CN111155141B - Method for electrochemically synthesizing gem-difluoroolefin - Google Patents

Abstract

The invention relates to a method for electrochemically synthesizing gem-difluoroolefin. Specifically, the method takes a nickel electrode as a cathode and a zinc electrode as an anode, and adopts constant current for electrifying to react a trifluoromethyl olefin compound and an alkyl electrophilic reagent in a solvent to obtain a geminal difluoroolefin compound. The method uses olefin with rich sources and optimal atom economy as a main raw material, the used reducing agent zinc rod is stable and safe, the experimental steps are easy to operate, and the method has good functional group compatibility and high regioselectivity.

Description

A kind of method for electrochemical synthesis of geminal difluoroalkene

technical field

The invention relates to the technical field of organic synthesis, in particular to a method for electrochemically synthesizing geminal difluoroolefins.

Background technique

Compared with ordinary non-fluorine compounds, fluorine-containing compounds have many different characteristics, which makes such compounds have extremely important applications in the fields of medicine and pesticides. Difluoroolefins are bioisosteres of ketone carbonyl groups, which have many important applications in the fields of biology and pharmacy. Monofluoroolefins, which are bioisosteres of amide bonds, also often require difluoroolefins as precursors for the preparation of Therefore, difluoroalkenes are also important intermediates in organic synthesis. The preparation of transition metal-catalyzed difluoroalkenes is a relatively common and efficient synthesis method for such compounds in recent years, and metals such as iridium and nickel are used to synthesize such compounds. However, in the process of using transition metal to catalyze the synthesis of such compounds, various metal catalysts and ligands need to be added or catalysts need to be prepared in advance, and there are limitations in the types of substrates, poor reaction economy, poor reaction selectivity, and some Less safe reducing agents are involved in the preparation process and other disadvantages. Based on the above problems, how to develop a universal, efficient and highly selective synthetic method for geminal difluoroolefins is a scientific problem that needs to be solved urgently.

At present, there are traditionally the following four methods based on the synthesis of geminal difluoroolefins:

The above methods all require the use of an equivalent amount of additional chemical additives, as well as dangerous reducing substances such as zinc powder and magnesium powder, and have the characteristics of low efficiency and poor selectivity.

There are three types of methods for the synthesis of geminal difluoroolefins based on transition metal catalysis:

1. Nickel-catalyzed redox active esters of alkyl carboxylic acids and trifluoromethyl olefins to synthesize aryl difluoroolefins, as shown in reaction formula (1). The method was published by Professor Fu Yao and his research group in Chem.Sci., 2019, 10, 809-814. This method requires the additional use of expensive nickel catalyst ligands and unsafe zinc powder as reducing agents, which has great limitations.

2. Nickel-catalyzed alkyl halides and trifluoromethyl olefin compounds to synthesize aryl gem-difluoroolefin compounds, as shown in reaction formula (2). This method was published by Wang Chuan's research group in ACS Catal., 2018, 8, 10, 9245-9251. In this reaction, it is still necessary to use expensive nickel catalysts and ligands, as well as unsafe zinc powder as a reducing agent, and an additional equivalent of cesium fluoride needs to be added, which reduces the practical value of the reaction, and the reaction is very economical. Adverse.

3. The use of iridium photocatalyst and light to realize the synthesis of geminal difluoroolefin compounds has also been partially reported, as shown in reaction formula (3). The method was published by Professor Zhou Lei and his research group in J.Org.Chem.2016, 81, 17, 7908-7916. This method uses an expensive iridium catalyst, and the substrate range is relatively limited, and an equivalent amount of base and corresponding photochemical equipment are required, so the method is not economical and has no industrial-scale production value.

The previous methods for synthesizing geminal difluoroalkenes all have problems such as limited substrates and poor practicability of synthetic methods. Therefore, it is an urgent problem to seek a method that is easy to operate, easy to obtain raw materials, and capable of synthesizing such compounds and their derivatives in large quantities.

SUMMARY OF THE INVENTION

The purpose of the present invention is to provide an efficient and convenient method for synthesizing asymmetric alkyl internal alkyne compounds with a wide range of substrates using cheap nickel catalysts and alkenes with abundant sources and the best atom economy as the main raw materials.

