Preparation method of alpha-trifluoromethyl alkenyl indole compound

Abstract

The invention belongs to the technical field of organic synthesis, and particularly discloses a preparation method of an alpha-trifluoromethyl alkenyl indole compound, which comprises the following steps: by taking o-halogenated aniline and beta-CF3-1, 3-eneyne as raw materials, stirring and reacting at 80-110 DEG C for 12-24 hours under the action of a palladium catalyst, a ligand and alkali, thereby obtaining the alpha-trifluoromethyl alkenyl indole compound. The alpha-trifluoromethyl alkenyl indole compound with high regioselectivity is obtained. The method shows good tolerance to various functional groups such as halogens, ester groups, amino groups, keto groups, nitryl groups, cyano groups, heterocyclic rings and the like, the reaction can be smoothly carried out no matter the substrate is provided with an electron donating group or an electron withdrawing substituent group, the regioselectivity ratio can reach 2: 1 to 14: 1, and the yield of the alpha-CF3-alkenyl indole derivative reaches up to 80% or above. Meanwhile, the compound shows photochromic performance, and is relatively good in reaction performance.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of α-trifluoromethyl vinyl indole compounds. Background Art

[0002] The indole ring widely exists in natural products, drugs and other bioactive compounds, and is an important structural unit for their biological activities. Among many methods for synthesizing indoles, the Larock indole synthesis method uses o-haloaniline and substituted alkynes as raw materials to prepare indole compounds through ring closure. Among them, the raw material substituted alkyne can be a symmetric internal alkyne or an asymmetric internal alkyne.

[0003] As is well known, the incomplete addition reaction of asymmetric internal alkynes has regioselectivity and stereoselectivity, that is, the asymmetric internal alkyne may undergo a cis addition reaction or a trans addition reaction during addition. Therefore, when using an asymmetric internal alkyne as a raw material, two pairs of isomeric indole compounds will be obtained, resulting in problems such as low yield of the target product and difficulty in separating and purifying the product. Therefore, in the Larock indole synthesis method, terminal or symmetric alkynes are usually used to improve the regioselectivity problem, but the range of the obtained indole compounds is very limited. Summary of the Invention

[0004] To solve the above problems, the present invention provides a preparation method of α-trifluoromethyl vinyl indole compounds. By using a highly regioselective Larock indole synthesis method induced by fluorine effect, the construction of α-CF3-α-indolyl olefins that are difficult to synthesize by conventional methods is realized by using β-CF3-1,3-enyne. This method uses o-haloaniline and β-CF3-1,3-enyne as raw materials, and under the action of a palladium catalyst, a ligand, and a base, is stirred and reacted at 80-110 °C for 12-24 h to obtain a highly regioselective α-trifluoromethyl vinyl indole compound shown in formula (3).

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

[0006] A preparation method of α-trifluoromethyl vinyl indole compounds, the reaction formula of which is shown in (1), includes the following steps: Under the protection of an inert gas, to a mixture of a palladium catalyst, a ligand, a base, and an aniline shown in formula (1), add a β-CF3-1,3-enyne shown in formula (2) and 1,2-dichloroethane, stir and react at 80-110 °C for 12-24 h, and obtain an α-trifluoromethyl vinyl indole compound shown in formula (3) through separation and purification;

[0007] Wherein, X is I or Br; R1 is hydrogen, alkyl, alkoxy, haloalkyl, benzyloxy, halogen, cyano, nitro, alkanoyl, alkylamino or ester; R2 is acetyl, benzoyl, benzyl, phenyl or tert-butylformyl; R3 is phenyl, substituted phenyl, naphthyl or aromatic heterocyclyl, wherein the substituent in the substituted phenyl is hydrogen, alkyl, alkoxy, halogen, cyano, nitro, alkanoyl or ester.

[0008]

[0009] In one embodiment of the present invention, preferably, the process further comprises filtering, concentrating under reduced pressure, and separating by column chromatography after the reaction is completed to obtain an α-trifluoromethylvinyl indole compound as shown in formula (3), wherein the eluent is petroleum ether / ethyl acetate = 10-50:1.

[0010] In one embodiment of the present invention, preferably, the palladium catalyst is palladium acetate, palladium trifluoroacetate, tetrakistriphenylphosphine palladium or bis(acetonitrile)palladium dichloride; more preferably, the palladium catalyst is palladium acetate or palladium trifluoroacetate.

[0011] In one embodiment of the present invention, preferably, the base is sodium carbonate, cesium carbonate, potassium carbonate, potassium acetate, potassium phosphate, N,N-diisopropylethylamine or triethylamine; more preferably, the base is potassium phosphate.

[0012] In one embodiment of the present invention, the ligand is preferably a phosphine ligand or a nitrogen heterocyclic carbene ligand, wherein the phosphine ligand is 1,1′-binaphthyl-2,2′-bisdiphenylphosphine (BINAP), 1,1′-bis(diphenylphosphino)ferrocene (dppf), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos), 1,2-bis(diphenylphosphino)ethane (dppe), 1,2-bis(diphenylphosphino)ethane (dp pp), tricyclohexylphosphine (Cy3P), tri-tert-butylphosphine (t-Bu3P), 2-di-tert-butylphosphino-2′, 4′, 6′-triisopropylbiphenyl (t-BuXPhos) or tri-tert-butylphosphine tetrafluoroborate (t-Bu3PHBF4), the nitrogen heterocyclic carbene ligand is 1,3-bis(2,6-diisopropylphenyl)imidazolium hydrochloride (SIPrHCl); more preferably, the ligand is BINAP or dppp.

[0013] In one embodiment of the present invention, preferably, the feed ratio of aniline represented by formula (1), β-CF3-1,3-enyne represented by formula (2), palladium catalyst, base and ligand is 1.1-2.5:1:0.05-0.2:1-2:0.05-0.2.

[0014] The present invention also provides an α-trifluoromethylvinyl indole compound prepared by the above preparation method.

[0015] The present invention also provides the application of the above-mentioned α-trifluoromethylvinyl indole compounds in photochromic materials, including applications in high-intensity light radiation dosimeters, information storage elements, anti-counterfeiting, decorative and protective packaging materials.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] A preparation method of an α-trifluoromethylvinyl indole compound of the present invention synthesizes Larock indole through fluorine effect-induced regioselectivity. This method uses β-CF3-1,3-enyne as a raw material to achieve the 3,4-difunctionalization of β-CF3-1,3-enyne and successfully synthesizes α-CF3-vinyl indole derivatives. This method shows good tolerance to various functional groups such as halogens, ester groups, amino groups, ketone groups, nitro groups, cyano groups and heterocycles. Whether the substrate has an electron-donating group or an electron-withdrawing substituent, the reaction can proceed smoothly, and the regioselectivity ratio can reach 2:1 to 14:1, and the yield of the α-CF3-vinyl indole derivative is as high as over 80%. In addition, the present invention also discovers that the α-CF3-vinyl indole derivative has photochromic properties, and CF3 has an important regulatory effect on its derivatization reaction. For example, hydroboration and hydrobromination show regioselective reactions. Therefore, in view of the important positions of trifluoromethyl and indole skeletons in medicinal chemistry and materials science, the organic combination of the two will show broad application prospects in related fields. Description of the Drawings

[0018] Figure 1 1H NMR spectrum of 1-(3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (3a) for Example 1 1 1H NMR spectrum;

[0019] Figure 2 1H NMR spectrum of 1-(2-(4-methoxyphenyl)-3-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (4a) for Example 1

[0020] Figure 3 X-ray structure and crystal data of 1-(3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (3a) for Example 1

[0021] Figure 4 X-ray structure and crystal data of 1-(2-(4-methoxyphenyl)-3-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (4a) for Example 1

[0022] Figure 5 Schematic diagram of the experimental results for verifying the regioselectivity of the internal alkyne by CF3 in Example 2;

[0023] Figure 6 Schematic diagram of photoexcitation after deacetylation of Compounds 3a and 4a in Example 5;

[0024] Figure 7 Schematic diagram of the derivatization experiment of 1-(3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (3a) in Example 6. Detailed implementation manners

[0025] To make the above objects, features and advantages of the present invention more obvious and understandable, the following detailed description of the specific implementation manners of the present invention will be given with reference to the accompanying drawings.

[0026] In the following description, many specific details are set forth in order to fully understand the present invention. However, the present invention can be implemented in many other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the connotation of the present invention. Therefore, the present invention is not limited by the specific implementations disclosed below.

[0027] Unless otherwise specified, the chemical reagents used in the present invention, such as palladium catalysts, ligands, bases, organic solvents, etc., can be obtained by commercial means and do not require further purification when used.

[0028] The aniline shown in Formula (1) can be prepared according to the method disclosed in the literature Benedí, C.; Bravo, F.; Uriz, P.; Femández, E.; Claver, C.; Castillón, S., Tetrahedron lett. 2003, 44, 6073.

