3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound and preparation method thereof

Abstract

The invention discloses a 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound and a preparation method of the 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound. The synthesis of the 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound comprises the following steps: taking an alpha-trifluoromethyl styrene compound as an initial raw material, carrying out an alkyl allylation reaction catalyzed by visible light to obtain a 4-alkyl-4-aryl-5, 5, 5-trifluoro-1-pentene compound, oxidizing to obtain a 3-alkyl-3-aryl-4, 4, 4-trifluorobutyraldehyde compound, and carrying out a reaction on the 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound and the 4-alkyl-4-aryl-5, 5, 5-trifluoro-1-pentene compound to obtain the 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound. And finally, carrying out bromination and elimination reactions to obtain the 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound. The 3-alkyl-3-aryl-4, 4, 4-trifluoro-1-butyne compound provided by the invention can be used as a synthetic building block containing a corresponding structural unit, and the 4, 4, 4-trifluoro-1-butyne structural unit can be rapidly introduced into a drug molecule.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemical synthesis, and particularly relates to a 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound and a preparation method thereof. Background Art

[0002] The 4,4,4-trifluoro-1-butyne structure, as a unique structural unit, has important applications in the fields of medicine, materials, and synthetic chemistry. Especially as a key structural fragment in the anti-HIV drug efavirenz, it provides important medicinal activities. In recent years, further research has shown that the structural analogs of efavirenz possess more diverse biological activities (N. Mast, P. Verwilst, C. J. Wilkey, F. P. Guengerich, I. A. Pikuleva, J. Med. Chem. 2020, 63, 6477-6488), and 4,4,4-trifluoro-1-butyne is still the core fragment among them. Although the 4,4,4-trifluoro-1-butyne structural unit has important applications, there are still many problems in the construction of such structures. For example, the general steps are relatively long, and the functional group compatibility is limited, which is not conducive to the extensive research and application of this structure.

[0003]

[0004] First, as disclosed in Document 1 (M. Patel, R. J. McHugh Jr., B. C. Cordova, R. M. Klabe, L. T. Bacheler, S. Erickson-Viitanen, J. D. Rodgers Bioorg. Med. Chem. Lett. 2001, 11, 1943-1945), the 4,4,4-trifluoro-1-butyne fragment was constructed through a five-step reaction, in which an aluminum amalgam reagent was required. The specific reaction process is as follows:

[0005]

[0006] Second, as disclosed in Document 2 (A. Sanz-Marco, G. Blay, C. Vila, J. R. Pedro, Org. Lett. 2016, 18, 3538-3541), the Michael addition of alkynyl zinc to β-trifluoromethyl-α,β-unsaturated carbonyl compounds was used to obtain the product containing the 4,4,4-trifluoro-1-butyne fragment. The specific reaction process is as follows:

[0007]

[0008] Although the synthesis of 4,4,4-trifluoro-1-butyne structures has been reported, the steps are usually long and the substitution types are limited, making it difficult to meet the requirements for constructing diverse molecules. Given the important applications of compounds containing 4,4,4-trifluoro-1-butyne fragments in drug development, developing new methods for constructing 4,4,4-trifluoro-1-butyne fragments has good application prospects. This application provides a 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound and its synthesis method, which can be conveniently used for the synthesis of molecules with complex structures. Summary of the Invention

[0009] The purpose of this section is to outline some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of the present application, to avoid obscuring the purpose of this section, the abstract, and the title. However, such simplifications or omissions shall not be used to limit the scope of the present invention.

[0010] In view of the deficiencies of the existing synthesis steps of 4,4,4-trifluoro-1-butyne compounds, such as long steps and limited substituent types, this application provides a 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound and its synthesis method. Such compounds can also be used for the synthesis of molecules with complex structures to meet the requirements of specific biological activities.

[0011] This application provides a compound represented by the general formula (I):

[0012]

[0013] Wherein, R 1 is an aryl group or a heteroaryl group; R 2 is an alkyl group.

[0014] The 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound of the present invention is prepared by the following route:

[0015]

[0016] Using α-trifluoromethylstyrene compounds as starting materials, reacting with potassium allyltrifluoroborate and N-alkylacyloxyphthalimide under the catalysis of 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN). The reaction is carried out at room temperature under the irradiation of an LED lamp (wavelength 456 nm, power 15 W) to obtain 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene products. This compound can be oxidized to obtain 3-alkyl-3-aryl-4,4,4-trifluorobutyraldehyde, and then through deoxygenation bromination and elimination, 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compounds can be obtained. Based on this synthetic route, 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compounds containing different substituents can be obtained by adjusting the structures of α-trifluoromethylstyrene compounds and N-alkoxycarbonylphthalimide.

