CN117049935B - Method for constructing carbon-carbon bond through electrophilic cross-coupling reaction - Google Patents

Method for constructing carbon-carbon bond through electrophilic cross-coupling reaction Download PDF

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CN117049935B
CN117049935B CN202311324291.5A CN202311324291A CN117049935B CN 117049935 B CN117049935 B CN 117049935B CN 202311324291 A CN202311324291 A CN 202311324291A CN 117049935 B CN117049935 B CN 117049935B
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CN117049935A (en
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祁伟
牟勇
邓小艳
祁生
吴逢伟
谭康利
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Gansu Taiyou Biotechnology Co ltd
Chengdu Taihe Weiye Biotechnology Co ltd
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Abstract

The invention discloses a method for constructing a carbon-carbon bond through electrophilic cross-coupling reaction, and belongs to the technical field of organic synthesis. The benzocyclohexenyl carboxamide compound shown in formula I and electrophile undergo electrophilic cross-coupling reaction under the action of a catalytic system to generate a compound containing carbon bonds shown in formula II. The invention firstly utilizes a catalytic system of organic alkali and boric acid ester to realize the technology of constructing C-C bond by electrophilic cross-coupling reaction of benzocyclohexenyl carbonamide compounds and electrophiles under the condition of nonmetal catalysis; solves the problems of high cost and the like of the traditional transition metal catalysis in the prior art, and the system provides new knowledge on the activation of the C-O bond.

Description

Method for constructing carbon-carbon bond through electrophilic cross-coupling reaction
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for constructing a carbon-carbon bond by electrophilic cross-coupling reaction.
Background
Before the field of inert carbon-oxygen bond activation arose, the coupling reaction to build c—c bonds (carbon-carbon bonds) had the following problems:
is limited to metal catalysis, especially to palladium, ruthenium, rhodium and other traditional noble metals.
However, with the development of chemistry, the requirements of green and sustainable are higher and higher, and the traditional noble metal catalysis also has the defects of environmental pollution, high cost and difficult post-treatment.
Based on the above, there is a need for an environmentally friendly, non-toxic, naturally abundant, economical electrophile to replace noble metals to realize the construction of c—c bonds.
Disclosure of Invention
In order to solve the problem that the construction of the existing C-C bond is limited to a noble metal catalyst, the invention aims to provide a method for constructing a carbon-carbon bond by electrophilic cross-coupling reaction.
The technical scheme for solving the technical problems is as follows:
a method for constructing carbon-carbon bond by electrophilic cross-coupling reaction comprises the steps of carrying out electrophilic cross-coupling reaction on a benzocyclohexenyl carboxamide compound shown in a formula I and an electrophilic reagent under the action of a catalytic system to generate a compound containing carbon-carbon bond shown in a formula II;
wherein the catalytic system comprises an organic strong base and boric acid ester; the structural formula of the formula I isThe structural formula of the formula II is +.>；
R 1 Is any one of hydrogen, alkyl, halogen, olefin, aryl, amide, amino, ether and mercapto, R 2 Is primary alkyl or secondary alkyl;
the method for constructing the carbon-carbon bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, placing boric acid ester in a reactor and introducing protective gas;
step 2, sequentially adding a benzocyclohexenyl carboxamide compound, dropwise adding an electrophile, adding a solvent and organic strong base into a reactor, and heating to perform electrophilic cross-coupling reaction to generate a carbon bond-containing compound; wherein the solvent is benzotrifluoride.
Based on the technical scheme, the invention can also be improved as follows:
further, R 1 Is hydrogen, alkyl with 1-20 carbon atoms, halogen,And->Any one of them;
R 2 is a primary alkyl group having 1 to 15 carbon atoms or a secondary alkyl group having 1 to 15 carbon atoms, R 3 Is an azacyclic or methyl group.
Further, the electrophile comprises alkoxyl phosphate shown in a formula III or haloalkane shown in a formula IV, wherein the structural formula of the formula III is R 2 -OPO(OPh) 2 The structural formula of the formula IV is R 2 -X; wherein R is 2 Is a primary alkyl group having 1 to 15 carbon atoms or a secondary alkyl group having 1 to 15 carbon atoms, and X is a halogen element. Further, X in formula IV is Br or Cl.
Further, the reaction conditions for electrophilic cross-coupling reactions are: and reacting for 8-16 hours at 40-60 ℃ in a protective gas atmosphere.