[0029] The β-CF3-1,3-enyne shown in formula (2) can be prepared according to the methods disclosed in the following literature: 1) Hu, C.-M.; Hong, F.; Xu, Y.-Y., J. Fluorine Chem. 1993, 64, 1. 2) Trost, B.M.; Debien, L, J. Am. Chem. Soc. 2015, 137, 11606. 3) Chen, S.; Zhang, J.; Yang, M.; Liu, F.; Xie, Z.; Liu, Y.; Lin, W.; Wang, D.; Li, X.; Wang, J., Chem. Commun. 2019, 55, 3879. The method for preparing the raw material of the β-CF3-1,3-enyne shown in formula (2) in this invention is as follows: PdCl2(PPh3)2 (0.01 equiv.) and CuI (0.02 equiv.) are successively added to a dried Schlenk flask equipped with a magnetic stir bar. The flask is evacuated and refilled with argon three times, and then dry THF, Et3N, alkyne (3 equiv.) and 2-bromo-3,3,3-trifluoroprop-1-ene (1.3 equiv.) are added. The reaction mixture is stirred in an oil bath at 50 °C for 12 hours, then the reaction is cooled to room temperature, quenched with saturated NH4Cl and extracted with EA. The combined organic phases are dried over Na2SO4. After evaporation under vacuum, the residue is purified by flash column chromatography on silica gel (PE∶EA = 10∶1) to obtain the β-CF3-1,3-enyne shown in formula (2).

[0030] Example 1 Optimization of reaction conditions

[0031]

[0032] 1.1 First, the influence of the reaction solvent on the reaction was investigated. By using the single variable method, 1,2-dichloroethane, toluene, chlorobenzene and acetone were used as the reaction solvents respectively.

[0033] Using N-(2-iodophenyl)acetamide (1a) and 1-methoxy-4-(3-(trifluoromethyl)but-3-en-1-yn-1-yl)benzene (2a) as raw materials. Under the protection of argon, first add 10% mol Pd(OAc)2, 10% mol BINAP, 0.6 mmol cesium carbonate and 0.6 mmol compound 1a to a dry Schlenk flask and mix them, then add 0.3 mmol compound 2a and 3 mL of organic solvent, place it in an oil bath and stir at 110 °C for 24 hours. After the reaction is completed, cool it to room temperature, filter through diatomaceous earth, remove the solvent with a rotary evaporator, and purify the crude product by silica gel column chromatography. The eluent is petroleum ether / ethyl acetate = 20:1. Among them, when only 1,2-dichloroethane is used as the reaction solvent, after purification by column chromatography, 1-(3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (3a) and 1-(2-(4-methoxyphenyl)-3-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (4a) are obtained, with a total yield of 56%, and the regio-selective compound 3a:compound 4a is 5:1; when toluene, chlorobenzene and acetone are used as the reaction solvent, the product compound 3a or compound 4a is not obtained. As shown in Table 1, items 1-4, the experiment shows that DCE should be used as the reaction solvent.

[0034] By 1 measuring the chemical shift difference of the terminal olefin hydrogens of compounds 3a and 4a by 1H NMR, the regioselectivity was determined. At the same time, under single-crystal X-ray diffraction analysis, the structures of compounds 3a and 4a were further confirmed, as Figure 3 shown.

[0035] 1-(3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (3a): yellow solid, 82.3 mg, 46.7%. m.p. 104 - 106 °C. As Figure 1 shown, 1 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.4 Hz, 1H), 7.51 (dd, J = 7.9, 1.2 Hz, 1H), 7.48 - 7.44 (m, 1H), 7.34 - 7.32 (m, 3H), 7.01 (d, J = 8.7 Hz, 2H), 6.11 (d, J = 1.3 Hz, 1H), 5.70 (d, J = 1.1 Hz, 1H), 3.90 (s, 3H), 2.76 (s, 3H); 13CNMR (101 MHz, CDCl3) δ 169.8, 159.2, 135.8, 132.3 (q, J = 32.9 Hz), 131.3, 130.0, 127.5, 127.2, 126.5 (q, J = 4.0 Hz), 126.1, 124.0, 123.6, 122.5 (q, J = 275.0 Hz), 120.9, 115.1, 113.9, 55.3, 27.2 ppm; 19 F NMR (377 MHz, CDCl3) δ -64.37 ppm; HRMS (ESI) m / z calcd for C 20 H 17 F3NO2 (M + H) + : 360.1206, found: 360.1218.

[0036] 1-(2-(4-Methoxyphenyl)-3-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (4a): Yellow liquid, 16.5 mg, 9.3%. As Figure 2 shown, 1 H NMR (400 MHz, CDCl3) δ 8.45 (dt, J = 8.4, 0.9 Hz, 1H), 7.54 (ddt, J = 7.7, 1.5, 0.8 Hz, 1H), 7.43 (ddd, J = 8.5, 7.2, 1.4 Hz, 1H), 7.38 - 7.31 (m, 1H), (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 6.11 (q, J = 1.4 Hz, 1H), 5.51 (q, J = 1.3 Hz, 1H), 3.90 (s, 3H), 2.02 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 171.4, 160.2, 137.9, 136.2, 131.7, 131.5 (q, J = 33.3 Hz), 128.9, 126.3 (q, J = 4.9 Hz), 125.6, 124.1, 124.0, 122.9 (q, J = 274.3 Hz), 119.6 (q, J = 2.2 Hz), 116.2, 116.1, 114.1, 55.3, 27.8 ppm; 19 F NMR (377 MHz, CDCl3) δ -65.93 ppm; HRMS (ESI) m / z calcd for [C 20 H 17 F3NO2 + H] + : 360.1206, found: 360.1221.

[0037] 1.2 To investigate the influence of ligands on the reaction, the single-variable method was adopted. Using bidentate phosphine ligands (dppf, Xantphos, dppe, dppp), monophosphine ligands (Cy3P, t-Bu3P, t-BuXPhos or t-BuPHBF4), and N-heterocyclic carbene ligand (5IPrHCl) as reaction ligands respectively, with DCE as the solvent and other reaction conditions the same as in 1.1.

[0038] As shown in Table 1, entries 5 - 12, the ligand dppp was preferred with a regioselectivity of 5:1 and the total yield increased to 82%. Monophosphine ligands and N-heterocyclic carbene ligands were inferior to the ligand dppp both in terms of regioselectivity and total yield. Experiments showed that the ligand dppp was the best reaction ligand.

[0039] 1.3 To investigate the influence of bases on the reaction, the single-variable method was adopted. Using Na2CO3, K2CO3, Li2CO3, Et3N, K3PO4 as bases respectively, with DCE as the solvent, dppp as the ligand, and other reaction conditions the same as in 1.1.

[0040] As shown in Table 1, entries 13 - 17, K3PO4 was preferred with a regioselectivity of 5:1 and the total yield increased to 88%. Among them, organic bases were inferior to inorganic bases. Experiments showed that K3PO4 was the best base for the reaction.

[0041] 1.4 To investigate the influence of palladium ligands on the reaction, the single-variable method was adopted. Using Pd(TFA)2, Pd(MeCN)2Cl2 or Pd(PPh3)4 as palladium ligands respectively, with DCE as the solvent, dppp as the ligand, K3PO4 as the base, and other reaction conditions the same as in 1.1.

[0042] As shown in Table 1, entries 18 - 20, Pd(OAc)2 and Pd(TFA)2 could obtain regioselectivities of 5:1 and 4:1 respectively, and the total yields were both increased to 88%. Considering the cost of raw materials, Pd(OAc)2 was selected as the palladium ligand for the reaction.

[0043] In addition, as shown in Table 1, entries 21 - 23, it was shown that palladium catalyst, ligand and base were crucial for the success of the reaction and none of them could be absent. Therefore, the reaction conditions of the present invention were: using DCE as the reaction solvent, in the presence of Pd(OAc)2 and dppp ligand, and using K3PO4 as the base was the optimal condition.

[0044] On this basis, Example 1 also investigated the effects of temperature and reaction time on the reaction. When the reaction temperature was 50 °C, the total yield was only 20%, and the regioselectivity of compound 3a: compound 4a was 5:1. When the reaction temperature was 90 °C, the total yield was 60%, and the regioselectivity of compound 3a: compound 4a was 5:1. Therefore, the reaction temperature was determined to be 110 °C. When the reaction time was 12 h, the total yield was 65%, and the regioselectivity of compound 3a: compound 4a was 5:1. The reaction time was determined to be 24 h.