[0017] The compounds synthesized in the present invention can be prepared by a variety of synthetic methods well-known to those skilled in the art, including the specific embodiments listed below, the embodiments formed by their combination with other chemical synthesis methods, and the equivalent replacement methods well-known to those skilled in the art. Preferred embodiments include, but are not limited to, the examples of the present invention. Specific embodiments

[0018] The following examples are used to further describe the present application in detail, but the embodiments of the present application are not limited thereto.

[0019] Example 1: Synthesis of 4-(1-methylcyclohexyl)methyl-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4a

[0020]

[0021] Under an inert gas atmosphere, 2-(4-phenylphenyl)-3,3,3-trifluoropropene 1a (49.6 mg, 0.2 mmol), potassium allyltrifluoroborate 2 (59.2 mg, 0.4 mmol), N-(1-methylcyclohexyl)acyloxyphthalimide 3a (86.1 mg, 0.3 mmol) and 4CzIPN (1.6 mg, 0.002 mmol) were successively added to ethylene glycol dimethyl ether (1 mL) to obtain a mixture. Among them, the molar ratio of 1a, 2, 3a, and 4CzIPN is 1:2:1.5:0.01.

[0022] The above mixture was reacted under irradiation with an LED lamp (wavelength 456 nm, power 15 W) at room temperature for 24 hours. After the reaction, the solid precipitate was removed by filtration and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated by column chromatography to obtain 4-(1-methylcyclohexyl)methyl-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4a (73.4 mg, 0.19 mmol), a colorless oily compound, with a yield of 95%. The analytical data are as follows:

[0023] 1 H NMR (400 MHz, CDCl 3 ): δ 7.67 - 7.55 (m, 6H), 7.48 - 7.42 (m, 2H), 7.38 - 7.33 (m, 1H), 6.04 - 5.94 (m, 1H), 5.21 (ddd, J = 16.9, 1.6, 1.6 Hz, 1H), 5.12 (ddd, J = 10.2, 1.6, 1.6 Hz, 1H), 3.17 (dd, J = 15.3, 6.2 Hz, 1H), 2.83 (dd, J = 15.4, 7.2 Hz, 1H), 2.19 (d, J = 15.0 Hz, 1H), 1.99 (d, J = 15.0 Hz, 1H), 1.47 - 1.23 (m, 8H), 1.13 - 1.10 (m, 2H), 0.68 (s, 3H). 19 F NMR (376 MHz, CDCl 3 ): δ -66.51 (s, 3F). 13 C NMR (100 MHz, CDCl 3 ): δ 140.4, 139.9, 137.9, 134.4, 128.9, 128.7, 128.5 (q, J = 287.8 Hz), 127.6, 127.1, 126.7, 117.8, 52.3 (q, J = 21.6 Hz), 47.4, 40.6, 40.2, 39.8, 34.6, 26.2, 24.6, 22.0, 21.9. HRMS (ESI, m / z): calcd for C 25 H 30 F 3 , [M + H] + : 387.2294, found: 387.2295.

[0024] Example 2: Synthesis of 4-(1-methylcyclohexyl)methyl-4-(3-methoxycarbonylindol-1-yl)-5,5,5-trifluoro-1-pentene 4b

[0025]

[0026] Under an inert gas atmosphere, methyl N-(1-trifluoromethylvinyl)indole-3-carboxylate 1b (53.8 mg, 0.2 mmol), potassium allyltrifluoroborate 2 (59.2 mg, 0.4 mmol), N-(1-methylcyclohexyl)acyloxyphthalimide 3a (86.1 mg, 0.3 mmol), and 4CzIPN (1.6 mg, 0.002 mmol) were successively added to ethylene glycol dimethyl ether (1 mL) to obtain a mixture. Among them, the molar ratio of 1b, 2, 3a, and 4CzIPN was 1:2:1.5:0.01.