Further, the molar ratio of the benzocyclohexenyl carboxamide compound, the borate, the electrophile and the organic alkali is 0.2-1.0:0.2-1.5:0.2-1.5:0.6-4; preferably, the molar ratio of benzocyclohexenyl carboxamide compound, borate, electrophile, and organic strong base is 0.2:0.26:0.24:0.8.
Further, the borate is pinacol diboronate, the organic strong base is sodium bis (trimethylsilyl) amide, and the shielding gas is nitrogen.
The invention has the following beneficial effects:
1. the invention firstly utilizes a catalytic system consisting of organic alkali and boric acid ester to realize the technology of constructing C-C bond by electrophilic cross-coupling reaction of benzocyclohexenyl carbonamide compounds and electrophiles (including oxy electrophiles or halogenated hydrocarbon electrophiles) under the condition of nonmetal catalysis.
In the invention, a system consisting of organic alkali and boric acid ester enables cations to coordinate and activate C-O bonds (carbon-oxygen bonds) to reduce LUMO (highest occupied molecular orbital), and anions to increase HOMO (lowest unoccupied molecular orbital) of boron; in addition, sodium bis (trimethylsilyl) amide (NaHMDS) as the organic strong base, naHMDS contains stronger cage radical character and can activate this process.
Based on the above, the invention solves the problems of environmental pollution, high cost and the like existing in the prior art using the traditional transition metal catalysis by utilizing a system of organic strong base and boric acid ester, and the system provides new knowledge on the activation of C-O bonds.
2. The invention uses the system of organic strong alkali and boric acid ester to activate inert C-O bond, which is a perfect substitute for metal catalyst. And the technology of constructing the C-C bond by utilizing the benzocyclohexenyl carbonamide compound and the electrophile (comprising the oxo electrophile or the halohydrocarbon electrophile) to carry out electrophilic cross-coupling reaction solves the problems of environmental pollution, high cost and the like existing in the prior art of using the traditional transition metal catalysis.
Meanwhile, raw materials of the benzocyclohexenyl carboxamide and alkoxyl phosphate oxo electrophile are ubiquitous in natural products, and the synthesis method is simple in step, low in raw material price and easy to obtain. By utilizing the method, the C-C bond is constructed efficiently, and the natural product can be applied and reformed, so that the reaction has a very good application prospect.
Based on the above, in the research of exploring the activation of C-O bonds, we propose that a metal-free catalytic system activates inert C-O bonds, which accords with the concept of green chemistry better, so that the reaction system is simpler and can be converted into a target product with high efficiency.
Drawings
FIG. 1 is a hydrogen spectrum of the compounds prepared in example 2, example 6 and example 9 of the present invention;
FIG. 2 is a graph showing the carbon spectrum of the compounds prepared in example 2, example 6 and example 9 of the present invention;
FIG. 3 is a hydrogen spectrum of the compounds prepared in example 3, example 7 and example 10 of the present invention;
FIG. 4 is a graph showing the carbon spectrum of the compounds prepared in examples 3, 7 and 10 according to the present invention;
FIG. 5 is a hydrogen spectrum of the compounds prepared in example 4, example 8 and example 11 of the present invention;
FIG. 6 is a graph showing the carbon spectrum of the compounds prepared in examples 4, 8 and 11 according to the present invention;
FIG. 7 is a hydrogen spectrum of the compound prepared in example 5 of the present invention;
FIG. 8 is a carbon spectrum of the compound prepared in example 5 of the present invention;
FIG. 9 is a hydrogen spectrum of the compound prepared in example 12 of the present invention;
FIG. 10 is a carbon spectrum of the compound prepared in example 12 of the present invention;
FIG. 11 is a hydrogen spectrum of the compound prepared in example 13 of the present invention;
FIG. 12 is a carbon spectrum of the compound prepared in example 13 of the present invention;
FIG. 13 is a hydrogen spectrum of the compound prepared in example 14 of the present invention;
FIG. 14 is a carbon spectrum of the compound prepared in example 14 of the present invention;
FIG. 15 is a hydrogen spectrum of the compound prepared in example 15 of the present invention;
FIG. 16 is a carbon spectrum of the compound prepared in example 15 of the present invention;
FIG. 17 is a hydrogen spectrum of the compound prepared in example 16 of the present invention;
FIG. 18 is a carbon spectrum of a compound prepared in example 16 of the present invention;
FIG. 19 is a hydrogen spectrum of the compound prepared in example 17 of the present invention;
FIG. 20 is a carbon spectrum of the compound prepared in example 17 of the present invention.