[0045] Table 1

[0046]

[0047] Example 2

[0048] The β-CF3-1,3-enyne shown in formula (2) belongs to an asymmetric internal alkyne and undergoes a Larock indole synthesis reaction with the aniline shown in formula (1). From the perspective of structural properties, there are the following two problems for this β-CF3-1,3-enyne to participate in the Larock indole synthesis reaction: 1) There is a competitive reaction between the double bond and the triple bond, making it difficult to control the chemoselectivity; 2) The problem of difficult regulation of the high regioselectivity of internal alkynes. However, the present invention finds that CF3 plays an important role in controlling the regioselectivity of internal alkynes. When alkynes substituted with other groups (methyl, phenyl, trimethoxy, methoxycarbonyl) are placed under the reaction conditions determined in Example 1, the experimental results are as Figure 5 shown. When 2-methyl or 2-phenyl-enyne was used, yields of 67% and 14% were obtained with the non-regioselective mixtures 5a, 5a′ and 5b, 5b′ in a ratio of 1:1 and 1:4, respectively. Using 2-C(OMe)3-enyne as the substrate, a similar regioselectivity (5:1) and a yield of 51% were obtained, indicating that the steric hindrance and electron-withdrawing ability of CF3 are similar to those of C(OMe)3. When 2-ester benzene and 1-phenyl-2-formyl benzene were used, no products were detected. The products were analyzed by 1 1H NMR. The disappearance of the terminal alkene protons in the enyne indicates that the enyne was completely consumed. It is speculated that the possible reason is that strong electron-withdrawing groups (CO2Me, CHO) promoted the corresponding Heck reaction, thus inhibiting the functionalization of alkynes. The above results show that the fluorine effect of CF3 does play a crucial role in controlling the regioselectivity and balancing the reactivity of alkenes and alkynes.

[0049] Example 3 investigated the substrate applicability of the β-CF3-1,3-enyne shown in formula (2).

[0050]

[0051] Using N-(2-iodophenyl)acetamide (1a) and β-CF3-1,3-enyne shown in formula (2) as starting materials. Under the protection of argon, first add 10% mol Pd(OAc)2, 10% dppp ligand, 0.6 mmol K3PO4 and 0.6 mmol N-(2-iodophenyl)acetamide (1a) to a dry Schlenk flask and mix them. Then add 0.3 mmol of β-CF3-1,3-enyne shown in formula (2) and 3 mL of DCE, place it in an oil bath and stir at 110 °C for 24 hours. After the reaction is completed, cool it to room temperature, filter through diatomaceous earth, remove the solvent with a rotary evaporator, and purify the crude product by silica gel column chromatography. The eluent is petroleum ether / ethyl acetate to obtain the α-trifluoromethylvinyl indole compounds shown in formula (3), as shown in Table 2.

[0052] Table 2

[0053]

[0054] 1-(3-Phenyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3b): The regioselectivity ratio is 9:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 79%, 78.3 mg, m.p. 102 - 104 °C. 1H NMR (400 MHz, CDCl3) δ 8.11 (dt, J = 8.4, 0.9 Hz, 1H), 7.54 - 7.41 (m, 7H), 7.33 (ddd, J = 8.0, 7.2, 1.0 Hz, 1H), 6.11 (q, J = 1.3 Hz, 1H), 5.72 (q, J = 1.0 Hz, 1H), 2.78 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.9, 135.8, 132.2 (q, J = 32.8 Hz), 132.0, 130.2, 129.8, 128.5, 127.8, 127.6, 127.5, 126.6 (q, J = 4.2 Hz), 126.2, 123.7, 122.5 (q, J = 275.0 Hz), 120.9, 115.1, 27.2 ppm; 19 F NMR (377 MHz, CDCl3) δ -64.35 ppm; HRMS (ESI) m / z calcd for [C 19 H 14 NOF3 + H] + : 330.1100, found: 330.1103.

[0055] 1-(3-(p-Tolyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3c): The regioselectivity ratio was 5:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 83%, 85 mg, m.p. 104 - 106 °C. 1 H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 1H), 7.55 (dt, J = 7.8, 1.0 Hz, 1H), 7.48 (ddd, J = 8.6, 7.2, 1.3 Hz, 1H), 7.34 (t, J = 6.0 Hz, 5H), 6.13 (q, J = 1.3 Hz, 1H), 5.74 (d, J = 1.1 Hz, 1H), 2.79 (s, 3H), 2.48 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.9, 137.6, 135.9, 132.3 (q, J = 32.8 Hz), 130.03, 129.96, 129.2, 128.9, 127.54, 127.49, 126.6 (q, J = 4.0 Hz), 126.2, 123.6, 122.6 (q, J = 275.0 Hz), 120.9, 115.2, 27.2, 21.3 ppm; 19 F NMR (377 MHz, CDCl3) δ -65.90 ppm; HRMS (ESI) m / z calcd for [C20H16NOF3 + H] + : 344.1257, found: 344.1255.

[0056] 1-(3-(4-tert-Butylphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3d): The regioselectivity ratio was 3:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 62%, 72 mg, m.p. 100 - 102 °C. 1 H NMR (400 MHz, CDCl3) δ 8.11 (dd, J = 8.4, 0.9 Hz, 1H), 7.57 (dt, J = 7.7, 1.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.47 (ddd, J = 8.5, 7.2, 1.3 Hz, 1H), 7.37 (d, J = 8.4 Hz, 2H), 7.32 (ddd, J = 8.0, 7.2, 0.9 Hz, 1H), 6.13 (q, J = 1.3 Hz, 1H), 5.74 (d, J = 1.0 Hz, 1H), 2.78 (s, 3H), 1.43 (s, 9H); 1313C NMR (101 MHz, CDCl3) δ 169.9, 150.6, 135.9, 132.2 (q, J = 32.8 Hz), 130.0, 129.7 (2C), 128.8, 127.5, 126.6 (q, J = 3.9 Hz), 126.1, 125.4 (3C), 123.6, 122.6 (q, J = 275.1 Hz), 121.0, 115.1, 34.7, 31.4, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.30 ppm; HRMS (ESI) m / z calcd for 23 C 22 H + NOF3 + H]

[0057] 1-(3-(4-Chlorophenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3e): The regioselectivity ratio was 2:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 55%, 60.4 mg, m.p. 115 - 117 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.09 (d, J = 8.8 Hz, 1H), 7.50 - 7.45 (m, 4H), 7.37 - 7.32 (m, 3H), 6.12 (q, J = 1.3 Hz, 1H), 5.70 (d, J = 1.1 Hz, 1H), 2.77 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.8, 135.8, 133.9, 132.1 (q, J = 33.0 Hz), 131.4, 130.5, 129.5, 128.8, 127.8, 126.8 (q, J = 4.1 Hz), 126.3, 126.1, 123.8, 122.4 (q, J = 274.6 Hz), 120.6, 115.2, 27.1 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.37 ppm; HRMS (ESI) m / z calcd for 19 C 13 H + NOF3Cl + H]

[0058] 1-(3-(4-Fluorophenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3f): The regioselectivity ratio is 5:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 66%, 68.2 mg, m.p. 88 - 90 °C. 1 H NMR (400 MHz, CDCl3) δ 8.11 - 8.09 (m, 1H), 7.50 - 7.46 (m, 2H), 7.42 - 7.37 (m, 2H), 7.36 - 7.32 (m, 1H), 7.20 - 7.16 (m, 2H), 6.13 (q, J = 1.3 Hz, 1H), 5.71 (q, J = 1.0 Hz, 1H), 2.78 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.8, 162.4 (d, J = 247.1 Hz), 135.7, 132.2 (q, J = 33.0 Hz), 131.8 (d, J = 8.1 Hz), 129.7, 127.9 (d, J = 3.4 Hz), 127.8, 126.7 (q, J = 4.1 Hz), 126.33, 126.28, 123.7, 122.5 (q, J = 275.0 Hz), 120.6, 115.6 (d, J = 21.5 Hz), 115.1, 27.1 ppm; 19 F NMR (377 MHz, CDCl3) δ -64.42, -114.10 ppm; HRMS (ESI) m / z calcd for [C 19 H 13 NOF4 + H] + : 348.1006, found: 348.1027.

