An e-type beta-trifluoromethyl enamide compound and an electrochemical oxidation synthesis method thereof

Abstract

The application provides an E-type beta-trifluoromethyl enamide compound, which has a structure shown in formula (I), an electrochemical oxidation synthesis method, which comprises the following steps: stirring and mixing non-cyclic enamide compounds, trifluoromethyl sulfinic acid salts, additives and solvents in a reactor equipped with electrode sheets, and performing beta-C(sp 2 )-H trifluoromethylation reaction under electrochemical conditions, so that a series of E-type beta-trifluoromethyl enamide compounds are obtained with high selectivity. The application uses electric current as an oxidant, does not need to add electrolytes, and does not need to add various metal catalysts and chemical oxidants. The reaction condition is mild, the substrate universality is wide, and the functional group tolerance is good. The application is simple and easy to implement, the reaction system is simple, and the pollution is small, which meets the green chemistry concept and has good application potential.

Description

TECHNICAL FIELD

[0001] One or more embodiments of the present specification relate to the technical field of electrochemical organic synthesis, and in particular, to an E-type β-trifluoromethyl enamide compound and an electrochemical oxidation synthesis method thereof. BACKGROUND

[0002] As an important fluorine-containing functional group, the trifluoromethyl functional group has many unique properties, such as strong electron-withdrawing property, good metabolic stability, and better fat solubility. Many medicines, agricultural chemicals, dyes, and many functional materials contain trifluoromethyl functional groups. Therefore, introducing a trifluoromethyl functional group into a compound has always attracted widespread attention from chemists. On the other hand, enamide compounds, as an important synthetic building block in organic synthesis, are widely used in the synthesis of many chiral amines and nitrogen-containing heterocyclic compounds. The direct functionalization of β-C(sp 2 )-H of enamide is an effective strategy to construct functionalized enamide compounds, and thus, a series of important research results have been achieved. However, there are relatively few reports on the synthesis of β-trifluoromethyl enamide compounds. In 2012, Loh's group reported the first example of copper-catalyzed trifluoromethylation of β-C(sp 2 )-H of enamide (C. Feng and T.-P. Loh, Chem. Sci., 2012, 3, 3458.), which has good stereoselectivity, but the reaction needs to use expensive Togni's reagent as a trifluoromethyl source, and the copper catalyst used in this method is toxic and complex to prepare. In 2021, Yang's group reported a case of photocatalytic trifluoromethylation of β-C(sp 2 )-H of enamide (K. Tang, Y. Chen, J. Guan, Z. Wang, K. Chen, H. Xiang and H. Yang, Org. Biomol. Chem., 2021, 19, 7475.), which avoids the use of toxic chemicals to some extent, but the reaction needs to use expensive iridium catalyst as photosensitizer, and the reaction has poor stereoselectivity. In view of the above, the present application proposes an E-type β-trifluoromethyl enamide compound and an electrochemical oxidation synthesis method thereof to solve the above problems. SUMMARY

[0003] Therefore, one or more embodiments of the present specification aim to propose an E-type β-trifluoromethyl enamide compound and an electrochemical oxidation synthesis method thereof to solve the problems proposed in the background.

[0004] In order to achieve the above purpose, one or more embodiments of the present specification provide an E-type β-trifluoromethyl enamide compound, which has the structure shown in formula (I):

[0005]

[0006] wherein R 1 is hydrogen, alkyl, alkoxy, halogen, hydroxyl, aryl, acyl or ester, etc.; R 2 is benzyl, substituted benzyl, methyl, acyl or tert-butyloxycarbonyl.

[0007] Preferably, the E-type β-trifluoromethyl enamide compound includes:

[0008]

[0009] An electrochemical oxidation synthesis method for synthesizing the E-type β-trifluoromethyl enamide compound described above includes the following steps:

[0010] In a reactor equipped with an electrode sheet, a non-cyclic enamide compound, a trifluoromethyl sulfinic acid salt, an additive and a solvent are stirred and mixed, and under electrochemical conditions, a β-C(sp 2 )-H trifluoromethylation reaction is carried out to obtain a series of E-type β-trifluoromethyl enamide compounds with high selectivity.