Detailed Description
The principles and features of the present invention are described below with reference to the drawings, the examples are illustrated for the purpose of illustrating the invention and are not to be construed as limiting the scope of the invention. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1
The preparation of the phenyl diethyl carbamate comprises the following steps:
step C1, selecting a 50mL round-bottom flask, adding a magnet, plugging a rubber plug, plugging a balloon, pumping nitrogen, and filling nitrogen into the round-bottom flask;
step C2, 10g of phenylpropenone and 1.5M dry tetrahydrofuran were charged into a round bottom flask, and then the reactor was placed under-20℃to allow the phenylpropenone to dissolve in the tetrahydrofuran.
Step C3, continuously dropwise adding 1.1 equivalent of hexamethyldisilazane potassium amide (KHMDS) into the round-bottom flask, wherein the adding time is 15-30 minutes, and stirring for 1h after adding; in this example KHMDS was dissolved in Tetrahydrofuran (THF) to form a 1mmol/mL KHMDS solution, which was then added dropwise to a round bottom flask.
Step C4, continuously dropwise adding 1.2 equivalents of diethyl carbamoyl chloride into the round-bottomed flask for 15-30 minutes; then the temperature is raised to 0 ℃ and stirred for 30min, and finally the reaction is stirred for 16h after being raised to room temperature.
Step C5, quenching the reaction in the step C4 by using saturated sodium bicarbonate solution, and then adding ethyl acetate for extraction and washing by using saturated saline; the obtained organic phase was dried over anhydrous sodium sulfate, dried in vacuo, and purified by column chromatography (PE/ea=10/1) to give phenyl diethyl carbamate (1.95 g-2.44g, yield 60% -75%) as a colorless oily liquid.
The dry tetrahydrofuran in this example was obtained by subjecting tetrahydrofuran to a pre-drying treatment with sodium.
The preparation of the cyclopentyl diphenyl phosphate specifically comprises the following steps:
step B1, selecting a 25mL round-bottom flask, adding a magnet, plugging a rubber plug, inserting a balloon, sequentially injecting 10mmol of cyclopentanol, 10mL of tetrahydrofuran, 1.5 equivalent of triethylamine and 1.0 equivalent of N-methylimidazole into the round-bottom flask, placing the round-bottom flask in an environment with the temperature of 0 ℃, continuously dropwise adding 1.5 equivalent of diphenyl chlorophosphate, and stirring for 30min; after stirring, the round-bottomed flask was left to react at room temperature with stirring for 16h.
Step B2, quenching the reaction in the step B1 by using saturated sodium bicarbonate solution, and then adding ethyl acetate for extraction and washing by using saturated saline; finally, the obtained organic phase is dried by anhydrous sodium sulfate and then is dried in vacuum; after that, the mixture was purified by column chromatography (PE/ea=5/1) to obtain diphenyl cyclopentyl phosphate as a colorless oily liquid.
Example 2
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding magnetons into a reactor, and adding 0.26mmol of pinacol diboronate (B) into the reactor 2 pin 2 ) The rubber stopper is plugged, the nitrogen ball is plugged, and the nitrogen is replaced three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in example 1, 0.24mmol of the diphenyl cyclopentyl phosphate prepared in example 1, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence under a nitrogen atmosphere, and heating to 40 ℃ under the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and in fig. 1 and 2;
1 H NMR (400 MHz, CDCl 3 ) δ 7.35 (d, J = 7.6 Hz, 1 H), 7.24-7.20 (m, 1 H), 7.16-7.13 (m, 2 H), 5.93 (t, J = 4.4 Hz, 1 H), 3.02 (m, 1 H), 2.73 (t, J = 7.9 Hz, 2 H), 2.26 (q, J = 7.9 Hz, 2 H), 2.04-1.99 (m, 2 H), 1.81-1.73 (m, 2 H), 1.71-1.64 (m, 2 H), 1.53-1.46 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 140.1, 136.9, 135.8, 127.4, 126.3, 126.2, 123.1, 121.5, 41.1, 32.1, 28.5, 24.9, 23.2。
as can be seen in connection with fig. 1 and 2, this example successfully synthesizes a carbon bond-containing compound.