The present invention specifically adopts the following technical solutions:

Taking the nickel electrode as the cathode and the zinc electrode as the anode, energizing with a constant current, the trifluoromethyl olefin compound of the formula I-a and the alkyl electrophile of the formula I-b are reacted in a solvent to obtain the geminal difluoroolefin compound of the formula I ;

R-X formula I-b;

in,

选自芳基或取代芳基，其中任选地一个或多个环碳原子或非末端碳原子独立地被N或O原子替代；

is selected from aryl or substituted aryl, wherein optionally one or more ring carbon atoms or non-terminal carbon atoms are independently replaced by N or O atoms;

R is selected from substituted or unsubstituted alkyl or cycloalkyl wherein optionally one or more ring carbon atoms or non-terminal carbon atoms are independently replaced by N or O atoms;

X is iodine or redox active ester group,

Provided that R is not benzyl.

选自被以下取代基取代的芳基：卤素、羟基、氨基、氰基、羧基、烷基、硅烷基、硫烷基、环烷基、烯基、炔基、酯基、酰胺基、酰基、磺酰基或芳基，其中所述烷基、硅烷基、硫烷基、环烷基、烯基、炔基、酯基、酰胺基、酰基、磺酰基或芳基取代基任选地被卤素、羟基、氨基、氰基、羧基或烷基取代，并且其中任选地一个或多个环碳原子或非末端碳原子独立地被N或O原子替代。In some embodiments,

Aryl substituted with the following substituents: halogen, hydroxy, amino, cyano, carboxyl, alkyl, silyl, sulfanyl, cycloalkyl, alkenyl, alkynyl, ester, amido, acyl, Sulfonyl or aryl, wherein the alkyl, silyl, sulfanyl, cycloalkyl, alkenyl, alkynyl, ester, amido, acyl, sulfonyl or aryl substituents are optionally substituted by halogen, hydroxy, amino, cyano, carboxyl or alkyl substituted, and wherein optionally one or more ring carbon atoms or non-terminal carbon atoms are independently replaced by N or O atoms.

In some embodiments, R is selected from alkyl or cycloalkyl substituted with the following substituents: fluorine, chlorine, bromine, hydroxy, amino, cyano, carboxyl, alkyl, silyl, sulfanyl, cycloalkyl , alkenyl, alkynyl, ester, amido, acyl, sulfonyl or aryl, wherein the alkyl, silyl, sulfanyl, cycloalkyl, alkenyl, alkynyl, ester, amido, An acyl, sulfonyl, or aryl substituent is optionally substituted with halogen, hydroxy, amino, cyano, carboxy, or alkyl, and wherein optionally one or more ring carbon atoms or non-terminal carbon atoms are independently N or O atom substitution.

In some embodiments, redox-active ester groups include N-hydroxyphthalimide carboxylate groups, 1-hydroxybenzotriazole carboxylate groups, and the like, preferably N-hydroxyphthalimide Amine C _1-12 carboxylate group and 1-hydroxybenzotriazole C _1-12 carboxylate group, and more preferably N-hydroxyphthalimide C _1-6 carboxylate group and 1- Hydroxybenzotriazole C _1-6 carboxylate group.

As used herein, an alkyl, silyl, sulfanyl, alkenyl or alkynyl group contains 1 to 30 carbon atoms, preferably 1 to 20 carbon atoms, more preferably 1 to 12 carbon atoms, even more preferably 1 to 6 carbon atoms. In some embodiments, the alkyl group is selected from methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-pentyl, n-hexyl, and the like.

As used herein, a cycloalkyl group contains 3 to 30 carbon atoms, preferably 3 to 20 carbon atoms, more preferably 3 to 12 carbon atoms, even more preferably 3 to 6 carbon atoms. In some embodiments, the cycloalkyl group is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.

Aryl, as used herein, refers to a group comprising an aromatic moiety, having 6 to 30 carbon atoms, preferably 6 to 20 carbon atoms, more preferably 3 to 12 carbon atoms, even more preferably 3 to 6 carbon atoms carbon atom. In some embodiments, the aryl group is selected from phenyl, naphthyl, and the like.

As used herein, halogen includes fluorine, chlorine, bromine and iodine.

As used herein, hydroxyl refers to the -OH group.

As used herein, amino refers to the _-NH2 group.

As used herein, cyano refers to the -CN group.

As used herein, a carboxyl group refers to a -COOH group.

As used herein, sulfanyl refers to an -S-alkyl group.

As used herein, an ester group refers to a -C(=O)O-alkyl group or a -OC(=O)-alkyl group.

As used herein, amido refers to a -C(=O)NHR' group, where R' is hydrogen or alkyl.

As used herein, acyl refers to a -C(=O)R' group, where R' is hydrogen or alkyl.