[0059] Methyl 4-(1-acetyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-3-yl)benzoate (3g): The regioselectivity ratio is 7:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 66%, 76.3 mg, m.p. 112 - 114 °C. 1 H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 8.4 Hz), 8.09 - 8.07 (m, 1H), 7.51 - 7.45 (m, 4H), 7.35 - 7.31 (m, 1H), 6.10 (q, J = 1.3 Hz, 1H), 5.69 (q, J = 1.0 Hz, 1H), 3.98 (s, 3H), 2.77 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 169.7, 166.9, 137.0, 135.8, 132.10 (q, J = 33.0 Hz), 130.2, 129.7, 129.5, 129.2, 127.9, 126.9 (q, J = 4.0 Hz), 126.4, 126.2, 123.8, 122.4 (q, J = 274.9 Hz), 120.5, 115.2, 52.2, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -65.97 ppm; HRMS (ESI) m / z calcd for 21 C 16 H + NO3F3 + H]

[0060] 1-(4-(1-Acetyl-2-(3,3,3-trifluoro-1-en-2-yl)-1H-indol-3-yl)phenyl)ethan-1-one (3h): The regioselectivity ratio was 3:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 62%, 69.3 mg. 1 1H NMR (400 MHz, CDCl3) δ 8.39 (dt, J = 8.4, 0.9 Hz, 0.3H), 8.09 - 8.06 (m, 4.1H), 7.57 - 7.43 (m, 5.9H), 7.40 - 7.31 (m, 1.5H), 6.13 - 6.12 (m, 0.3H), 6.11 (d, J = 1.3 Hz, 1H), 5.70 (d, J = 1.0 Hz, 1H), 5.53 (d, J = 1.3 Hz, 0.3H), 2.77 (s, 3H), 2.69 (s, 1H), 2.68 (s, 3H), 2.07 (s, 1H); 13 13C NMR (101 MHz, CDCl3) δ 197.8, 169.8, 137.2, 136.3, 135.8, 132.1 (q, J = 33.0 Hz), 130.4, 128.5, 128.0, 126.9 (d, J = 3.9 Hz), 126.4, 126.1, 123.9, 122.45 (d, J = 275.0 Hz), 120.52, 120.0, 115.2, 27.2, 26.7 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.20, -65.92 ppm. HRMS (ESI) m / z calcd for 21 C 16 H +: 372.1206, found: 372.1212.

[0061] 1-(3-(4-Nitrophenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3i): The regioselectivity ratio is 3:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 53%, 59.0 mg, m.p. 136 - 138 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.3 (d, J = 8.8 Hz, 2H), 8.08 (dt, J = 8.5, 0.9 Hz, 1H), 7.61 (d, J = 8.8 Hz, 2H), 7.53 - 7.47 (m, 2H), 7.36 (ddd, J = 8.1, 7.1, 0.9 Hz, 1H), 6.16 (q, J = 1.3 Hz, 1H), 5.73 (q, J = 1.1 Hz, 1H), 2.80 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.7, 147.4, 139.3, 135.7, 131.9 (q, J = 33.2 Hz), 131.0, 128.8, 128.4, 127.2 (q, J = 4.1 Hz), 126.6, 124.9, 124.1, 123.8, 122.3 (q, J = 275.0 Hz), 120.2, 115.2, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.28 ppm; HRMS (ESI) m / z calcd for 19 C 13 H2N2O2F3 + H] + : 375.0951, found: 375.0978.

[0062] 4-(1-Acetyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-3-yl)benzonitrile (3j): The regioselectivity ratio is 2:1, petroleum ether / ethyl acetate = 20:1, yellow solid, 57.9 mg, yield 56%, m.p. 118 - 120 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.08 (dt, J = 8.6, 0.9 Hz, 1H), 7.77 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.3 Hz, 2H), 7.52 - 7.45 (m, 2H), 7.35 (ddd, J = 8.0, 7.2, 1.0 Hz, 1H), 6.14 (q, J = 1.3 Hz, 1H), 5.70 (q, J = 1.2 Hz, 1H), 2.78 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 169.7, 137.2, 135.7, 132.3, 132.0 (q, J = 33.2 Hz), 130.8, 128.8, 128.2, 127.1 (q, J = 4.1 Hz), 126.6, 125.2, 124.0, 122.3 (q, J = 274.9 Hz), 120.3, 118.7, 115.2, 111.6, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.30 ppm; HRMS (ESI) m / z calcd for 20 C 13 17H14N2OF3 + H] + : 355.1053, found: 355.1037.

[0063] 1-(3-(4-(Trifluoromethoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3k): The regioselectivity ratio is 5:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 77%, 94.6 mg, m.p. 51 - 53 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.11 (dt, J = 8.1, 1.0 Hz, 1H), 7.51 - 7.45 (m, 4H), 7.37 - 7.33 (m, 3H), 6.15 (q, J = 1.3 Hz, 1H), 5.72 (q, J = 1.0 Hz, 1H), 2.79 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.7, 148.9, 135.7, 132.1 (q, J = 33.2 Hz), 131.6, 130.7, 129.5, 127.9, 126.8 (q, J = 4.2 Hz), 126.4, 125.9, 123.8, 122.4 (q, J = 273.4 Hz), 120.9, 120.54, 120.54 (q, J = 257.4 Hz), 115.2, 27.1 ppm; 19 19F NMR (377 MHz, CDCl3) δ -57.74, -64.39 ppm; HRMS (ESI) m / z calcd for 20 C 13 20H15N2OF6 + H] + : 414.0923, found: 414.0949.

[0064] 1-(3-(4′-Propyl-[1,1′-biphenyl]-4-yl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (31): The regioselectivity ratio is 10:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 85%, 110.6 mg, m.p. 107 - 109 °C. 1 H NMR (400 MHz, CDCl3) δ 8.15 (dt, J = 8.6, 0.9 Hz, 1H), 7.76 (d, J = 8.4 Hz, 2H), 7.67 (d, J = 8.2 Hz, 3H), 7.63 (dd, J = 7.7, 1.1 Hz, 1H), 7.55 - 7.49 (m, 3H), 7.40 - 7.36 (m, 3H), 6.17 (q, J = 1.2 Hz, 1H), 5.78 (q, J = 1.1 Hz, 1H), 2.81 (s, 3H), 2.73 (t, J = 7.3 Hz, 2H), 1.83 - 1.74 (m, 2H), 1.07 (t, J = 7.3 Hz, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.9, 142.2, 140.5, 137.9, 135.9, 132.3 (q, J = 32.9 Hz), 130.7, 130.5, 129.8, 129.1, 127.7, 127.2, 127.0, 126.9, 126.8 (q, J = 4.1 Hz), 126.3, 123.7, 122.6 (q, J = 275.0 Hz), 121.0, 115.2, 37.8, 27.2, 24.6, 14.0 ppm; 19 F NMR (377 MHz, CDCl3) δ -64.24 ppm; HRMS (ESI) m / z calcd for 28 H 24 [C + H

[0065] 1-(3-(m-Tolyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3m): The regioselectivity ratio is 4:1, petroleum ether / ethyl acetate = 20:1, yellow liquid, yield 75%, 77.6 mg. 11H NMR (400 MHz, CDCl3) δ 8.11 (d, J = 8.4 Hz, 1H), 7.54 (dt, J = 7.8, 0.9 Hz, 1H), 7.48 (ddd, J = 8.5, 7.2, 1.4 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.35 - 7.31 (m, 1H), 7.26 - 7.22 (m, 3H), 6.11 (q, J = 1.3 Hz, 1H), 5.72 (q, J = 1.1 Hz, 1H), 2.78 (s, 3H), 2.45 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.8, 138.0, 135.8, 132.4 (q, J = 32.9 Hz), 131.9, 130.8, 129.9, 128.5, 128.3, 127.59, 127.57, 127.2, 126.5 (q, J = 4.4 Hz), 126.1, 123.6, 122.5 (q, J = 275.2 Hz), 120.9, 115.1, 27.1, 21.4 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.24 ppm. HRMS (ESI) m / z calcd for 20 C 16 11H + NOF3 + H]

[0066] 1-(3-(Naphthalen-1-yl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3n): The regioselectivity ratio was 10:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 79%, 90.3 mg, m.p. 112 - 114 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J = 8.5 Hz, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.5 Hz, 1H), 7.60 (dd, J = 8.3, 7.0 Hz, 1H), 7.55 (ddd, J = 8.1, 6.8, 1.3 Hz, 1H), 7.50 - 7.47 (m, 2H), 7.43 (ddd, J = 8.2, 6.8, 1.3 Hz, 1H), 7.24 (ddd, J = 7.9, 7.1, 0.9 Hz, 1H), 7.13 (d, J = 7.9 Hz, 1H), 5.91 (s, 1H), 5.66 (s, 1H), 2.85 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 169.9, 135.8, 133.6, 133.2, 132.3 (q, J = 32.8 Hz), 130.7, 129.7, 129.2, 128.9, 128.8, 128.4, 126.32, 126.29, 126.2, 126.1 (2C), 125.8 (q, J = 6.4 Hz), 125.4, 123.8, 122.6 (q, J = 275.2 Hz), 121.4, 115.3, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -63.98 ppm, HRMS (ESI) m / z calcd for 23 C 16 H + NOF3 + H]

[0067] 1-(3-(Naphthalen-2-yl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3o): regioselectivity ratio 4:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 69%, 77.9 mg, m.p. 112 - 114 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.17 (dt, J = 8.4, 0.8 Hz, 1H), 8.00 - 7.92 (m, 4H), 7.62 - 7.57 (m, 4H), 7.52 (ddd, J = 8.5, 7.2, 1.3 Hz, 1H), 7.37 (ddd, J = 8.0, 7.2, 0.9 Hz, 1H), 6.11 (q, J = 1.3 Hz, 1H), 5.76 (q, J = 1.0 Hz, 1H), 2.83 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.9, 135.9, 133.4, 132.8, 132.3 (q, J = 32.9 Hz), 130.0, 129.6, 129.4, 128.2, 128.1, 128.00, 127.96, 127.8, 127.4, 126.8 (q, J = 4.2 Hz), 126.43, 126.42, 126.3, 123.8, 122.7 (q, J = 275.0 Hz), 121.0, 115.2, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.09 ppm; HRMS (ESI) m / z calcd for 23 C 16 H +: 380.1257, found: 380.1283.