[0011] More preferably, the non-cyclic enamide compound has a structure shown in formula (II):

[0012]

[0013] More preferably, the trifluoromethyl sulfinic acid salt has a structure shown in formula (III):

[0014] CF3SO2M

[0015] Formula (III);

[0016] wherein M is a metal cation.

[0017] More preferably, the additive is selected from any one or a mixture of several of formic acid, acetic acid, sulfuric acid, hydrochloric acid, trifluoroacetic acid and phosphoric acid.

[0018] More preferably, the solvent is selected from any one or a mixture of several of dimethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, methanol, ethanol, tetrahydrofuran and dichloromethane.

[0019] More preferably, the molar ratio of the non-cyclic enamide compound, the trifluoromethyl sulfinic acid salt and the additive is 1.0:(1.0-5.0):(0.5-3.0); and the starting concentration of the non-cyclic enamide compound is 0.02-0.1 mol / L.

[0020] More preferably, the reactor used in the electrochemical conditions is a non-separated electrolytic cell, the power supply is a direct current stabilized power supply, the reaction is carried out under constant current conditions, and the current is 5-15 mA.

[0021] More preferably, the trifluoromethylation reaction temperature is 0-60 DEG C, and the reaction time is 2-10 h.

[0022] More preferably, the trifluoromethylation reaction further comprises separation and purification, and the separation and purification mode is selected from any one or more of column chromatography, liquid chromatography, distillation and recrystallization.

[0023] From the above, it can be seen that the present application includes the following beneficial effects:

[0024] From the above, it can be seen that the present application has the beneficial effect of providing a method for electrochemically oxidizing and synthesizing E-type beta-trifluoromethyl enamide compounds. Under electrochemical conditions, beta-C (sp2) -H trifluoromethylation reaction is carried out to obtain a series of E-type beta-trifluoromethyl enamide compounds with high selectivity. The present application uses current as an oxidant, without the need for additional electrolyte, and without the need for adding various metal catalysts and chemical oxidants; the reaction conditions are mild, the substrate universality is wide, and the functional group tolerance is good; the present application is simple and easy to operate, the reaction system is simple, the pollution is small, and it meets the green chemistry concept, and has good application potential. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical solutions in the one or more embodiments of the present application or the prior art, the drawings needed in the embodiment or prior art description will be briefly introduced below. Obviously, the drawings in the following description are only one or more embodiments of the present application, and other drawings can also be obtained by those skilled in the art without creative labor.

[0026] Figures 1-3 The nuclear magnetic hydrogen spectrum, carbon spectrum and fluorine spectrum of the product prepared in Example 1 in the present application are shown in the following figures:

[0027] Figures 4-6 The nuclear magnetic hydrogen spectrum, carbon spectrum and fluorine spectrum of the product prepared in Example 2 in the present application are shown in the following figures:

[0028] Figures 7-9 The nuclear magnetic hydrogen spectrum, carbon spectrum and fluorine spectrum of the product prepared in Example 3 in the present application are shown in the following figures:

[0029] Figures 10-12 The nuclear magnetic hydrogen spectrum, carbon spectrum and fluorine spectrum of the product prepared in Example 4 in the present application are shown in the following figures:

[0030] Figures 13-15 The nuclear magnetic hydrogen spectrum, carbon spectrum and fluorine spectrum of the product prepared in Example 5 in the present application are shown in the following figures:

[0031] Figures 16-18 NMR spectra of hydrogen, carbon and fluorine of the product prepared in Example 6 in the present application;

[0032] Figures 19-21 NMR spectra of hydrogen, carbon and fluorine of the product prepared in Example 7 in the present application;

[0033] Figures 22-24 NMR spectra of hydrogen, carbon and fluorine of the product prepared in Example 8 in the present application;

[0034] Figures 25-27 NMR spectra of hydrogen, carbon and fluorine of the product prepared in Example 9 in the present application;

[0035] Figures 28-30 NMR spectra of hydrogen, carbon and fluorine of the product prepared in Example 10 in the present application. DETAILED DESCRIPTION

[0036] In order to make the purpose, technical scheme and advantages of the present disclosure more clear, the present disclosure is further described in detail below in combination with specific embodiments.

[0037] One or more embodiments of the present specification provide an E-type β-trifluoromethyl enamide compound having a structure shown in formula (I):

[0038]

[0039] wherein, R 1 is hydrogen, alkyl, alkoxy, halogen, hydroxyl, aryl, acyl or ester group, etc.; R 2 is benzyl, substituted benzyl, methyl, acyl or tert-butoxycarbonyl.