As used herein, sulfonyl refers to a -S(=O)2R' group, where R' is _hydrogen or alkyl.

In some embodiments, the geminal difluoroolefin compound may contain protecting groups such as Boc, Ac, Bz, CBz, Fmoc, MOM, a series of silicon-based protecting groups, and the like.

In some embodiments, the nickel electrode is a single nickel sheet having a porous nickel foam structure.

In some embodiments, the zinc electrode is a solid high purity zinc flake or rod.

In some embodiments, the galvanostatic range is 1-100 mA/cm ² , such as 1-50 mA/cm ² , such as 1-20 mA/cm ² , preferably 5 mA/cm ² .

In some embodiments, the solvent is a conductive organic solvent, preferably selected from N,N-dimethylformamide, N,N-dimethylacetamide, dichloromethane, dichloroethane, N-methyl Pyrrolidone, 1,3-dimethylpropylene urea, and hexamethylphosphoramide, and contain electrolytes such as tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium iodide, tetrabutylammonium fluoroborate , tetrabutylammonium phosphate fluoride, benzyltrimethylammonium chloride, etc. In some embodiments, the reaction can be carried out in 0.1M tetrabutylammonium bromide in N,N-dimethylformamide solvent or 0.1M tetrabutylammonium iodide in N,N-dimethylformamide solvent .

In some embodiments, the ratio of the trifluoromethyl olefin compound, the alkyl electrophile, and the solvent is 0.2-2 mmol: 1.2-1.5 equiv: 2 mL (preferably 0.2 mmol: 1.5 equiv: 2 mL), The concentration of the reaction solution can be 0.01-1 mol/L.

It should be noted that the electrode needs to be at least 1cm below the liquid surface.

In some embodiments, the reaction temperature is 10-40° C., and the reaction time is based on the amount of materials added, which conforms to Faraday’s law of electrolysis.

In a specific embodiment, the reaction equation of the method of the present invention is as follows:

和R如以上所限定的。in

and R is as defined above.

In certain specific embodiments of the present invention, the reaction specifically comprises the following steps:

(1) place tetrabutylammonium bromide etc. in the reaction vessel, according to the difference of the reactant physical properties, the solid reactant is added in the reactor vessel and then the solvent is added, the liquid reactant is added and stirred again after the solid is dissolved and stirred For five minutes, add the corresponding zinc electrode and nickel electrode, adjust and fix the position of the electrode, the electrode needs to be submerged at least 1cm below the liquid surface, adjust the constant current required by the device, and place it at 10 ~ 40 ℃ to stir the reaction, Connect the electrodes to the power source and power up. The reaction time varies according to the amount of material added, which conforms to Faraday's law of electrolysis. Wherein, the ratio of the above-mentioned trifluoromethyl olefin compound, alkyl electrophile, and solvent is 0.2-2 mmol: 1.2-1.5 equivalent: 2 mL (preferably 0.2 mmol: 1.5 equivalent: 2 mL).

(2) Add ethyl acetate, add crude silica gel, and mix the sample.

(3) The sample obtained in (2) was subjected to column chromatography to separate and purify the crude product. Petroleum ether or a mixed solution of petroleum ether and ethyl acetate was used as the eluent, and the ratio of petroleum ether to ethyl acetate in the mixed solution was adjusted according to the different substrates used.

Compared with the prior art, the present invention provides a novel preparation method of geminal difluoroolefin, which comprises the following steps: using the trifluoromethyl olefin compound of formula I-a and the alkyl electrophile of formula I-b as raw materials, and reacting with the electrode Under electrolysis, the geminal difluoroolefin of formula I is obtained. The method of the invention directly uses the trifluoromethyl olefin compound as the raw material to participate in the reaction, and the reaction system and the feeding method are extremely simple. The used reducing agent zinc rod is relatively stable and safe, and the used trifluoromethyl olefin compound and alkyl electrophile are easy to be prepared in laboratory and in large quantities, and are very convenient in practical application.

The present invention provides the following beneficial effects at least:

(1) Compared with the prior art, the present invention directly uses a trifluoromethyl olefin compound that is simple and easy to obtain as a raw material to participate in the reaction, and the experimental steps are very easy to operate. The used reducing agent zinc rod is relatively stable, safe and abundant, which is very convenient in practical application.

(2) The reaction has good functional group compatibility and high regioselectivity.

Description of drawings

FIG. 1 is the hydrogen NMR spectrum of the product of Example 1. FIG.

FIG. 2 is the hydrogen NMR spectrum of the product of Example 2. FIG.