Example 3
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylcarbamate prepared in the example 1, 0.24mmol of diphenyl cyclohexylphosphate, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased from the reagent company, naHMDS is dispersed in THF to form a mixture having a concentration of 2.0M, and the mixture is fed into the reactor, and the preparation method of diphenyl cyclohexyl phosphate is the same as that of diphenyl cyclopentyl phosphate in example 1, except that cyclopentanol in step B1 is replaced with cyclohexanol.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 3 and 4;
1 H NMR (400 MHz, CDCl 3 ) δ 7.30 (d,J= 7.7 Hz, 1 H), 7.22-7.19 (m, 1 H), 7.14-7.11 (m, 2 H), 5.86 (t,J= 4.8 Hz, 1 H), 2.70 (t,J= 7.9 Hz, 2 H), 2.53 (m, 1 H), 2.24 (td,J= 8.0, 4.8 Hz, 2H), 1.98-1.88 (m, 2 H), 1.88-1.70 (m, 3 H), 1.50-1.35 (m, 2 H), 1.33-1.17 (m, 3 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 141.8, 137.1, 135.0, 127.6, 126.2, 126.2, 122.2, 121.9, 38.7, 33.1, 28.6, 27.1, 26.7, 23.1。
as can be seen in conjunction with fig. 3 and 4, this example successfully synthesizes a carbon bond-containing compound.
Example 4
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 0.24mmol of diphenyl cyclobutyl phosphate, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence under a nitrogen atmosphere, and heating to 40 ℃ under the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased by reagent company, and NaHMDS is dispersed in THF to form a mixture with the concentration of 2.0M, and the mixture is added into a reactor; the preparation of diphenyl cyclobutyl phosphate was identical to that of diphenyl cyclopentyl phosphate in example 1, except that cyclopentanol in step B1 was replaced by cyclobutyl alcohol.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 5 and 6;
1 H NMR (400 MHz, CDCl 3 ) δ 7.20-7.10 (m, 4 H), 5.84 (td,J= 4.8 Hz, 1.9 Hz, 1 H), 3.50-3.38 (m, 1 H), 2.74 (t,J= 8.0 Hz, 2 H), 2.32-2.23 (m, 4 H), 2.10-1.94 (m, 3H)，1.89-1.68 (m, 1 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 140.0, 136.7, 134.6, 127.5, 126.4, 126.2, 123.0, 122.2, 37.5, 28.3, 28.1, 23.1, 18.3。
as can be seen in conjunction with fig. 5 and 6, this example successfully synthesizes a carbon bond-containing compound.
Example 5
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylcarbamate prepared in the example 1, 0.24mmol of diphenyl isopropyl phosphate, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased by reagent company, and NaHMDS is dispersed in THF to form a mixture with the concentration of 2.0M, and the mixture is added into a reactor; the preparation of diphenyl isopropyl phosphate was the same as that of cyclopentyl diphenyl phosphate in example 1, except that cyclopentanol in step B1 was replaced with isopropyl alcohol.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 7 and 8;
1 H NMR (400 MHz, CDCl 3 ) δ 7.33 (d, 1 H), 7.24-7.20 (m, 1 H), 7.16-7.12 (m, 2 H), 5.91 (s, 1 H), 3.00-2.93 (m, 1 H), 2.72 (t,J= 7.9 Hz, 2 H), 2.26 (q,J= 7.9 Hz, 2 H), 1.18 (d,J= 6.8 Hz, 6 H)；
13 C NMR (100 MHz, CDCl 3 )δ 142.7, 137.1, 135.1, 127.6, 126.3, 126.2, 122.5, 121.4, 28.6, 28.2, 23.1, 22.3。
as can be seen in conjunction with fig. 7 and 8, this example successfully synthesizes a carbon bond-containing compound.
Example 6
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.2mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 0.2mmol of cyclopentyl bromide as an electrophile, 1.0mL of benzotrifluoride and 0.6mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the carbon-carbon bond-containing compound. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and in fig. 1 and 2;
1 H NMR (400 MHz, CDCl 3 ) δ 7.35 (d, J = 7.6 Hz, 1 H), 7.24-7.20 (m, 1 H), 7.16-7.13 (m, 2 H), 5.93 (t, J = 4.4 Hz, 1 H), 3.02 (m, 1 H), 2.73 (t, J = 7.9 Hz, 2 H), 2.26 (q, J = 7.9 Hz, 2 H), 2.04-1.99 (m, 2 H), 1.81-1.73 (m, 2 H), 1.71-1.64 (m, 2 H), 1.53-1.46 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 140.1, 136.9, 135.8, 127.4, 126.3, 126.2, 123.1, 121.5, 41.1, 32.1, 28.5, 24.9, 23.2。
as can be seen in connection with fig. 1 and 2, this example successfully synthesizes a carbon bond-containing compound.