[0040] As an improved scheme of the above scheme, the E-type β-trifluoromethyl enamide compound comprises:

[0041]

[0042] The electrochemical oxidation synthesis method proposed in the embodiments of the present application is used for synthesizing the E-type β-trifluoromethyl enamide compound described above, and comprises the following steps:

[0043] In a reactor equipped with an electrode sheet, a non-cyclic enamide compound, a trifluoromethyl sulfinic acid salt, an additive and a solvent are stirred and mixed, and under an electrochemical condition, a β-C(sp 2 )-H trifluoromethylation reaction is carried out, and a series of E-type β-trifluoromethyl enamide compounds are obtained with high selectivity.

[0044] As an improved scheme of the above scheme, the non-cyclic enamide compound has a structure shown in formula (II):

[0045]

[0046] As an improved scheme of the above scheme, the trifluoromethyl sulfinate salt has a structure shown in formula (III):

[0047] CF3SO2M

[0048] Formula (III);

[0049] Wherein, M is a metal cation.

[0050] As an improved scheme of the above scheme, the additive is selected from any one or mixture of several of formic acid, acetic acid, sulfuric acid, hydrochloric acid, trifluoroacetic acid and phosphoric acid.

[0051] As an improved scheme of the above scheme, the solvent is selected from any one or mixture of several of dimethyl sulfoxide, N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, methanol, ethanol, tetrahydrofuran and dichloromethane.

[0052] As an improved scheme of the above scheme, the molar ratio of the non-cyclic enamide compound, the trifluoromethyl sulfinate salt and the additive is 1.0: (1.0-5.0): (0.5-3.0); the starting concentration of the non-cyclic enamide compound is 0.02-0.1 mol / L, and is further preferably 0.04-0.08 mol / L.

[0053] As an improved scheme of the above scheme, the reactor used in the electrochemical condition is a non-separated electrolytic cell, the power supply is a direct current stabilized power supply, the reaction is carried out under constant current condition, the current is 5-15 mA, and is further preferably 8-12 mA.

[0054] As an improved scheme of the above scheme, the trifluoromethylation reaction temperature is 0-60℃; and is further preferably 20-40℃; the reaction time is 2-10 h, and is further preferably 4-8 h.

[0055] In the present application, the preparation process of the E-type β-trifluoromethyl enamide compound is as follows:

[0056]

[0057] In the present application, the electrode is not particularly limited, and can be a platinum electrode, a carbon electrode, a nickel electrode, an iron electrode, a copper electrode, a magnesium electrode and the like electrode known to those skilled in the art.

[0058] The mixing method is not particularly limited, and a mixing method known to those skilled in the art can be used.

[0059] The trifluoromethylation reaction further comprises separation and purification, and the separation and purification method is preferably column chromatography, and the eluent of the column chromatography is preferably, but not limited to, a mixed solvent of petroleum ether and ethyl acetate.

[0060] As an improved scheme of the above scheme, the trifluoromethylation reaction further comprises separation and purification, and the separation and purification method is selected from any one or more of column chromatography, liquid chromatography, distillation and recrystallization.

[0061] Example 1

[0062] Into a 10 mL undivided electrolysis cell, non-cyclic enamide compound (shown in formula 1-a) (0.3 mmol, 75.4 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N, N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μL) were added in sequence; graphite block (size: 10 mm x 10 mm x 0.3 mm) was inserted as anode and platinum sheet (size: 10 mm x 10 mm x 0.2 mm) as cathode, and direct current power supply was 10 mA, and the reaction was stirred at room temperature. After the reaction was completed (monitored by TLC), the obtained reaction solution was poured into 15 mL water, and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL saturated brine. The organic phase was dried with anhydrous sodium sulfate, concentrated to remove the solvent by rotary evaporator, and separated by column chromatography (the volume ratio of petroleum ether to ethyl acetate was 12:1) to obtain 77.8 mg of the target product (shown in formula 1-b), with a yield of 81%.