[0027] The above mixture was reacted under irradiation with an LED lamp (wavelength 456 nm, power 15 W) at room temperature for 24 hours. After the reaction was completed, the solid precipitate was filtered off and the solvent was removed by distillation under reduced pressure to obtain a crude product. The crude product was separated by column chromatography to obtain 4-(1-methylcyclohexyl)methyl-4-(3-methoxycarbonylindol-1-yl)-5,5,5-trifluoro-1-pentene 4b (46.4 mg, 0.11 mmol), a colorless oily compound, with a yield of 57%. The analytical data are as follows:

[0028] 1 H NMR (400 MHz, CDCl 3 ):δ8.29 - 8.22 (m, 1H), 8.19 (s, 1H), 7.74 - 7.68 (m, 1H), 7.31 - 7.23 (m, 2H), 6.05 - 5.94 (m, 1H), 5.34 (ddd, J = 16.9, 1.5, 1.5 Hz, 1H), 5.26 (ddd, J = 10.1, 1.6, 1.6 Hz, 1H), 3.92 (s, 3H), 3.49 (dd, J = 15.8, 7.2 Hz, 1H), 3.15 (dd, J = 15.8, 6.1 Hz, 1H), 2.79 (d, J = 15.7 Hz, 1H), 2.15 (d, J = 15.8 Hz, 1H), 1.48 - 1.27 (m, 8H), 1.12 (m, 2H), 0.49 (s, 3H). 19 F NMR (376 MHz, CDCl 3 ):δ - 69.62 (s, 3F). 13 C NMR (100 MHz, CDCl 3):δ 165.4, 137.4, 134.0, 131.4, 128.8 (q, J = 289.9 Hz), 127.9, 123.2, 122.2, 122.0, 120.3, 115.3 (q, J = 3.7 Hz), 108.4, 69.3 (q, J = 25.6 Hz), 51.3, 40.4, 39.8, 39.7, 34.1, 25.9, 21.8, 21.7. HRMS(ESI, m / z): calcd for C 23 H 29 F 3 NO 2 , [M + H] + : 408.2145, found: 408.2142.

[0029] Example 3: Synthesis of 4-(1-methylcyclohexyl)methyl-4-(4-methoxycarbonylphenyl)-5,5,5-trifluoro-1-pentene 4c

[0030]

[0031] Under an inert gas atmosphere, 2-(4-methoxycarbonylphenyl)-3,3,3-trifluoropropene 1c (46.0 mg, 0.2 mmol), potassium allyltrifluoroborate 2 (59.2 mg, 0.4 mmol), N-(1-methylcyclohexyl)acyloxyphthalimide 3a (86.1 mg, 0.3 mmol), and 2,4,5,6-tetrakis(9-carbazolyl)isophthalonitrile (4CzIPN) (1.6 mg, 0.002 mmol) were successively added to ethylene glycol dimethyl ether (1 mL) to obtain a mixture. Among them, the molar ratio of 1c, 2, 3a, and 4CzIPN is 1:2:1.5:0.01.

[0032] The above mixture was reacted under irradiation with an LED lamp (wavelength 456 nm, power 15 W) at room temperature for 36 hours. After the reaction, the solid precipitate was filtered off and the solvent was removed by distillation under reduced pressure to obtain a crude product, which was separated by column chromatography to obtain 4-(1-methylcyclohexyl)methyl-4-(4-methoxycarbonylphenyl)-5,5,5-trifluoro-1-pentene 4c (58.2 mg, 0.16 mmol), a colorless oily compound, with a yield of 79%. The analysis data are as follows:

[0033] 1 H NMR(400 MHz, CDCl 3):δ 7.99 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.3 Hz, 2H), 5.93 - 5.83 (m, 1H), 5.17 (ddd, J = 17.0, 1.7, 1.7 Hz, 1H), 5.09 (ddd, J = 10.2, 1.6, 1.6 Hz, 1H), 3.92 (s, 3H), 3.10 (dd, J = 15.4, 6.7 Hz, 1H), 2.79 (dd, J = 15.4, 7.2 Hz, 1H), 2.16 (d, J = 15. Hz, 1H), 1.98 (d, J = 15.2 Hz, 1H), 1.44 - 1.24 (m, 8H), 1.08 - 1.04 (m, 2H), 0.61 (s, 3H). 19 19F NMR (376 MHz, CDCl 3 ):δ -66.73 (s, 3F). 13 13C NMR (100 MHz, CDCl 3 ):δ 166.9, 144.2, 133.7, 129.4, 129.1, 126.8 (q, J = 287.0 Hz), 123.9, 118.3, 52.8 (q, J = 21.7 Hz), 52.3, 47.8, 40.6, 40.2, 40.1, 34.6, 26.1, 24.5, 22.0, 21.9. HRMS (ESI, m / z): calcd for C 21 21 28 19 3 1 2 , [M + H] + : 369.2036, found: 369.2040.