[0068] 1-(3-(Thiophen-2-yl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3p): The regioselectivity ratio is 3:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 55%, 54.7 mg, m.p. 108 - 110 °C. 1 H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 7.7 Hz, 1H), 7.48 - 7.43 (m, 2H), 7.37 (dd, J = 3.0, 1.3 Hz, 1H), 7.36 - 7.32 (m, 1H), 7.21 (dd, J = 5.0, 1.3 Hz, 1H), 6.16 (d, J = 1.3 Hz, 1H), 5.74 (d, J = 1.1 Hz, 1H), 2.75 (s, 3H); 13 C NMR (126 MHz, CDCl3) δ 169.71, 132.32 (q, J = 32.9 Hz), 135.79, 131.71, 129.54, 128.79, 127.58, 126.49 (q, J = 4.1 Hz), 126.19, 125.62, 124.45, 123.68, 122.47 (q, J = 275.1 Hz), 122.36, 120.82, 115.11, 29.72 ppm. 19 F NMR (376 MHz, CDCl3) δ -64.38 ppm. HRMS (ESI) m / z calcd for [C 17 H 12 NOF3S+Na] + : 358.0484, found: 358.0465.

[0069] 1-(3-((5-Methoxy-1H-indol-1-yl)methyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3q): The regioselectivity ratio is 5:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 81%, 100 mg, m.p. 124 - 126 °C. 11H NMR (400 MHz, CDCl3) δ 8.03 (dd, J = 8.6, 0.9 Hz, 1H), 7.41 (ddd, J = 8.5, 4.8, 3.7 Hz, 1H), 7.35 (d, J = 8.9 Hz, 1H), 7.22 - 7.17 (m, 2H), 7.15 (d, J = 2.5 Hz, 1H), 6.97 - 6.91 (m, 2H), 6.43 (dd, J = 3.1, 0.8 Hz, 1H), 6.28 (d, J = 1.3 Hz, 1H), 5.67 (d, J = 1.1 Hz, 1H), 5.32 (s, 2H), 3.90 (s, 3H), 2.76 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.4, 154.2, 135.9, 131.9 (q, J = 30.8 Hz), 131.7, 129.7, 129.1, 128.5, 127.5, 126.3, 126.3 (q, J = 4.3 Hz), 125.1 (q, J = 274.6 Hz) 123.9, 120.1, 119.9, 115.2, 112.1, 110.0, 102.8, 101.6, 55.8, 40.3, 27.1 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.82 ppm; HRMS (ESI) m / z calcd for 23 C 19 H + N2O2F3 + H]

[0070] Example 4 investigated the applicability of the aniline substrate of formula (1).

[0071]

[0072] Using the aniline shown in formula (1) and 1-methoxy-4-(3-(trifluoromethyl)but-3-en-1-yn-1-yl)benzene (2a) as raw materials. Under the protection of argon, first add 10% mol Pd(OAc)2, 10% dppp ligand, 0.6 mmol K3PO4 and 0.6 mmol of the aniline shown in formula (1) to a dry Schlenk flask, then add 0.3 mmol of 1-methoxy-4-(3-(trifluoromethyl)but-3-en-1-yn-1-yl)benzene (2a) and 3 mL of DCE, place it in an oil bath and stir at 110 °C for 24 hours. After the reaction is completed, cool to room temperature, filter through diatomaceous earth, remove the solvent with a rotary evaporator, and purify the crude product by silica gel column chromatography. The eluent is petroleum ether / ethyl acetate to obtain the α-trifluoromethylvinyl indole compounds shown in formula (3), as shown in Table 3.

[0073] Table 3

[0074]

[0075] 1-(3-(4-methoxyphenyl)-5-methyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3r): regioselectivity ratio is 7:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 60%, 67.3 mg, m.p. 104 - 106 °C. 1 H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 8.7 Hz, 2H), 7.29 (d, J = 9.1 Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 6.10 (d, J = 1.3 Hz, 1H), 5.70 (s, 1H), 3.91 (s, 3H), 2.76 (s, 3H), 2.46 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.7, 159.2, 134.0, 133.3, 132.5 (q, J = 32.8 Hz), 131.3, 130.3, 127.6, 127.4, 127.00, 126.3 (q, J = 4.0 Hz), 124.2, 122.6 (q, J = 275.0 Hz), 120.6, 114.9, 113.9, 55.3, 27.0, 21.2 ppm; 19 F NMR (377 MHz, CDCl3) δ -64.34 ppm; HRMS (ESI) m / z calcd for 21 H 18 [C + HNOF3 + Na]

[0076] 1-(5-(dimethylamino)-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3s): regioselectivity ratio is 7:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 60%, 73.5 mg, m.p. 114 - 116 °C. 11H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 9.2 Hz, 1H), 7.35 (d, J = 8.7 Hz, 1H), 7.03 (d, J = 8.7 Hz, 1H), 6.98 (dd, J = 9.2, 2.7 Hz, 1H), 6.75 (d, J = 2.6 Hz, 1H), 6.07 (d, J = 1.4 Hz, 1H), 5.66 (d, J = 1.1 Hz, 1H), 3.90 (s, 3H), 2.96 (s, 6H), 2.73 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.3, 159.1, 148.1, 132.7 (q, J = 32.7 Hz), 131.3, 128.6, 127.9, 127.1, 126.0 (q, J = 4.0 Hz), 124.4, 122.6 (q, J = 275.1 Hz), 115.8, 113.9 (3C), 113.5, 103.2, 55.2, 41.5, 26.9 ppm; 19 19F NMR (377 MHz, CDCl3) δ -65.86 ppm; HRMS (ESI) m / z calcd for 22 C 21 11H12N2O2F3 + H] + : 403.1628, found: 403.1658.

[0077] 1-(5-(Benzyloxy)-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3t): The regioselectivity ratio was 5:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 57%, 79 mg, m.p. 114 - 116 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 9.1 Hz, 1H), 7.46 (d, J = 1.4 Hz, 2H), 7.45 - 7.41 (m, 2H), 7.39 - 7.36 (m, 1H), 7.34 - 7.31 (m, 2H), 7.16 (dd, J = 9.1, 2.6 Hz, 1H), 7.05 - 7.02 (m, 3H), 6.12 (d, J = 1.4 Hz, 1H), 5.72 (d, J = 1.1 Hz, 1H), 5.09 (s, 2H), 3.91 (s, 3H), 2.73 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 169.5, 159.2, 155.6, 137.0, 132.4 (q, J = 32.8 Hz), 131.2, 131.0, 130.7, 128.6, 128.0, 127.7, 127.0, 126.7, 126.6 (q, J = 3.4 Hz), 124.1, 122.6 (q, J = 275.0 Hz), 116.3, 115.5, 114.0, 104.5, 70.5, 55.3, 27.0 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.35 ppm; HRMS (ESI) m / z calcd for 27 C 22 H + N2O3F3 + H]

[0078] 1-(5-Fluoro-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3u): The regioselectivity ratio was 5:1, petroleum ether / ethyl acetate = 20:1, yellow solid, 64%, 72.6 mg, m.p. 96 - 98 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.12 (dd, J = 9.1, 4.4 Hz, 1H), 7.30 (d, J = 8.7 Hz, 2H), 7.18 - 7.11 (m, 2H), 7.01 (d, J = 8.7 Hz, 2H), 6.16 (q, J = 1.2 Hz, 1H), 5.76 (q, J = 1.1 Hz, 1H), 3.89 (s, 3H), 2.71 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.6, 159.6 (d, J = 241.3 Hz), 159.4, 132.3 (d, J = 1.0 Hz), 131.9 (q, J = 32.9 Hz), 131.1, 131.0 (d, J = 9.5 Hz), 128.6, 127.4 (q, J = 4.2 Hz), 126.9 (d, J = 4.0 Hz), 123.5, 122.4 (q, J = 275.1 Hz), 116.6 (d, J = 8.8 Hz), 114.1, 114.0 (d, J = 24.8 Hz), 106.1 (d, J = 24.1 Hz), 55.3, 27.0 ppm. 19 19F NMR (377 MHz, CDCl3) δ -64.50, -119.06 ppm. HRMS (ESI) m / z calcd for 20 C15 NO2F4 + H] + : 378.1112, found: 378.1130.