FIG. 3 is the hydrogen NMR spectrum of the product of Example 3. FIG.

FIG. 4 is the hydrogen NMR spectrum of the product of Example 4. FIG.

FIG. 5 is the hydrogen NMR spectrum of the product of Example 5. FIG.

FIG. 6 is the hydrogen NMR spectrum of the product of Example 6. FIG.

FIG. 7 is the hydrogen NMR spectrum of the product of Example 7. FIG.

FIG. 8 is the hydrogen NMR spectrum of the product of Example 8. FIG.

FIG. 9 is the hydrogen NMR spectrum of the product of Example 9. FIG.

FIG. 10 is the hydrogen NMR spectrum of the product of Example 10. FIG.

FIG. 11 is the hydrogen NMR spectrum of the product of Example 11. FIG.

FIG. 12 is the hydrogen NMR spectrum of the product of Example 12. FIG.

Detailed ways

In order to further illustrate the present invention, the preparation method of the geminal difluoroolefin of the present invention will be described in detail below with reference to specific examples.

Tetrabutylammonium bromide (TBAB) was purchased from Tokyo Chemical Industry (TCI), N,N-dimethylformamide (DMF) was purchased from Adamas Company, and the rest of the raw materials were self-made.

Example 1

The reaction formula of this embodiment is as follows:

Specific steps are as follows:

(1) Under air, p-phenyltrifluoromethyl olefin (0.2 mmol), CyCOONPhth (0.3 mmol) and tetrabutylammonium bromide (0.2 mmol) were added to a 15 mL thick-walled test tube containing magnon. 2 mL of N,N-dimethylformamide was added to the test tube, and the mixture was stirred for five minutes in a magnetic stirrer at room temperature. Insert the nickel electrode and the zinc electrode into the test tube and fix it well (the electrode is submerged 2cm below the liquid surface), adjust the current of the galvanostatic reactor to 10mA, connect the power source and the electrode, and then energize for 1.5 hours.

(2) Add ethyl acetate, add about 10 g of crude silica gel, and mix the samples with a rotary evaporator.

(3) The sample obtained in (2) was subjected to column chromatography to separate and purify the crude product. Petroleum ether was used as the eluent.

The obtained product was a white solid with a yield of 85% and a product purity of 99%. ¹ H NMR (400MHz, CDCl3) δ 7.59 (m, J=8.4Hz, 4H), 7.49-7.31 (m, 6H), 2.30 (d, J=7.1Hz, 2H), 1.87-1.45 (m, 6H) ), 1.38–0.81 (m, 6H). The H NMR spectrum is shown in Figure 1.

Example 2

The compound of Example 2 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a white solid with a yield of 84% and a product purity of 99%. ¹ H NMR (400 MHz, CDCl3) δ 7.69-7.50 (m, 4H), 7.49-7.27 (m, 5H), 2.37 (dd, J=2.7, 2.2 Hz, 2H), 0.83 (s, 9H). The H NMR spectrum is shown in Figure 2.

Example 3

The compound of Example 3 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The resulting product was a white solid with a yield of 78% and a product purity of 99%. ¹ H NMR (500MHz, CDCl3) δ 7.58 (dd, J=12.1, 4.7Hz, 4H), 7.42 (dd, J=14.9, 7.8Hz, 4H), 7.33 (t, J=7.2Hz, 1H), 7.15 (d, J=8.6 Hz, 2H), 6.73 (d, J=8.6 Hz, 2H), 2.84 (s, 2H), 1.19 (s, 6H). The hydrogen NMR spectrum is shown in Figure 3.

Example 4

The compound of Example 4 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 68% and a product purity of 99%. ¹ H NMR (500MHz, CDCl3) δ 7.57 (dd, J=14.8, 7.9 Hz, 4H), 7.44 (t, J=7.6 Hz, 2H), 7.38-7.30 (m, 3H), 7.23 (tt, J =14.4,7.2Hz,4H),7.11(d,J=7.0Hz,2H),4.28(t,J=41.3Hz,1H),3.83(t,J=29.6Hz,1H),2.78(d,J = 6.2 Hz, 2H), 2.58 (d, J = 5.4 Hz, 2H), 1.49–1.11 (m, 9H). The H NMR spectrum is shown in Figure 4.