Example 7
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 1.5mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 1.0mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 1.5mmol of cyclohexyl bromide as an electrophile, 1.0mL of benzotrifluoride and 4mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 3 and 4;
1 H NMR (400 MHz, CDCl 3 ) δ 7.30 (d,J= 7.7 Hz, 1 H), 7.22-7.19 (m, 1 H), 7.14-7.11 (m, 2 H), 5.86 (t,J= 4.8 Hz, 1 H), 2.70 (t,J= 7.9 Hz, 2 H), 2.53 (m, 1 H), 2.24 (td,J= 8.0, 4.8 Hz, 2H), 1.98-1.88 (m, 2 H), 1.88-1.70 (m, 3 H), 1.50-1.35 (m, 2 H), 1.33-1.17 (m, 3 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 141.8, 137.1, 135.0, 127.6, 126.2, 126.2, 122.2, 121.9, 38.7, 33.1, 28.6, 27.1, 26.7, 23.1。
as can be seen in conjunction with fig. 3 and 4, this example successfully synthesizes a carbon bond-containing compound.
Example 8
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 0.24mmol of cyclobutyl bromide, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) serving as electrophiles into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the carbon-carbon bond-containing compound. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 5 and 6;
1 H NMR (400 MHz, CDCl 3 ) δ 7.20-7.10 (m, 4 H), 5.84 (td,J= 4.8 Hz, 1.9 Hz, 1 H), 3.50-3.38 (m, 1 H), 2.74 (t,J= 8.0 Hz, 2 H), 2.32-2.23 (m, 4 H), 2.10-1.94 (m, 3H)，1.89-1.68 (m, 1 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 140.0, 136.7, 134.6, 127.5, 126.4, 126.2, 123.0, 122.2, 37.5, 28.3, 28.1, 23.1, 18.3。
as can be seen in conjunction with fig. 5 and 6, this example successfully synthesizes a carbon bond-containing compound.
Example 9
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 0.24mmol of cyclopentyl chloride as an electrophile, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and in fig. 1 and 2;
1 H NMR (400 MHz, CDCl 3 ) δ 7.35 (d, J = 7.6 Hz, 1 H), 7.24-7.20 (m, 1 H), 7.16-7.13 (m, 2 H), 5.93 (t, J = 4.4 Hz, 1 H), 3.02 (m, 1 H), 2.73 (t, J = 7.9 Hz, 2 H), 2.26 (q, J = 7.9 Hz, 2 H), 2.04-1.99 (m, 2 H), 1.81-1.73 (m, 2 H), 1.71-1.64 (m, 2 H), 1.53-1.46 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 140.1, 136.9, 135.8, 127.4, 126.3, 126.2, 123.1, 121.5, 41.1, 32.1, 28.5, 24.9, 23.2。
as can be seen in connection with fig. 1 and 2, this example successfully synthesizes a carbon bond-containing compound.
Example 10
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 0.24mmol of cyclohexyl chloride as an electrophile, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 50 ℃ in the nitrogen protection atmosphere to react for 12 hours to obtain the compound containing carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 3 and 4;
1 H NMR (400 MHz, CDCl 3 ) δ 7.30 (d,J= 7.7 Hz, 1 H), 7.22-7.19 (m, 1 H), 7.14-7.11 (m, 2 H), 5.86 (t,J= 4.8 Hz, 1 H), 2.70 (t,J= 7.9 Hz, 2 H), 2.53 (m, 1 H), 2.24 (td,J= 8.0, 4.8 Hz, 2H), 1.98-1.88 (m, 2 H), 1.88-1.70 (m, 3 H), 1.50-1.35 (m, 2 H), 1.33-1.17 (m, 3 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 141.8, 137.1, 135.0, 127.6, 126.2, 126.2, 122.2, 121.9, 38.7, 33.1, 28.6, 27.1, 26.7, 23.1。
as can be seen in conjunction with fig. 3 and 4, this example successfully synthesizes a carbon bond-containing compound.