[0079] 1-(5-chloro-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3v): regioselectivity ratio is 5:1, petroleum ether / ethyl acetate = 20:1, dark green liquid, yield 50%, 59 mg. 1 HNMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.9 Hz, 1H), 7.44 (d, J = 2.1 Hz, 1H), 7.39 (dd, J = 8.9, 2.2 Hz, 1H), 7.29 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 6.16 (d, J = 1.4 Hz, 1H), 5.76 (s, 1H), 3.89 (s, 3H), 2.71 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.7, 159.5, 134.4, 131.9 (q, J = 34.6 Hz), 131.2, 129.4, 128.4, 127.44, 127.42 (q, J = 6.5 Hz), 126.6, 126.3, 123.4, 122.4 (q, J = 272.3 Hz), 120.3, 116.6, 114.1, 55.3, 27.0 ppm; 19 F NMR (377 MHz, CDCl3) δ -67.87 ppm. HRMS (ESI) m / z calcd for [C 20 H 15 NO2F3Cl + H] + : 393.0743 found: 393.0753.

[0080] 1-acetyl-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole-5-carbonitrile (3w): regioselectivity ratio is 4:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 55%, 64 mg, m.p. 112 - 114 °C. 11H NMR (400 MHz, CDCl3) δ 8.27 (dd, J = 8.7, 0.7 Hz, 1H), 7.79 (dd, J = 1.7, 0.7 Hz, 1H), 7.65 (dd, J = 8.8, 1.7 Hz, 1H), 7.28 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 8.7 Hz, 2H), 6.23 (d, J = 1.4 Hz, 1H), 5.84 (d, J = 1.1 Hz, 1H), 3.89 (s, 3H), 2.72 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.8, 159.6, 137.7, 131.10 (q, J = 33.1 Hz), 131.10, 129.8, 129.0, 128.9, 128.3 (q, J = 4.2 Hz), 126.8, 125.6, 122.6, 122.2 (q, J = 275.1 Hz), 119.2, 116.3, 114.3, 107.1, 55.3, 27.1 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.63 ppm; HRMS (ESI) m / z calcd for 21 C 15 11H12N2O2F3 + H] + : 385.1158, found: 385.1180.

[0081] 1-Acetyl-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole-5-carbaldehyde (3x): The regioselectivity ratio was 3:1, petroleum ether / ethyl acetate = 20:1, yellow solid, yield 18%, 21 mg, m.p. 116 - 118 °C. 1 1H NMR (400 MHz, CDCl3) δ 10.05 (s, 1H), 8.26 (d, J = 8.7 Hz, 1H), 8.00 (dd, J = 1.7, 0.7 Hz, 1H), 7.98 (dd, J = 8.7, 1.7 Hz, 1H), 7.32 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 6.19 (q, J = 1.3 Hz, 1H), 5.80 (q, J = 1.1 Hz, 1H), 3.90 (s, 3H), 2.75 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 191.7, 169.9, 159.5, 139.2, 132.4, 131.5 (d, J = 33.0 Hz), 131.2, 130.1, 128.7, 127.7 (q, J = 4.1 Hz), 127.6, 126.8, 124.0, 123.1, 122.3 (q, J = 275.2 Hz), 115.7, 114.2, 55.3, 27.2 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.56 ppm; HRMS (ESI) m / z calcd for 21 C 16 H + NO3F3 + H]

[0082] 1-(3-(4-Methoxyphenyl)-6-nitro-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3y): regioselectivity ratio 11:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 67%, 81.2 mg, m.p. 120 - 122 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.31 (dd, J = 2.0, 0.9 Hz, 1H), 8.29 - 8.23 (m, 2H), 7.30 (d, J = 8.7 Hz, 2H), 7.03 (d, J = 8.7 Hz, 2H), 6.26 (d, J = 1.3 Hz, 1H), 5.89 (d, J = 1.1 Hz, 1H), 3.90 (s, 3H), 2.74 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 169.9, 159.7, 144.2, 138.8, 131.1, 130.9 (q, J = 33.4 Hz), 129.63, 129.61, 128.6 (q, J = 4.1 Hz), 127.6, 122.4, 122.2 (q, J = 275.1 Hz), 121.1, 116.9, 115.8, 114.3, 55.3, 27.1 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.65 ppm; HRMS (ESI) m / z calcd for 20 C 15 H + N2O4F3 + H]

[0083] 1-(3-(4-Methoxyphenyl)-6-(trifluoromethyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3z): The regioselectivity ratio is 5:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 54%, 69.4 mg, m.p. 100 - 102 °C. 1 H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.59 - 7.51 (m, 2H), 7.30 (d, J = 8.7 Hz, 2H), 7.02 (d, J = 8.7 Hz, 2H), 6.21 (d, J = 1.3 Hz, 1H), 5.81 (d, J = 1.1 Hz, 1H), 3.90 (s, 3H), 2.74 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.8, 159.5, 135.2, 132.1, 131.5 (q, J = 33.0 Hz), 131.2, 129.4, 128.2 (q, J = 32.1 Hz), 127.9 (q, J = 3.5 Hz), 126.9, 124.6 (q, J = 272.2 Hz), 123.2, 122.3 (q, J = 275.1 Hz), 121.1, 120.4 (q, J = 3.5 Hz), 114.1, 113.0 (q, J = 4.4 Hz), 55.3, 27.1 ppm; 19 F NMR (377 MHz, CDCl3) δ -61.16, -64.59 ppm; HRMS (ESI) m / z calcdfor [C 21 H 15 NO2F6 + H] + : 428.1080, found: 428.1083.

[0084] 1-(6-Fluoro-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethan-1-one (3aa): The regioselectivity ratio is 14:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 67%, 74 mg, m.p. 98 - 100 °C. 1 H NMR (400 MHz, CDCl3) δ 7.92 (dt, J = 10.6, 1.8 Hz, 1H), 7.42 - 7.38 (m, 1H), 7.30 (d, J = 8.7 Hz, 2H), 7.06 (tt, J = 8.9, 1.8 Hz, 1H), 7.00 (d, J = 8.7 Hz, 2H), 6.15 (s, 1H), 5.76 (s, 1H), 3.89 (s, 3H), 2.69 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 169.8, 161.9 (d, J = 242.5 Hz), 159.3, 136.2 (d, J = 12.5 Hz), 131.9 (q, J = 32.8 Hz), 131.1, 127.3 (q, J = 3.8 Hz), 127.1 (d, J = 1.1 Hz), 126.1 (d, J = 1.3 Hz), 123.7, 122.4 (d, J = 275.1 Hz), 121.5 (d, J = 10.0 Hz), 114.1, 114.0, 112.0 (d, J = 24.1 Hz), 103.0 (d, J = 29.1 Hz), 55.3, 27.0 ppm. 19 19F NMR (377 MHz, CDCl3) δ -65.98, -115.83 ppm; HRMS (ESI) m / z calcd for [C 20 H 15 NO2F4 + H] + : 378.1112, found: 378.1137.

[0085] Methyl 1-acetyl-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole-5-carboxylate (3ab): The regioselectivity ratio was 5:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 54%, 67.7 mg, m.p. 114 - 116 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 1.3 Hz, 1H), 8.00 (dd, J = 8.3, 1.3 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.31 (d, J = 8.7 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 6.13 (d, J = 1.4 Hz, 1H), 5.72 (s, 1H), 4.00 (s, 3H), 3.89 (s, 3H), 2.81 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 169.5, 167.3, 159.4, 135.1, 133.4, 132.0 (q, J = 33.1 Hz), 131.2, 130.3, 127.6, 126.9 (q, J = 4.2 Hz), 126.7, 124.6, 123.4, 122.3 (q, J = 275.0 Hz) 120.6, 116.8, 114.1, 55.3, 52.4, 27.2; 19 19F NMR (376 MHz, CDCl3) δ -64.25 ppm. HRMS (ESI) m / z calcd for [C22 H 18 NO2F3 + H] + :418.1261, found: 418.1269.

[0086] (3-(4-Methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)benzophenone (3ac): regioselectivity ratio is 9:1, petroleum ether / ethyl acetate = 10:1, yellow solid, yield 59%, 73.9 mg, m.p. 120 - 122 °C. 1 H NMR (400 MHz, CDCl3) δ 7.85 (dt, J = 8.1, 1.1 Hz, 2H), 7.69 (ddt, J = 7.9, 6.9, 1.3 Hz, 1H), 7.58 - 7.52 (m, 3H), 7.42 (d, J = 8.7 Hz, 2H), 7.24 (td, J = 7.4, 1.1 Hz, 1H), 7.18 (td, J = 7.8, 7.2, 1.4 Hz, 1H), 7.04 (d, J = 8.7 Hz, 2H), 6.95 (dd, J = 8.2, 1.0 Hz, 1H), 6.07 (q, J = 1.3 Hz, 1H), 5.72 (s, 1H), 3.91 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 169.6, 159.1, 136.6, 134.9, 133.4, 131.1, 130.21, 130.23 (q, J = 32.3 Hz), 129.4, 128.8, 128.5, 127.6 (q, J = 5.3 Hz), 126.3, 125.0, 124.3, 122.9, 122.5 (q, J = 274.4 Hz), 120.7, 114.01, 113.98, 55.3 ppm; 19 F NMR (377 MHz, CDCl3) δ -64.83 ppm; HRMS (ESI) m / z calcd for [C 25 H 18 NO2F3 + H] + :422.1362, found: 422.1390.