[0063] The structure of the obtained product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum, as shown in Figure 1 , Figure 2 and Figure 3 The structure characterization data are as follows:

[0064] 1 HNMR (400 MHz, CDCl3) δ 7.49-7.41 (m, 3H), 7.34-7.28 (m, 5H), 7.17-7.15 (m, 2H), 5.46 (q, J = 8.1 Hz, 1H), 4.52 (s, 2H), 2.25 (s, 3H); 13CNMR (101 MHz, CDC13) δ 169.8, 149.7 (q, J = 5.9 Hz), 136.4, 132.8, 130.6, 128.8 (q, J = 2.1 Hz), 128.49, 128.51, 128.4, 127.5, 122.0 (q, J = 270.2 Hz), 116.7 (q, J = 34.9 Hz), 49.4, 22.4; 19 F NMR (377 MHz, CDC13) δ -55.94.

[0065]

[0066] Example 2

[0067] Into a 10 mL undivided electrolysis cell, non-cyclic enamide compound (shown in Formula 2-a) (0.3 mmol, 79.6 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μL) were added successively; graphite block (size: 10 mm x 10 mm x 0.3 mm) as anode and platinum sheet (size: 10 mm x 10 mm x 0.2 mm) as cathode were inserted, and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL water and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL saturated brine. The organic phase was dried over anhydrous sodium sulfate, concentrated to remove the solvent by rotary evaporator, and separated by column chromatography (volume ratio of petroleum ether: ethyl acetate was 12:1) to obtain 69.1 mg of the target product (shown in Formula 2-b), with a yield of 69%.

[0068] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 4 , Figure 5 and Figure 6 The structure characterization data are as follows:

[0069] 1 HNMR (400 MHz, CDC13) δ 7.32-7.26 (m, 3H), 7.24 (s, 4H), 7.19-7.16 (m, 2H), 5.41 (q, J = 8.2 Hz, 1H), 4.53 (s, 2H), 2.41 (s, 3H), 2.25 (s, 3H); 13C NMR (101 MHz, CDC13) δ 170.0, 149.8 (q, J = 5.9 Hz), 141.1, 136.6, 129.9, 129.4, 128.8 (q, J = 2.0 Hz), 128.6, 128.5, 127.6, 122.2 (q, J = 270.2 Hz), 116.3 (q, J = 35.0 Hz), 49.5, 22.5, 21.4; 19 F NMR (377 MHz, CDC13) δ -55.92.

[0070]

[0071] Example 3

[0072] Into a 10 mL undivided electrolysis cell, non-cyclic olefinamides compound (shown in Formula 3-a) (0.3 mmol, 98.2 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μί) were added successively; graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted, and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL of water and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporator to remove the solvent, and separated by column chromatography (volume ratio of petroleum ether: ethyl acetate was 12: 1) to obtain 87.7 mg of the target product (shown in Formula 3-b) with a yield of 74%.

[0073] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 7 , Figure 8 and Figure 9 The structure characterization data are as follows:

[0074] 1 H NMR (400 MHz, CDC13) δ 7.69-7.63 (m, 4H), 7.51-7.46 (m, 2H), 7.45-7.40 (m, 3H), 7.36-7.27 (m, 3H), 7.24-7.20 (m, 2H), 5.50 (q, J = 8.2 Hz, 1H), 4.60 (s, 2H), 2.30 (s, 3H); 13CNMR (101 MHz, CDC13) δ 170.0, 149.5 (q, J = 5.7 Hz), 143.5, 139.7, 136.5, 131.5, 129.3 (q, J = 2.0 Hz), 128.9, 128.6, 128.5, 128.0, 127.6, 127.2, 127.1, 122.1 (q, J = 270.1 Hz), 116.7 (q, J = 35.2 Hz), 49.6, 22.5; 19 F NMR (377 MHz, CDC13) δ -55.88.

[0075]

[0076] Example 4

[0077] Into a 10 mL undivided electrolysis cell, non-cyclic olefinamides compound (shown in Formula 4-a) (0.3 mmol, 95.8 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μL) were added successively; graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted, and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL water, and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL saturated brine. The organic phase was dried over anhydrous sodium sulfate, concentrated to remove the solvent by rotary evaporator, and separated by column chromatography (volume ratio of petroleum ether: ethyl acetate was 12: 1) to obtain 72.1 mg of the target product (shown in Formula 4-b), with a yield of 62%.