Example 11
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of the phenyl propyl diethylaminocarbamate prepared in the example 1, 0.24mmol of cyclobutyl chloride, 1.0mL of benzotrifluoride and 0.8mmol of sodium bis (trimethylsilyl) amide (NaHMDS) serving as electrophiles into a reactor in sequence in a nitrogen atmosphere, and heating to 60 ℃ in the nitrogen protection atmosphere to react for 8 hours to obtain the carbon-carbon bond-containing compound. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THF to form a mixture with a concentration of 2.0M, which is added to the reactor.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 5 and 6;
1 H NMR (400 MHz, CDCl 3 ) δ 7.20-7.10 (m, 4 H), 5.84 (td,J= 4.8 Hz, 1.9 Hz, 1 H), 3.50-3.38 (m, 1 H), 2.74 (t,J= 8.0 Hz, 2 H), 2.32-2.23 (m, 4 H), 2.10-1.94 (m, 3H)，1.89-1.68 (m, 1 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 140.0, 136.7, 134.6, 127.5, 126.4, 126.2, 123.0, 122.2, 37.5, 28.3, 28.1, 23.1, 18.3。
as can be seen in conjunction with fig. 5 and 6, this example successfully synthesizes a carbon bond-containing compound.
Example 12
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of 7-methyl-3, 4-dihydronaphthalene-1-yl diethyl carbamate, 0.24mmol of cyclopentyl diphenyl phosphate prepared in the example 1, 1.0mL of benzotrifluoride and 0.8mmol of bis (trimethylsilyl) sodium amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon-carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased by reagent company, and NaHMDS is dispersed in THF to form a mixture with the concentration of 2.0M, and the mixture is added into a reactor; the preparation method of 7-methyl-3, 4-dihydronaphthalen-1-yl diethylamino formate in this example was the same as that of the phenylpropenyl diethylamino formate in example 1, except that phenylpropenyl ketone was replaced with (E) -1- (m-tolyl) but-2-en-1-one.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 9 and 10;
1 H NMR (400 MHz, CDCl 3 ) δ 7.15 (s, 1 H), 7.04 (d,J= 7.5 Hz, 1H), 6.95 (d,J= 7.5 Hz, 1H), 5.90 (t,J= 4.4 Hz, 1 H), 2.99 (p,J= 8.1 Hz, 1H), 2.67 (t,J= 7.9 Hz, 2 H), 2.35 (s, 3 H), 2.22 (q,J= 7.9 Hz, 3 H), 2.04-1.93 (m, 2 H), 1.78-1.62 (m, 4 H), 1.53- 1.40 (m, 2H)；
13 C NMR (100 MHz, CDCl 3 )δ 140.1, 135.6, 135.5, 133.9, 127.3, 126.8, 123.9, 121.6, 41.0, 32.1, 28.1, 24.9, 23.4, 21.5。
as can be seen in conjunction with fig. 9 and 10, this example successfully synthesizes a carbon bond-containing compound.
Example 13
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of 7-methoxy-3, 4-dihydronaphthalene-1-yl diethyl carbamate shown in a reaction formula, 0.24mmol of cyclopentyl diphenyl phosphate prepared in example 1, 1.0mL of benzotrifluoride and 0.8mmol of bis (trimethylsilyl) sodium amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16h to obtain the compound containing carbon-carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased by reagent company, and NaHMDS is dispersed in THF to form a mixture with the concentration of 2.0M, and the mixture is added into a reactor; the preparation method of 7-methoxy-3, 4-dihydronaphthalen-1-yl diethylamino formate in this example was the same as that of the phenylpropenyl diethylamino formate in example 1, except that phenylpropenyl ketone was replaced with (E) -1- (3-methoxyphenyl) but-2-en-1-one.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 11 and 12;
1 H NMR (400 MHz, CDCl 3 ) δ 7.05 (d,J= 8.1 Hz, 1 H), 6.91 (d,J= 2.3 Hz, 1 H), 6.67 (dd,J= 8.2, 2.6 Hz, 1 H), 5.92 (t,J= 4.1 Hz, 1 H), 3.80 (s, 3 H), 2.94 (p,J= 7.7 Hz, 1 H), 2.63 (t,J= 7.8 Hz, 2 H), 2.27-2.16 (m, 2 H), 2.03-1.92 (m, 2 H), 1.79-1.61 (m, 4 H), 1.52-1.39 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 )δ 158.2, 140.0, 136.9, 129.2, 127.9, 122.3, 110.4, 110.2, 55.4, 41.1, 32.1, 27.6, 24.9, 23.5。
as can be seen in conjunction with fig. 11 and 12, this example successfully synthesizes a carbon bond-containing compound.