[0034] Example 4: Synthesis of 4-Cyclohexylmethyl-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4d

[0035]

[0036] Under an inert gas atmosphere, 2-(4-phenylphenyl)-3,3,3-trifluoropropene 1a (49.6 mg, 0.2 mmol), potassium allyltrifluoroborate 2 (59.2 mg, 0.4 mmol), N-cyclohexylcarbonyloxyphthalimide 3b (81.9 mg, 0.3 mmol), and 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN) (1.6 mg, 0.002 mmol) were successively added to ethylene glycol dimethyl ether (1 mL) to obtain a mixture. Among them, the molar ratio of 1a, 2, 3b, and 4CzIPN was 1:2:1.5:0.01.

[0037] The above mixture was reacted under irradiation with an LED lamp (wavelength 456 nm, power 15 W) at room temperature for 24 hours. After the reaction, the solid precipitate was removed by filtration and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated by column chromatography to obtain 4-cyclohexylmethyl-4-(4-phenyl)phenyl-5,5,5-trifluoro-1-pentene 4d (46.2 mg, 0.12 mmol), a colorless oily compound with a yield of 62%. The analytical data are as follows:

[0038] 1 H NMR (400 MHz, CDCl 3 ): δ 7.69 - 7.62 (m, 4H), 7.59 (d, J = 8.6 Hz, 2H), 7.51 - 7.46 (m, 2H), 7.42 - 7.35 (m, 1H), 5.94 - 5.82 (m, 1H), 5.23 (ddd, J = 17.0, 1.7, 1.7 Hz, 1H), 5.16 (ddd, J = 10.2, 1.6, 1.6 Hz, 1H), 3.02 (dd, J = 15.1, 6.9 Hz, 1H), 2.85 (dd, J = 15.1, 6.9 Hz, 1H), 2.02 (d, J = 1.8 Hz, 1H), 2.00 (d, J = 1.3 Hz, 1H), 1.75 - 1.56 (m, 4H), 1.52 - 1.42 (m, 2H), 1.24 - 0.99 (m, 4H), 0.94 - 0.81 (m, 1H). 19 F NMR (376 MHz, CDCl 3 ): δ -68.87 (s, 3F). 13 C NMR (100 MHz, CDCl 3 ): δ 140.4, 140.1, 137.4, 133.6, 128.9, 128.6, 128.5 (q, J = 285.9 Hz), 127.6, 127.1, 126.8, 118.5, 51.1 (q, J = 22.2 Hz), 40.9, 38.3, 35.5, 35.2, 33.5, 26.6, 26.5, 26.3. HRMS (ESI, m / z): calcd for C 24 H 28 F 3 , [M + H] + : 373.2138, found: 373.2133.

[0039] Example 5: Synthesis of 4-(3-phenylpropyl)-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4e

[0040]

[0041] Under an inert gas atmosphere, 2-(4-phenylphenyl)-3,3,3-trifluoropropene 1a (49.6 mg, 0.2 mmol), potassium allyltrifluoroborate 2 (59.2 mg, 0.4 mmol), N-(3-phenylpropyl)phthalimidoacetate 3c (59.0 mg, 0.3 mmol), and 2,4,5,6-tetrakis(9-carbazolyl)isophthalonitrile (4CzIPN) (1.6 mg, 0.002 mmol) were successively added to ethylene glycol dimethyl ether (1 mL) to obtain a mixture. Among them, the molar ratio of 1a, 2, 3c, and 4CzIPN was 1:2:1.5:0.01.