[0078] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 10 , Figure 11 and Figure 12 , and the structure characterization data are as follows:

[0079] 1 H NMR (400 MHz, CDC13) δ 7.67 (d, J = 8.1 Hz, 2H), 7.42 (d, J = 8.1 Hz, 2H), 7.34 - 7.23 (m, 3H), 7.13 (dd, J = 7.6, 1.9 Hz, 2H), 5.58 (q, J = 8.0 Hz, 1H), 4.53 (s, 2H), 2.26 (s, 3H); 13C NMR (101 MHz, CDC13) δ 169.8, 148.4 (q, J = 6.0 Hz), 136.6, 136.1, 132.7, 132.3, 129.3 (q, J = 1.8 Hz), 128.7, 128.4, 127.9, 125.6 (q, J = 3.8 Hz), 122.7 (q, J = 99.3 Hz), 118.1 (q, J = 35.0 Hz, 1H), 49.8, 22.5; 19 F NMR (377 MHz, CDC13) δ -55.93, -63.00.

[0080]

[0081] Example 5

[0082] Into a 10 mL undivided electrolysis cell, non-cyclic olefinamides compound (shown in Formula 5-a) (0.3 mmol, 82.9 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μί) were added successively; graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted, and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL of water and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate, concentrated by rotary evaporator to remove the solvent, and separated by column chromatography (volume ratio of petroleum ether: ethyl acetate was 10: 1) to obtain 68.2 mg of the target product (shown in Formula 5-b) with a yield of 66%.

[0083] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 13 , Figure 14 and Figure 15 The structure characterization data are as follows:

[0084] 1 H NMR (400 MHz, CDC13) δ 7.72-7.68 (m, 2H), 7.40 (d, J = 8.3 Hz, 2H), 7.33-7.27 (m, 3H), 7.10 (dd, J = 7.4, 2.2 Hz, 2H), 5.61 (q, J = 8.0 Hz, 1H), 4.54 (s, 2H), 2.25 (s, 3H); 13C NMR (101 MHz, CDC13) δ 169.8, 148.0 (q, J = 5.9 Hz), 137.5, 135.9, 132.2, 129.4 (q, J = 2.0 Hz), 128.7, 128.2, 127.9, 121.7 (q, J = 270.6 Hz), 118.3 (q, J = 35.3 Hz), 117.8, 114.3, 50.0, 22.5; 19 F NMR (377 MHz, CDC13) δ -55.86.

[0085]

[0086] Example 6

[0087] To a 10 mL undivided electrolysis cell was added non-cyclic olefinamides compound (shown in Formula 6-a) (0.3 mmol, 90.4 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μί); graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL of water and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate and concentrated to remove the solvent using a rotary evaporator and the target product (shown in Formula 6-b) was obtained by column chromatography (volume ratio of petroleum ether: ethyl acetate was 14: 1) in a yield of 60.9 mg, 55%.

[0088] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 16 , Figure 17 and Figure 18 The structure characterization data are as follows:

[0089] 1 HNMR (400 MHz, CDC13) δ 7.92-7.82 (m, 4H), 7.62-7.52 (m, 2H), 7.41 (dd, J = 8.5, 1.8 Hz, 1H), 7.35-7.26 (m, 3H), 7.19 (dd, J = 7.8, 1.8 Hz, 2H), 5.57 (q, J = 8.2 Hz, 1H), 4.58 (s, 2H), 2.32 (s, 3H); 13C NMR(101MHz, CDCl3)δ170.1,149.8(q,J=5.9Hz),136.5,134.1,132.6,130.1,129.4,128.6,128 .5,127.7,127.7,127.7,126.9,125.2,122.2(q,J=270.3Hz),116.8(q,J=35.0Hz),49.7,22.6; 19 F NMR (377MHz, CDCl3) -55.76.