Example 14
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of 7- (pyridine-2-oxy) -3, 4-dihydronaphthalene-1-yl diethyl carbamate, 0.24mmol of cyclopentyl diphenyl phosphate prepared in example 1, 1.0mL of benzotrifluoride and 0.8mmol of bis (trimethylsilyl) sodium amide (NaHMDS) into a reactor in sequence under a nitrogen atmosphere, and heating to 40 ℃ under the nitrogen atmosphere to react for 16h to obtain the compound containing carbon-carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased by reagent company, and NaHMDS is dispersed in THF to form a mixture with the concentration of 2.0M, and the mixture is added into a reactor; the preparation method of 7- (pyridin-2-yloxy) -3, 4-dihydronaphthalen-1-yl diethylamino formate in this example was the same as that of phenylpropenyl diethylamino formate in example 1, except that phenylpropenone was replaced with 7- (pyridin-2-yl) -3, 4-dihydronaphthalen-1 (2H) -one; wherein, the reaction formula of the 7- (pyridine-2-yl) -3, 4-dihydronaphthalene-1 (2H) -ketone is as follows:the preparation method comprises the following steps:
step 1, adding a magneton into a reactor, adding cuprous bromide (0.1 mmol), cesium carbonate (2 mmol) and 6-hydroxy-1-tetralone (1.2 mmol) into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping nitrogen three times.
Step 2, adding 2-bromopyridine (1 mmol), 1- (2-pyridyl) propan-2-one (0.2 mmol) and DMSO (1.5 mL) into a reactor by a syringe in sequence under nitrogen atmosphere, heating to 90 ℃ under nitrogen protection atmosphere for reaction for 8h, cooling to room temperature, and usingDiluting with ethyl acetate (10 mL), filtering to remove inorganic salt, vacuum concentrating to remove solvent, and purifying by column chromatography to obtain 7- (pyridin-2-yl) -3, 4-dihydronaphthalen-1 (2H) -one;
the compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 13 and 14;
1 H NMR (400 MHz, CDCl 3 ) δ 8.20 (d,J= 4.3 Hz, 1 H), 7.65 (t,J= 7.0 Hz, 1 H), 7.14 (d,J= 8.0 Hz, 1 H), 7.09 (s, 1 H), 6.99-6.93 (m, 1 H), 6.88 (t,J= 8.6 Hz, 2 H), 5.92 (t,J= 4.4 Hz, 1 H), 2.87 (p,J= 8.0 Hz, 1 H), 2.69 (t,J= 7.9 Hz, 2 H), 2.25 (q,J= 7.7 Hz, 2 H), 1.99-1.86 (m, 2 H), 1.75-1.55 (m, 4 H), 1.49-1.40 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 )δ 164.2, 152.4, 147.8, 139.8, 139.3, 137.4, 133.3, 128.3, 122.2, 118.8, 118.1, 116.5, 111.0, 41.1, 31.9, 27.9, 24.8, 23.3。
as can be seen in conjunction with fig. 13 and 14, this example successfully synthesizes a carbon bond-containing compound.
Example 15
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of 7-fluoro-3, 4-dihydronaphthalene-1-yl diethyl carbamate, 0.24mmol of cyclopentyl diphenyl phosphate prepared in the example 1, 1.0mL of benzotrifluoride and 0.8mmol of bis (trimethylsilyl) sodium amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon-carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased from reagent company, and NaHMDS is dispersed in THFAdding the mixture with the concentration of 2.0M into a reactor; the preparation method of 7-fluoro-3, 4-dihydronaphthalen-1-yl diethylamino formate in this example was the same as that of the phenylpropenyl diethylamino formate in example 1, except that phenylpropenyl ketone was replaced with (E) -1- (3-fluorophenyl) but-2-en-1-one.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 15 and 16;
1 H NMR (400 MHz, CDCl 3 ) δ 7.09-7.04 (m, 2 H), 7.01 (dd,J= 10.9, 2.7 Hz, 1H), 6.80 (td,J= 8.4, 2.7 Hz, 1H), 5.95 (t,J= 4.7 Hz, 1 H), 2.98-2.78 (m, 1 H), 2.65 (t,J= 7.9 Hz, 2 H), 2.38-2.11 (m, 2 H), 1.96 (dq,J= 10.8, 6.4, 5.9 Hz, 2 H), 1.78-1.62 (m, 4 H), 1.51-1.35 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 163.0, 160.6, 139.6, 137.7, 137.6, 132.2, 128.3, 128.2, 122.8, 112.4, 112.2, 110.4, 110.1.41.1, 31.9, 29.7, 27.6, 24.9, 23.3。
as can be seen in conjunction with fig. 15 and 16, this example successfully synthesizes a carbon bond-containing compound.