[0087] 1-Benzyl-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole (3ad): regioselectivity ratio is >20:1, petroleum ether / ethyl acetate = 10:1, yellow liquid, yield 69%, 84.0 mg. 11H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 8.7 Hz, 2H), 7.38 - 7.28 (m, 5H), 7.25 - 7.19 (m, 1H), 7.07 (d, J = 7.2 Hz, 2H), 7.04 (d, J = 8.7 Hz, 2H), 6.33 (d, J = 1.5 Hz, 1H), 5.74 (d, J = 1.4 Hz, 1H), 5.42 (s, 2H), 3.91 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 158.35, 137.75, 136.88, 130.85, 130.72 (q, J = 33.0 Hz), 130.14 (q, J = 4.5 Hz), 128.73, 128.39, 127.36, 127.35, 126.56, 126.00, 123.23, 122.49 (d, J = 274.8 Hz), 120.42, 120.26, 118.74, 113.82, 110.60, 55.26, 47.78 ppm; 19 19F NMR (376 MHz, CDCl3) δ -65.28 ppm. HRMS (ESI) m / z calcd for 25 C 20 H + NOF3 + H]

[0088] 3-(4-Methoxyphenyl)-1-phenyl-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole (3ae): The regioselectivity ratio was >20:1, petroleum ether / ethyl acetate = 10:1, yellow liquid, yield 53%, 67.5 mg. 1 1H NMR (400 MHz, CDCl3) δ 7.75 (dt, J = 7.7, 1.1 Hz, 1H), 7.56 (dd, J = 8.4, 6.6 Hz, 2H), 7.51 - 7.47 (m, 3H), 7.41 (dd, J = 7.3, 1.8 Hz, 2H), 7.31 - 7.23 (m, 3H), 7.06 - 7.04 (m, 2H), 6.20 (d, J = 1.5 Hz, 1H), 5.77 (d, J = 1.4 Hz, 1H), 3.93 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 158.5, 138.1, 137.7, 131.0, 130.9 (d, J = 33.4 Hz), 129.80 (d, J = 4.7 Hz), 129.2, 128.8, 128.5, 128.0, 127.1, 126.4, 125.6 (d, J = 281.6 Hz), 123.6, 120.9, 120.1, 119.9, 113.9, 110.8, 55.3 ppm. 19 19F NMR (377 MHz, CDCl3) δ -64.68 ppm. HRMS (ESI) m / z calcd for 24 C 19 H + NOF3 + H]

[0089] 1-(3-(4-Methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)-2,2-dimethylpropan-1-one (3af): regioselectivity ratio is 5:1, petroleum ether / ethyl acetate = 10:1, yellow liquid, yield 83%, 100 mg. 1 1H NMR (400 MHz, CDCl3) δ 7.57 - 7.53 (m, 2H), 7.36 (d, J = 8.8 Hz, 2H), 7.24 (dd, J = 8.3, 7.1 Hz, 1H), 7.01 (d, J = 8.6 Hz, 2H), 6.21 (d, J = 1.4 Hz, 1H), 5.83 (d, J = 1.4 Hz, 1H), 3.89 (s, 3H), 1.46 (s, 9H); 13 13C NMR (101 MHz, CDCl3) δ 184.32, 158.92, 135.63, 131.14, 130.85 (d, J = 32.7 Hz), 128.72 (q, J = 4.6 Hz), 128.38, 127.78, 125.03, 124.62, 123.79, 122.39 (d, J = 274.9 Hz), 121.87, 120.68, 113.90, 112.75, 55.26, 43.62, 27.98 ppm; 19 19F NMR (377 MHz, CDCl3) δ -64.21 ppm; HRMS (ESI) m / z calcd for C 23 H 22 F3NO2 [M + H] + : 402.1675, found 402.1675.

[0090] Example 5 Photochromic Performance Test

[0091] 0.3 mmol of compound 3a and 0.3 mmol of compound 4a were separately placed in different reaction flasks, and 5 mL of tetrahydrofuran (THF) and dilute sodium hydroxide aqueous solution were added respectively. The deacetylation reaction occurred under stirring at room temperature, and compounds 8 and 11 were separated.

[0092] 3-(4-Methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole (8): 1 H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.47 - 7.44 (m, 3H), 7.34 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.22 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 7.06 (d, J = 8.8 Hz, 2H), 6.02 (q, J = 1.5 Hz, 1H), 5.65 (q, J = 1.6 Hz, 1H), 3.93 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 158.6, 135.6, 131.1, 129.5 (q, J = 31.0 Hz), 127.9, 126.5, 125.8, 124.7 (q, J = 5.6 Hz), 123.8, 123.2 (q, J = 274.0 Hz), 120.6, 120.1, 119.1, 114.3, 111.2, 55.3 ppm. 19 F NMR (377 MHz, CDCl3) δ -65.45 ppm. HRMS (ESI) m / z calcd for 18 H 14 F3NO + H] + : 318.1100, found: 318.1102.

[0093] 2-(4-Methoxyphenyl)-3-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indole (11): 1 H NMR (400 MHz, Chloroform-d) δ 8.28 (s, 1H), 7.67 - 7.60 (m, 1H), 7.58 - 7.51 (m, 2H), 7.41 (dt, J = 8.0, 1.0 Hz, 1H), 5.70 - 5.61 (m, 1H), 7.32 - 7.18 (m, 3H), 7.01 (d, J = 8.9 Hz, 1H), 6.27 - 6.16 (m, 1H), 5.67 - 5.64 (m, 1H), 3.89 (s, 3H) ppm

[0094] Compound 8 was dissolved in a mixed solvent of petroleum ether / ethyl acetate, and the solution was colorless; it was excited with light at 365 nm for 30 seconds, and the color of the solution changed from colorless to red. After removing the light irradiation, the color of the solution gradually faded from red and became a colorless solution after 5 minutes. Therefore, compound 3a has photochromic properties and can be used as a photochromic material, including in high-intensity light dose meters, information storage elements, anti-counterfeiting, decorative, and protective packaging materials.

[0095] Compound 11 was dissolved in chloroform and irradiated with light (365 nm) under air. The color of the solution changed from colorless to yellow, but after removing the light irradiation, the color of the solution could not return to colorless. After photoexcitation for 12 hours, compound 11 was converted to benzocarbazole compound 12 with a yield of 70%. Therefore, compound 4a does not have photochromic properties and only exhibits a photoinduced electrocyclization-oxidative aromatization reaction.

[0096] 3-Methoxy-6-trifluoromethyl-11H-benzo[a]carbazole (12): 1 H NMR (400 MHz, Chloroform-d) δ 8.93 (s, 1H), 8.33 (d, J = 8.2 Hz, 1H), 8.10 (d, J = 8.9 Hz, 1H), 7.94 (s, 1H), 7.62 (dt, J = 8.1, 0.9 Hz, 1H), 7.49 (ddd, J = 8.2, 7.1, 1.1 Hz, 1H), 7.44 - 7.38 (m, 2H), 7.38 - 7.34 (m, 1H), 4.01 (s, 3H) ppm.

[0097] In addition, it was also found in this example that the α-trifluoromethylvinyl indole compounds shown in formula (3) also all exhibit photochromic properties. Therefore, the α-trifluoromethylvinyl indole compounds shown in formula (3) can be used as photochromic materials and applied in high-intensity light dose meters, information storage elements, anti-counterfeiting, decorative, and protective packaging materials.

[0098] Example 6 Derivatization Experiment

[0099] To further confirm the practical application value of this method, a gram-scale reaction of N-(2-iodophenyl)acetamide (1a) and 1-methoxy-4-(3-(trifluoromethyl)but-3-en-1-yn-1-yl)benzene (2a) was carried out under the optimized standard conditions of Example 1, and 1.73 g of the product 1-(3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-1-yl)ethanone (3a) with a 5:1 regioselectivity was obtained in an overall yield of 85%. Subsequently, a series of derivatization studies were carried out on compound 3a, such as Figure 7As shown, the traditional hydroboration-oxidation reaction follows the anti-Markovnikov rule for alkenes. Surprisingly, when 3a undergoes hydroboration-oxidation, the Markovnikov addition tertiary alcohol compound 6 with a trifluoromethyl quaternary carbon center is anomalously obtained in 70% yield. This discovery is of great significance, showing a complementary selectivity pattern to the traditional alkene hydroboration-oxidation reaction.