Example 5

The compound of Example 5 was prepared by a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 64% and a product purity of 99%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.99-7.87 (m, 2H), 7.52 (d, J=8.2 Hz, 1H), 7.49-7.41 (m, 1H), 7.38-7.27 (m, 4H), 7.22–7.09 (m, 4H), 7.03 (d, J=6.5Hz, 2H), 4.35 (d, J=6.5Hz, 1H), 3.80 (d, 1H), 3.00–2.59 (m, 4H), 1.28 (s,9H). H NMR spectrum is shown in Figure 5.

Example 6

The compound of Example 6 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a white solid with a yield of 54% and a product purity of 99%. ¹ H NMR (400MHz, CDCl3) δ 7.59 (m, J=8.4Hz, 4H), 7.49-7.31 (m, 6H), 2.30 (d, J=7.1Hz, 2H), 1.87-1.45 (m, 6H) ), 1.38–0.81 (m, 6H). The H NMR spectrum is shown in Figure 6.

Example 7

The compound of Example 7 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 68% and a product purity of 99%. ¹ H NMR (400 MHz, chloroform-d) δ 7.60 (d, J=8.3 Hz, 2H), 7.33 (d, J=8.2 Hz, 2H), 7.30–7.14 (m, 4H), 7.14–6.94 (dd , 2H), 4.31 (d, J=9.5Hz, 1H), 3.78 (d, J=8.3Hz, 1H), 2.75 (td, J=14.2, 13.5, 6.4Hz, 2H), 2.55 (dd, J= 5.6, 3.0Hz, 2H), 1.36(s, 9H).

Example 8

The compound of Example 8 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 63% and a product purity of 99%. ¹ H NMR (400MHz, chloroform-d) δ 7.36 (d, J=7.9Hz, 2H), 7.29 (d, J=8.3Hz, 2H), 3.81 (d, J=48.8Hz, 0H), 3.48– 3.12 (m, 1H), 3.07–2.93 (m, 2H), 2.92–2.76 (m, 1H), 2.40 (dt, J=34.4, 12.4Hz, 1H), 1.80 (ddt, J=24.0, 12.1, 6.7 Hz, 4H), 1.70–1.58 (m, 1H), 1.46 (s, 9H), 1.31 (d, J=6.7Hz, 6H).

Example 9

The compound of Example 9 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 71% and a product purity of 99%. ¹ H NMR (400MHz, chloroform-chloroform-d) δ 7.48 (d, J=7.6Hz, 2H), 7.26 (dd, J=9.1, 5.4Hz, 4H), 7.09 (d, J=7.3Hz, 2H) ,4.27(d,J＝8.8Hz,1H),3.83(d,J＝9.1Hz,1H),2.76(d,J＝6.7Hz,2H),2.55(d,J＝6.9Hz,2H),1.36 (s, 9H), 0.27(s, 9H).

Example 10

The compound of Example 10 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 90% and a product purity of 99%. ¹ H NMR (400 MHz, chloroform-d) δ 7.46 (d, J=6.7 Hz, 2H), 7.28 (d, J=7.6 Hz, 2H), 2.35 (s, 2H), 1.60–1.04 (m, 10H) ),0.75(s,3H),0.26(s,9H).

Example 11

The compound of Example 11 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 65% and a product purity of 99%. ¹ H NMR (400 MHz, chloroform-d) δ 8.00 (d, J=8.0 Hz, 2H), 7.33-7.18 (m, 6H), 7.09 (d, J=7.2 Hz, 2H), 4.38 (dd, J ＝7.1Hz, 2H), 4.30(d, J＝9.1Hz, 1H), 3.80(d, J＝7.5Hz, 1H), 2.85–2.63(m, 2H), 2.57(d, J＝6.9Hz, 2H) ),1.40(t,J=6.9Hz,3H),1.36(s,9H).

Example 12

The compound of Example 12 was prepared according to a method similar to that of Example 1, and the reaction formula was as follows:

The obtained product was a clear oily liquid with a yield of 92% and a product purity of 99%. ¹ H NMR (400MHz, chloroform-d) δ 7.20 (d, J=8.2Hz, 2H), 6.85 (d, J=8.7Hz, 2H), 5.86 (tdd, J=16.7, 8.0, 5.5Hz, 1H) ), 5.03(dd, J=25.4, 13.6Hz, 2H), 3.96(t, J=6.3Hz, 2H), 2.30(s, 2H), 2.24(dd, J=7.4Hz, 2H), 1.88(p , J=6.6Hz, 2H), 1.61–1.08 (m, 10H), 0.75 (s, 3H).

It can be seen from the above examples that the method uses simple and readily available raw materials, and directly prepares the corresponding geminal difluoroolefins rapidly and directly under electrochemical action, and the preparation method is very simple and efficient.