[0090]

[0091] Example 7

[0092] A noncyclic enamide compound (shown in Formula 7-a) (0.3 mmol, 85.7 mg), sodium trifluoromethyl sulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), and sulfuric acid (0.45 mmol, 24.5 μL) were added sequentially to a 10 mL non-separated electrolytic cell. A graphite block (10 mm × 10 mm × 0.3 mm) and a platinum sheet (10 mm × 10 mm × 0.2 mm) were inserted as the anode. The cell was powered by a 10 mA DC power supply, and the reaction was stirred at room temperature. After the reaction was complete (monitored by TLC), the resulting reaction solution was poured into 15 mL of water and extracted with ethyl acetate (3 × 15 mL). The combined organic phases were washed with 15 mL of saturated brine. The organic phase was dried with anhydrous sodium sulfate, concentrated by rotary evaporation to remove the solvent, and separated by column chromatography (petroleum ether: ethyl acetate volume ratio of 12:1) to obtain 99.8 mg of the target product (shown in Formula 7-b), with a yield of 94%.

[0093] The structure of the obtained product was characterized, and the proton NMR, carbon NMR, and fluorine NMR spectra are shown below. Figure 19 , Figure 20 and Figure 21 As shown, the structural characterization data is as follows:

[0094] 1 HNMR (400MHz, CDCl3) δ7.45 (ddd, J=8.0, 2.0, 1.1Hz, 1H), 7.36 (t, J=7.9Hz, 1H), 7.33-7.25 (m, 4H) ,7.23-7.19(m,1H),7.14(dd,J=7.7,1.8Hz,2H),5.50(q,J=8.0Hz,1H),4.52(s,2H),2.25(s,3H); 13C NMR (101 MHz, CDC13) δ 169.8, 148.3 (q, J = 5.9 Hz), 136.2, 134.7, 130.7, 129.8, 128.6 128.4, 127.7, 127.2, 127.2, 121.8 (q, J = 270.4 Hz), 117.6 (q, J = 35.0 Hz), 49.6, 22.4; 19 F NMR (377 MHz, CDC13) δ -55.95.

[0095]

[0096] Example 8

[0097] To a 10 mL undivided electrolysis cell was added non-cyclic olefinamides compound (shown in Formula 8-a) (0.3 mmol, 79.6 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μί); graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL of water and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL of saturated brine. The organic phase was dried over anhydrous sodium sulfate and concentrated to remove the solvent using a rotary evaporator and the target product (shown in Formula 8-b) was isolated by column chromatography (volume ratio of petroleum ether: ethyl acetate = 12: 1) to give 73.1 mg of the target product in a yield of 73%.

[0098] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 22 , Figure 23 and Figure 24 The structure characterization data are as follows:

[0099] 1 H NMR (400 MHz, CDC13) δ 7.50-7.39 (m, 3H), 7.36-7.31 (m, 2H), 7.10 (d, J = 7.9 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 5.45 (q, J = 8.2 Hz, 1H), 4.48 (s, 2H), 2.32 (s, 3H), 2.24 (s, 3H); 13C NMR (101 MHz, CDC13) δ 169.9, 149.8 (q, J = 5.9 Hz), 137.3, 133.4, 132.9, 130.7, 129.2, 128.9, 128.6, 128.6, 122.1 (q, J = 270.1 Hz), 116.8 (q, J = 35.0 Hz), 49.2, 22.5, 21.1; 19 F NMR (377 MHz, CDC13) δ -55.86.

[0100]

[0101] Example 9

[0102] Into a 10 mL undivided electrolysis cell, non-cyclic olefinamides compound (shown in Formula 9-a) (0.3 mmol, 52.6 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μL) were added successively; graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted, and a direct current power supply of 10 mA was used to stir the reaction at room temperature. After the reaction was completed (monitored by TLC), the resulting reaction solution was poured into 15 mL water, and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL saturated brine. The organic phase was dried over anhydrous sodium sulfate, concentrated to remove the solvent by rotary evaporator, and separated by column chromatography (volume ratio of petroleum ether: ethyl acetate was 15: 1) to obtain 40.1 mg of the target product (shown in Formula 9-b), with a yield of 56%.

[0103] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 25 , Figure 26 and Figure 27 respectively, and the structure characterization data are as follows: 1 H NMR (400 MHz, CDC13) δ 7.47-7.37 (m, 3H), 7.37-7.33 (m, 2H), 5.69 (q, J = 8.1 Hz, 1H), 2.94 (s, 3H), 2.14 (s, 3H); 13 C NMR (101 MHz, CDC13) δ 170.3, 151.6 (q, J = 5.7 Hz), 133.1, 130.6, 1286 122.4 (q, J = 269.9 Hz), 114.6 (q, J = 35.2 Hz), 35.2, 22.3; 19 F NMR (377 MHz, CDC13) δ -55.73.

