solvents or alcohol solvents.

2. The application according to claim 1, wherein: The alkynone methyl oxime compound described is one of the following compounds: 。 3. The application according to claim 1, wherein: The volume-mass ratio of the organic solvent to the alkynone methyl oxime compound 2 is 10 mL / g to 100 mL / g. The molar ratio of the alkynone methyl oxime compound 2, the electrophilic trifluoromethylselenyl reagent 1 to the Lewis acid is 1:1:1 to 1:5:

5. The reaction temperature is 30 °C to 100 °C, and the reaction time is 1 hour to 5 hours.

4. The application according to claim 1, wherein: The 4-(trifluoromethylseleno)isoxazole compounds described above are one of the following compounds: .

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