The descriptions of the above embodiments are only used to help understand the method and the core idea of the present invention. It should be pointed out that for those skilled in the art, without departing from the principle of the present invention, several improvements and modifications can also be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims (16)

1. a method for preparing a geminal difluoroolefin compound, the method comprising: Taking the nickel electrode as the cathode and the zinc electrode as the anode, energizing with a constant current, the trifluoromethyl olefin compound of the formula I-a and the alkyl electrophile of the formula I-b are reacted in a solvent to obtain the geminal difluoroolefin compound of the formula I ;

in,

is selected from aryl or substituted aryl, wherein optionally one or more ring carbon atoms or non-terminal carbon atoms are independently replaced by N or O atoms; wherein said substituted aryl is selected from aryl substituted with the following substituents : halogen, hydroxyl, amino, cyano, carboxyl, alkyl, silyl, sulfanyl, cycloalkyl, alkenyl, alkynyl, ester, amide, acyl, sulfonyl or aryl, wherein the alkane radical, silyl, sulfanyl, cycloalkyl, alkenyl, alkynyl, ester, amido, acyl, sulfonyl or aryl substituents optionally substituted by halogen, hydroxy, amino, cyano, carboxyl or alkane base substitution; R is selected from substituted or unsubstituted alkyl or cycloalkyl wherein optionally one or more ring carbon atoms or non-terminal carbon atoms are independently replaced by N or O atoms; and X is iodine or redox active ester group, provided that R is not benzyl, wherein the solvent is a conductive organic solvent selected from N,N-dimethylformamide and N,N-dimethylacetamide, and contains an electrolyte selected from tetrabutylammonium bromide, tetrabutylammonium ammonium chloride and tetrabutylammonium iodide. 2. The method of claim 1, wherein R is selected from alkyl or cycloalkyl substituted with the following substituents: fluorine, chlorine, bromine, hydroxyl, amino, cyano, carboxyl, alkyl, silyl, sulfur alkyl, cycloalkyl, alkenyl, alkynyl, ester, amido, acyl, sulfonyl or aryl, wherein said alkyl, silyl, sulfanyl, cycloalkyl, alkenyl, alkynyl, Ester, amide, acyl, sulfonyl or aryl substituents are optionally substituted with halogen, hydroxy, amino, cyano, carboxyl or alkyl, and wherein optionally one or more ring carbon atoms or non-terminal carbons Atoms are independently replaced by N or O atoms. 3. The method of claim 1, wherein the redox-active ester groups comprise N-hydroxyphthalimide carboxylate groups and 1-hydroxybenzotriazole carboxylate groups. 4. The method of any one of claims 1-3, wherein the trifluoromethyl olefin compound of formula I-a, the alkyl electrophile of formula I-b and/or the geminal difluoroolefin compound of formula I comprise protecting groups. 5. The method of any one of claims 1-3, wherein the nickel electrode is a single nickel sheet having a porous nickel foam structure. 6. The method of any one of claims 1-3, wherein the zinc electrode is a solid high-purity zinc flake or rod. 7. The method of any one of claims 1-3, wherein the galvanostatic range is 1-100 mA/ ^cm2 . 8. The method of claim 7, wherein the galvanostatic range is 1-50 mA/ ^cm2 . 9. The method of claim 7, wherein the galvanostatic range is 1-20 mA/ ^cm2 . 10. The method of claim 7, wherein the galvanostatic current is 5 mA/ ^cm2 . 11. The method according to any one of claims 1-3, wherein in N,N-dimethylformamide solvent of 0.1M tetrabutylammonium bromide or N,N-dimethylformamide of 0.1M tetrabutylammonium iodide The reaction was carried out in N-dimethylformamide solvent. 12. The method according to any one of claims 1-3, wherein the ratio of the trifluoromethyl olefin compound, the alkyl electrophile and the solvent is 0.2-2 mmol: 1.2-1.5 equivalent: 2mL. 13. The method of claim 12, wherein the ratio of the trifluoromethyl olefin compound, the alkyl electrophile, and the solvent is 0.2 mmol: 1.5 equiv: 2 mL. 14. The method according to any one of claims 1-3, wherein the concentration of the reaction solution is 0.01-1 mol/L. 15. The method according to any one of claims 1-3, wherein the reaction temperature is 10-40°C. 16. The method of any one of claims 1-3, wherein the method reacts with the following reaction equation:

in

and R is as defined in any one of claims 1-3.

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