[0100] Drawing on the work of the Jiao group on oxidative bromination reaction (HBr / DMSO system) ((a) Song, S.; Sun, X.; Li, X.; Yuan, Y.; Jiao, N. Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization. Org. Lett. 2015, 17, 2886 - 2889; (b) Song, S.; Huang, X.; Liang, Y.-F.; Tang, C.; Li, X.; Jiao, N. From simple organobromides or olefins to highly value-added bromohydrins: a versatile performance of dimethyl sulfoxide. Green Chem. 2015, 17, 2727 - 2731), when 3a is in this system, no hydroxybromination, dibromination or aromatic ring bromination reactions occur. Instead, without the need for a metal catalyst, radical initiator or light, the anti-Markovnikov hydrobromination product primary alkyl bromide compound 7 is obtained in 50% yield. These results suggest that the fluorine effect of the CF3 group may play a key role in these two reactions. In the acetyl deprotection reaction, the indole derivative compound 8 is successfully obtained in 52% yield through the sodium hydride / acetanilide system, and the sodium hydroxide system has a higher deprotection efficiency (98% yield). Using the acetyl group as a directing group, the carbonyl-directed C-H alkenylation reaction at the C7 position of indole is smoothly achieved, and the diene product compound 9 is obtained in 65% yield. In addition, after deprotection of 3a with sodium hydroxide, compound 10 is obtained in 57% yield through palladium-catalyzed Heck coupling reaction.

[0101] 1-(3-(4-Methoxyphenyl)-2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1H-indol-1-yl)ethan-1-one (6): white solid; yield 70%, 70.0 mg; 11H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 7.44 (d, J = 8.2 Hz, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.34 - 7.28 (m, 2H), δ 7.13 (t, J = 7.3 Hz, 1H), 7.03 (d, J = 8.6 Hz, 2H), 3.92 (s, 3H), 3.00 (s, 1H), 1.66 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 159.0, 134.4, 132.2, 129.7, 129.6, 126.3, 125.2 (q, J = 286.0 Hz), 123.3, 120.1, 120.0, 116.8, 113.8, 110.9, 73.7 (q, J = 30.7 Hz), 55.3, 23.0 ppm; 19 19F NMR (377 MHz, CDCl3) δ -81.00 ppm; HRMS (ESI) m / z calcd for 18 C 18 H + F3NO2 + H]

[0102] 2-(3-Bromo-1,1,1-trifluoropropan-2-yl)-3-(4-methoxyphenyl)-1H-indole (7): white solid; yield 50%, 40.0 mg; 1 1H NMR (400 MHz, CDCl3) δ 8.38 (s, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.52 - 7.49 (m, 3H), 7.37 (ddd, J = 8.3, 7.1, 1.2 Hz, 1H), 7.24 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H), 7.13 (d, J = 8.7 Hz, 2H), 4.30 (pd, v = 8.9, 4.7 Hz, 1H), 3.97 (s, 3H), 3.88 (dd, J = 10.8, 4.6 Hz, 1H), 3.76 (dd, J = 10.9, 9.2 Hz, 1H); 13 13C NMR (101 MHz, CDCl3) δ 159.0, 136.0, 131.4, 127.7, 125.9, 125.4 (q, J = 282.1 Hz), 124.8, 123.6, 120.7, 120.6, 120.1, 114.4, 111.3, 55.45 (q, J = 4.0 Hz), 43.9 (q, J = 29.6 Hz), 27.4 (q, J = 3.5 Hz) ppm; 1919F NMR (377 MHz, CDCl3) δ -67.31 ppm. HRMS (ESI) m / z calcd for [C 18 H 15 F3BrNO + H] + : 398.0362, found: 398.0370.

[0103] (E)-Methyl 3-(1-acetyl-3-(4-methoxyphenyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)-1H-indol-7-yl)acrylate (9): 1 1H NMR (400 MHz, CDCl3) δ 7.92 (d, J = 15.9 Hz, 1H), 7.59 (d, J = 7.5 Hz, 1H), 7.55 (d, J = 8.1 Hz, 1H), 7.36 - 7.32 (m, 3H), 7.01 (d, J = 8.7 Hz, 2H), 6.52 (d, J = 15.8 Hz, 1H), 6.21 (q, J = 1.3 Hz, 1H), 5.80 (q, J = 1.3 Hz, 1H), 3.89 (s, 3H), 3.87 (s, 3H), 2.54 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 171.3, 167.1, 159.3, 142.6, 134.6, 131.5, 131.1, 128.8, 128.5 (q, J = 4.3 Hz), 125.3, 125.2, 124.0, 123.9, 122.71, 122.67, 122.5 (q, J = 275.4 Hz), 118.5, 114.1 (3C), 55.32 (q, J = 4.1 Hz), 51.9 (q, J = 3.9 Hz), 27.5 ppm. 19 19F NMR (377 MHz, CDCl3) δ -64.43 ppm. HRMS (ESI) m / z calcd for [C 24 H 20 F3NO4 + H] + : 444.1417, found: 444.1418.

[0104] (Z)-3-(4-Methoxyphenyl)-2-(3,3,3-trifluoro-1-(naphthalen-1-yl)prop-1-en-2-yl)-1H-indole (10): 11H NMR (500 MHz, CDCl3) δ 8.41 (s, 1H), 7.83 (s, 1H), 7.71 (d, J = 7.9 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.42 - 7.38 (m, 2H), 7.33 - 7.26 (m, 3H), 7.09 (d, J = 7.7 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.91 (d, J = 7.2 Hz, 1H), 6.62 (d, J = 8.7 Hz, 2H), 6.28 (d, J = 8.7 Hz, 2H), 3.54 (s, 3H); 13 13C NMR (126 MHz, CDCl3) δ 157.54, 136.19, 136.15 (q, J = 5.5 Hz), 133.12, 131.09, 131.00, 129.41, 129.09, 127.93, 127.40, 126.24, 125.83, 125.63, 125.01, 124.69, 123.98 (d, J = 273.9 Hz), 123.54, 123.28, 122.86 (d, J = 29.9 Hz), 120.17, 119.89, 119.85, 114.51, 113.29, 111.11, 54.75 ppm. 19 19F NMR (376 MHz, CDCl3) δ -64.43 ppm. HRMS (ESI) m / z calcd for 28 C 20 H + NOF3 + H]

[0105] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific embodiments described. Obviously, many modifications and variations can be made according to the content of this specification. These embodiments are selected and specifically described in this specification to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and utilize the present invention well. The present invention is only limited by the claims and their full scope and equivalents.

Claims

1. A method for preparing α-trifluoromethyl vinyl indole compounds, characterized in that, The reaction formula is as shown in (I), including the following steps: Under the protection of an inert gas, to the aniline mixed with a palladium catalyst, a ligand, a base and the aniline shown in formula (1), add the β-CF3-1,3-enyne shown in formula (2) and 1,2-dichloroethane, stir and react at 80-110 °C for 12-24 h, and obtain the α-trifluoromethylvinyl indole compound shown in formula (3) through separation and purification; Wherein, X is I or Br; R1 is hydrogen, alkyl, alkoxy, haloalkyl, benzyloxy, halogen, cyano, nitro, alkanoyl, alkanamino or ester group; R2 is acetyl, benzoyl, benzyl, phenyl or tert-butylformyl; R3 is phenyl, substituted phenyl, naphthyl or aromatic heterocyclic group, wherein the substituent in the substituted phenyl is hydrogen, alkyl, alkoxy, halogen, cyano, nitro, alkanoyl or ester group.

2. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 1, characterized in that, It also includes filtering, concentrating under reduced pressure after the reaction, and then separating by column chromatography to obtain the α-trifluoromethylvinyl indole compound shown in formula (3), wherein the eluent is petroleum ether / ethyl acetate = 10-50:

1.

3. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 1, characterized in that, The palladium catalyst is palladium acetate, palladium trifluoroacetate, tetrakis(triphenylphosphine)palladium or dichloro(dinitrile)palladium.

4. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 1, characterized in that, The base is sodium carbonate, cesium carbonate, potassium carbonate, potassium acetate, potassium phosphate, N,N-diisopropylethylamine or triethylamine.

5. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 4, wherein, The base is potassium phosphate.

6. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 1, wherein The ligand is a phosphine ligand or a N-heterocyclic carbene ligand. Among them, the phosphine ligand is BINAP, dppf, Xantphos, dppe, dppp, Cy3P, t-Bu3P, t-BuXPhos or t-BuPHBF4, and the N-heterocyclic carbene ligand is SIPrHCl.

7. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 6, characterized in that, The ligand is BINAP or dppp.

8. The preparation method of the α-trifluoromethyl vinyl indole compound according to claim 1, characterized in that, The feeding ratio of the aniline shown in formula (1), the β-CF3-1,3-enyne shown in formula (2), the palladium catalyst, the base and the ligand is 1.1-2.5:1:0.05-0.2:1-2:0.05-0.

2.

9. An α-trifluoromethylvinyl indole compound prepared by the preparation method according to any one of claims 1-8.

10. Use of the α-trifluoromethylvinyl indole compound according to claim 9 in a photochromic material.

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