[0042] The above mixture was reacted under irradiation of an LED lamp (wavelength 456 nm, power 15 W) at room temperature for 24 hours. After the reaction, the solid precipitate was removed by filtration and the solvent was evaporated under reduced pressure to obtain a crude product. The crude product was separated by column chromatography to obtain 4-(3-phenylpropyl)-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4e (37.1 mg, 0.09 mmol), a colorless oily compound, with a yield of 47%. The analysis data are as follows:

[0043] 1 H NMR (400 MHz, CDCl 3 ):δ7.65 - 7.54 (m, 4H), 7.48 - 7.44 (m, 4H), 7.39 - 7.35 (m, 1H), 7.33 - 7.27 (m, 2H), 7.23 - 7.14 (m, 3H), 5.84 - 5.70 (m, 1H), 5.18 (ddd, J = 17.0, 1.6, 1.6 Hz, 1H), 5.12 (ddd, J = 10.1, 1.3, 1.3 Hz, 1H), 2.96 (dd, J = 14.9, 6.9 Hz, 1H), 2.76 (dd, J = 15.0, 7.4 Hz, 1H), 2.71 - 2.56 (m, 2H), 2.19 - 2.02 (m, 2H), 1.77 - 1.55 (m, 2H). 19 F NMR (376 MHz, CDCl 3 ):δ - 70.23 (s, 3F). 13 C NMR (100 MHz, CDCl 3 ):δ141.8, 140.4, 140.3, 136.5, 133.0, 128.9, 128.6, 128.6, 128.5, 127.6, 127.2, 127.0, 126.1, 128.3 (q, J = 285.1 Hz), 118.9, 50.2 (q, J = 22.6 Hz), 37.4, 36.3, 31.4, 25.2. HRMS(ESI, m / z): calcd for C26 H 25 F 3 , [M+Na] + : 417.1801, found: 417.1814.

[0044] Example 6: Synthesis of 4-(2,2-dimethylpropyl)-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4f

[0045]

[0046] Under an inert gas atmosphere, 2-(4-phenylphenyl)-3,3,3-trifluoropropene 1a (49.6 mg, 0.2 mmol), potassium allyltrifluoroborate 2 (59.2 mg, 0.4 mmol), N-pivaloyloxyphthalimide 3d (74.1 mg, 0.3 mmol) and 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN) (1.6 mg, 0.002 mmol) were successively added to ethylene glycol dimethyl ether (1 mL) to obtain a mixture. Among them, the molar ratio of 1a, 2, 3d, and 4CzIPN was 1:2:1.5:0.01.

[0047] The above mixture was reacted under irradiation with an LED lamp (wavelength 456 nm, power 15 W) at room temperature for 24 hours. After the reaction, the solid precipitate was filtered off and the solvent was removed by distillation under reduced pressure to obtain a crude product. The crude product was separated by column chromatography to obtain 4-(2,2-dimethylpropyl)-4-(4-phenylphenyl)-5,5,5-trifluoro-1-pentene 4f (63.7 mg, 0.18 mmol), a colorless oily compound, with a yield of 92%. The analytical data are as follows:

[0048] 1 H NMR (400 MHz, CDCl 3 ): δ 7.63 - 7.56 (m, 6H), 7.49 - 7.39 (m, 2H), 7.37 - 7.31 (m, 1H), 5.19 (ddd, J = 17.0, 1.7, 1.7 Hz, 1H), 5.11 (ddd, J = 10.2, 1.5, 1.5 Hz, 1H), 3.12 (dd, J = 15.1, 6.6 Hz, 1H), 2.81 (dd, J = 15.4, 7.1 Hz, 1H), 2.18 (d, J = 15.0 Hz, 1H), 2.01 (d, J = 15.0 Hz, 1H), 0.80 (s, 9H). 19 F NMR (376 MHz, CDCl 3 ): δ -67.29 (s, 3F). 13 C NMR (100 MHz, CDCl 3):δ 140.4, 140.1, 137.5, 134.2, 128.9, 128.7, 128.4 (q, J = 286.6 Hz), 127.6, 127.1, 126.7, 117.9, 52.2 (q, J = 21.5 Hz), 46.9, 39.5, 32.1, 32.0. HRMS(ESI, m / z): calcd for C 22 H 26 F 3 , [M + H] + : 347.1981, found: 347.1979.