[0104]

[0105] Example 10

[0106] To a 10 mL undivided electrolysis cell was added non-cyclic olefinamides compound (shown in Formula 10-a) (0.3 mmol, 74.5 mg), sodium trifluoromethylsulfinate (0.9 mmol, 140.4 mg), N,N-dimethylformamide (5 mL), sulfuric acid (0.45 mmol, 24.5 μL) sequentially; graphite block as anode (size: 10 mm x 10 mm x 0.3 mm) and platinum sheet as cathode (size: 10 mm x 10 mm x 0.2 mm) were inserted, and a direct current power supply was provided with 10 mA, and the reaction was stirred at room temperature. After the reaction was completed (TLC tracking monitoring), the resulting reaction solution was poured into 15 mL of water, and extracted with ethyl acetate (3 x 15 mL). The combined organic phase was washed with 15 mL of saturated brine. The organic phase was dried with anhydrous sodium sulfate, concentrated to remove the solvent with a rotary evaporator, and separated by column chromatography (petroleum ether: ethyl acetate, volume ratio 50:1) to obtain 46.4 mg of the target product (shown in Formula 10-b), with a yield of 47%.

[0107] The structure of the resulting product was characterized by nuclear magnetic resonance hydrogen spectrum, nuclear magnetic resonance carbon spectrum and nuclear magnetic resonance fluorine spectrum as shown in Figure 28 , Figure 29 and Figure 30 , and the structure characterization data are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.43-7.38 (m, 2H), 7.38-7.31 (m, 3H), 5.77 (q, J = 8.0 Hz, 1H), 2.53 (s, 3H), 1.37 (s, 9H); 13 C NMR (101 MHz, CDCl3) δ 172.3, 151.4, 146.6 (q, J = 6.6 Hz), 134.5, 129.7, 128.7 (q, J = 2.3 Hz), 127.9, 122.1 (q, J = 270.2 Hz), 119.2 (q, J = 35.2 Hz), 84.3, 27.6, 26.1; 19 F NMR (377 MHz, CDCl3) -56.85.

[0108]

[0109] One or more embodiments of the specification are intended to encompass all such substitutions, modifications and variations as fall within the broad scope of the appended claims. Accordingly, any omission, modification, substitution, improvement, etc. made in the spirit and principle of one or more embodiments of the specification shall be included in the scope of protection of the present disclosure.

Claims

1. An electrochemical oxidation synthesis method of an E-type β-trifluoromethyl enamide compound, characterized by, The method comprises the following steps: In a reactor equipped with electrode sheets, non-cyclic enamide compounds, trifluoromethyl sulfinate, additives and solvents are stirred and mixed, and under electrochemical conditions, a β-C(sp2)-H trifluoromethylation reaction is carried out to obtain a series of E-type β-trifluoromethyl enamide compounds with high selectivity. The E-type β-trifluoromethyl enamide compound has the structure shown in formula (I): The E-type β-trifluoromethyl enamide compound includes: The non-cyclic enamide compound has the structure shown in formula (II): The trifluoromethyl sulfinate has the structure shown in formula (III): wherein M is a metal cation; The additive is selected from any one or a mixture of several of formic acid, acetic acid, sulfuric acid, hydrochloric acid, trifluoroacetic acid and phosphoric acid; The solvent is selected from any one or a mixture of several of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, methanol, ethanol, tetrahydrofuran and dichloromethane; The molar ratio of the non-cyclic enamide compound, the trifluoromethyl sulfinate and the additive is 1.0:(1.0-5.0):(0.5-3.0); the starting concentration of the non-cyclic enamide compound is 0.02-0.1 mol / L; The reactor used in the electrochemical conditions is a non-separated electrolytic cell, the power supply is a direct current stabilized power supply, and the reaction is carried out under constant current conditions, with an electric current of 5-15 mA; The trifluoromethylation reaction temperature is 0-60°C; the reaction time is 2-10.

2. The electrochemical oxidation synthesis method of claim 1, wherein, The trifluoromethylation reaction further includes separation and purification; the separation and purification method is selected from any one or more of column chromatography, liquid chromatography, distillation and recrystallization.

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