[0049] Example 7: Synthesis of 3-(2,2-dimethylpropyl)-3-(4-phenyl)phenyl-4,4,4-trifluoro-1-butyraldehyde 5

[0050]

[0051] To a 10 mL reaction tube equipped with a magnetic stir bar, 4f (69.2 mg, 0.2 mmol), 2 mL of ethanol, 2 mL of water, and NaIO 4 (25.7 mg, 1.2 mmol) were successively added. After the reaction mixture was stirred at room temperature for 20 min, K 2 OsO 4 ·2H 2 O (36.8 mg, 0.01 mol) was added. The above mixture was stirred at room temperature for 19 h. After the reaction was completed, the organic phase was separated, and the aqueous phase was extracted with Et 2 O (3 x 10 mL). The combined organic phases were washed with saturated brine, dried over anhydrous Na 2 SO 4 , and the solvent was removed under reduced pressure to obtain the crude product. The product was separated by column chromatography to obtain 3-(2,2-dimethylpropyl)-3-(4-phenyl)phenyl-4,4,4-trifluoro-1-butyraldehyde 5 (41.8 mg, 0.12 mmol), a pale yellow oily compound, with a yield of 60%. The analytical data are as follows:

[0052] 1 H NMR (400 MHz ID CDCl 3):δ 9.91 - 9.87 (m, 1H), 7.65 - 7.59 (m, 4H), 7.56 (d, J = 8.3 Hz, 2H), 7.48 - 7.42 (m, 2H), 7.41 - 7.34 (m, 1H), 3.30 (dd, J = 16.6, 3.1 Hz, 1H), 3.05 (dd, J = 16.6, 2.3 Hz, 1H), 2.34 (d, J = 15.0 Hz, 1H), 2.15 (d, J = 15.0 Hz, 1H), 0.81 (s, 9H). 19 F NMR (376 MHz, CDCl 3 ):δ -70.36. (s, 3F). 13 C NMR (100 MHz, CDCl 3 ):δ 200.6, 140.9, 140.0, 136.0, 129.0, 128.2, 128.1 (q, J = 285.9 Hz), 127.8, 127.3, 127.1, 51.0 (q, J = 23.4 Hz), 47.0, 46.4, 32.1, 32.1. HRMS (ESI, m / z): calcd for C 21 H 25 F 3 O, [M + Na] + :371.1957, found: 371.1952.

[0053] Example 8: Synthesis of 3-(2,2-dimethylpropyl)-3-(4-phenylphenyl)-4,4,4-trifluoro-1-bromo-1-butene 6

[0054]

[0055] To a 10 mL reaction tube equipped with a magnetic stir bar was added tetrabutylammonium tribromide (0.137 mL, 0.44 mmol). After sealing and purging with nitrogen three times, dichloromethane (1 mL) was added. Under a nitrogen atmosphere, P(OPh) 3 (212.1 mg, 0.44 mmol) and 5 (139.1 mg, 0.4 mmol) were added sequentially via syringe. After stirring the above mixture at room temperature for 2 hours, the solvent was removed under reduced pressure. The crude product was separated by column chromatography to obtain 3-(2,2-dimethylpropyl)-3-(4-phenylphenyl)-4,4,4-trifluoro-1-bromo-1-butene 6 (82.0 mg, 0.2 mmol), a colorless oily compound, with a yield of 50%. The analytical data are as follows:

[0056] 1 H NMR (400 MHz, CDCl 3):δ 7.65 - 7.60 (m, 4H), 7.57 (d, J = 8.5 Hz, 2H), 7.50 - 7.44 (m, 2H), 7.41 - 7.36 (m, 1H), 6.61 (dq, J = 14.5, 1.4 Hz, 1H), 6.55 (dq, J = 14.5, 1.6 Hz, 1H), 2.49 (d, J = 14.8 Hz, 1H), 2.12 (d, J = 14.8 Hz, 1H), 0.90 (s, 9H). 19 F NMR (376 MHz, CDCl 3 ):δ -70.89 (s, 3F). 13 C NMR (100 MHz ID CDCl 3 ):δ 140.4, 139.9, 137.5, 128.9, 128.7 (q, J = 286.5 Hz), 128.6, 127.5, 127.10, 126.8, 63.4, 51.7 (q, J = 22.0 Hz), 47.9, 32.0, 31.3, 28.3. HRMS (ESI, m / z): calcd for C 21 H 22 BrF 3 , [M + H] + :411.0930, found: 411.0926.

[0057] Example 9: Synthesis of 3-(2,2-dimethylpropyl)-3-(4-phenylphenyl)-4,4,4-trifluoro-1-butyne 7

[0058]

[0059] To a 10 mL two-necked tube equipped with a magnetic stir bar, BuOK (67.3 mg, 0.6 mmol) and 18-crown-6 (2.6 mg, 0.01 mmol) were added successively. After sealing and purging with nitrogen three times, 5 mL of ultradry n-hexane and 6 (82.0 mg, 0.2 mmol) were added successively through a syringe, and the reaction was stirred at 80 °C for 12 h. After monitoring the completion of the reaction by TLC plate, the reaction was cooled to room temperature, quenched with water, and the organic phase was separated. The aqueous layer was extracted with n-hexane (2 x 10 mL), and the combined organic phases were washed with saturated brine and then dried over anhydrous Na t SO 2 SO 4 . The solvent was removed under reduced pressure. The crude product was purified by silica gel column chromatography to give 3-(2,2-dimethylpropyl)-3-(4-phenylphenyl)-4,4,4-trifluoro-1-butyne 7 (60.1 mg, 0.18 mmol), a colorless oily compound, with a yield of 91%. The analytical data are as follows:

[0060] 1 1H NMR (400 MHz, CDCl 3 3): δ 7.84 (d, J = 8.1 Hz, 2H), 7.67 - 7.59 (m, 4H), 7.48 - 7.44 (m, 2H), 7.41 - 7.33 (m, 1H), 2.74 (s, 1H), 2.37 (d, J = 14.3 Hz, 1H), 2.21 (d, J = 14.3 Hz, 1H), 0.88 (s, 9H). 19 19F NMR (376 MHz, CDCl 3 3): δ -73.82 (s, 3F). 13 13C NMR (100 MHz, CDCl 3 3): δ 141.2, 140.3, 133.6, 129.1, 129.0, 127.7, 127.2, 126.9, 126.0 (q, J = 284.7 Hz), 80.3, 78.3, 50.4 (q, J = 26.0 Hz), 44.7, 31.7, 31.6. HRMS (ESI, m / z): calcd for C 21 18 21 3 3 , [M+Na] + +: 353.1488, found: 353.1488.

[0061] Advantages of the present invention:

[0062] The present invention provides a 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound and a preparation method thereof. The raw materials used are simple and easily available, and the cost is low; the reaction conditions are mild, and the synthesis steps are simple; it can be used for the rapid construction of 4,4,4-trifluoro-1-butyne compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts. Among them:

[0064] Figure 1 is the 1H NMR spectrum of 4f in the embodiment of the present invention.

[0065] Figure 2 is the 13C NMR spectrum of 4f in the embodiment of the present invention.

[0066] Figure 3 is the 1H NMR spectrum of 5 in the embodiment of the present invention.

[0067] Figure 4 This is the carbon-13 NMR spectrum of 5 in the embodiments of the present invention.

[0068] Figure 5 This is the proton NMR spectrum of 6 in the embodiments of the present invention.

[0069] Figure 6 This is the carbon-13 NMR spectrum of 6 in the embodiments of the present invention.

[0070] Figure 7 This is the proton NMR spectrum of 7 in the embodiments of the present invention.

[0071] Figure 8 This is the carbon-13 NMR spectrum of 7 in the embodiments of the present invention.

Claims

1. A 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound, characterized in that: The chemical structure of the compound is as follows: Among them, R 1 are independently selected from aryl and heteroaryl; R 2 Independently selected from alkyl groups.

2. The method for preparing the 3-alkyl-3-aryl-4,4,4-trifluoro-1-butyne compound according to claim 1, characterized in that: The key steps include: Under an inert gas atmosphere, 2-aryl-3,3,3-trifluoropropene compound, potassium allyl trifluoroborate, N-alkyl acyloxyphthalimide and photocatalyst are sequentially added to a solvent to obtain a mixture, wherein the molar ratio of 2-aryl-3,3,3-trifluoropropene compound, potassium allyl trifluoroborate, N-alkyl acyloxyphthalimide and photocatalyst is 1:2:1.5:0.

01. The mixture is reacted at room temperature under LED light irradiation, and 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene product is collected from the reaction product.

3. The method for preparing the 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene compound according to claim 2, characterized in that: The photocatalyst is 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (4CzIPN).

4. The method for preparing the 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene compound according to claim 2, characterized in that: The solvent is one of ethylene glycol dimethyl ether and tetrahydrofuran.

5. The method for preparing the 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene compound according to claim 2, characterized in that: The inert gas is one of nitrogen and argon.

6. The method for preparing the 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene compound according to claim 2, characterized in that: The wavelength of the LED lamp is 450-460nm.

7. The method for preparing the 4-alkyl-4-aryl-5,5,5-trifluoro-1-pentene compound according to claim 2, characterized in that: The reaction time is 24 to 36 hours.

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