Example 16
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of 7-chloro-3, 4-dihydronaphthalene-1-yl diethyl carbamate, 0.24mmol of cyclopentyl diphenyl phosphate prepared in the example 1, 1.0mL of benzotrifluoride and 0.8mmol of bis (trimethylsilyl) sodium amide (NaHMDS) into a reactor in sequence in a nitrogen atmosphere, and heating to 40 ℃ in the nitrogen protection atmosphere to react for 16 hours to obtain the compound containing carbon-carbon bonds. Which is a kind ofIn which benzotrifluoride is an ultra-dry solvent purchased from the reagent company and NaHMDS is dispersed in THF to form a mixture having a concentration of 2.0M and is fed into the reactor. The preparation method of 7-chloro-3, 4-dihydronaphthalen-1-yl diethylaminoformate in this example was the same as that of the phenylpropenyl diethylaminoformate in example 1, except that phenylpropenone was replaced with (E) -1- (3-chlorophenyl) but-2-en-1-one.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 17 and 18;
1 H NMR (400 MHz, CDCl 3 ) δ 7.27 (s, 1 H), 7.09-7.04 (m, 2 H), 5.94 (t,J= 4.4 Hz, 1 H), 2.91 (p,J= 8.1 Hz, 1 H), 2.65 (t,J= 7.9 Hz, 2 H), 2.22 (q,J= 7.9 Hz, 2 H), 1.98 (dd,J= 11.0, 6.5 Hz, 2 H), 1.77-1.60 (m, 4 H), 1.52-1.38 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 139.4, 137.5, 135.1, 131.9, 128.5, 125.9, 123.3, 122.8, 40.9, 32.0, 27.8, 24.9, 23.1。
as can be seen in conjunction with fig. 17 and 18, this example successfully synthesizes a carbon bond-containing compound.
Example 17
A method for constructing C-C bond by electrophilic cross-coupling reaction specifically comprises the following steps:
step 1, adding a magneton into a reactor, adding 0.26mmol of bisboronic acid pinacol ester into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping and replacing nitrogen three times.
Step 2, adding 0.2mmol of 7-morpholino-3, 4-dihydronaphthalene-1-yl diethyl carbamate, 0.24mmol of cyclopentyl diphenyl phosphate prepared in dropping example 1, 1.0mL of benzotrifluoride and 0.8mmol of bis (trimethylsilyl) sodium amide (NaHMDS) into a reactor in sequence under nitrogen atmosphere, heating to 40 ℃ under nitrogen protection atmosphere for reacting for 16 hours to obtain the compound containing carbon-carbon bonds. Wherein benzotrifluoride is an ultra-dry solvent purchased by reagent company, and NaHMDS is dispersed in THF to form a mixture with the concentration of 2.0M, and the mixture is added into a reactor; the preparation method of 7-morpholino-3, 4-dihydronaphthalen-1-yl diethylaminoformate in this example is the same as that of the phenylpropenyl diethylaminoformate in example 1, except that phenylpropenone is replaced with 7-morpholino-3, 4-dihydronaphthalen-1 (2H) -one, wherein the 7-morpholino-3, 4-dihydronaphthalen-1 (2H) -one is prepared according to the following reaction scheme:the preparation method comprises the following steps:
step 1, adding magnetons into a reactor, adding palladium acetate (0.01 mmol), ruPhos (0.02 mmol), 7-bromo-3, 4-dihydro-2H-1-naphthalenone (1.05 mmol) and powdery sodium n-butoxide (1.2 mmol) into the reactor, plugging a rubber plug, plugging a nitrogen ball, and pumping nitrogen three times.
Step 2, morpholine (1.0 mmol) was added to the reactor by syringe under nitrogen atmosphere, heated to 110 ℃ under nitrogen protection atmosphere, reacted for 12h, cooled to room temperature, and reacted with dichloromethane: diluting the mixed solvent of water (1:1), separating liquid, collecting organic phase, vacuum concentrating to remove solvent, and purifying by column chromatography to obtain 7-morpholine-3, 4-dihydronaphthalene-1 (2H) -one.
The compound prepared in this example was subjected to hydrogen spectroscopy 1 H NMR) and carbon spectrum [ ] 13 C NMR) analysis, the results are described in detail below and fig. 19 and 20;
1 H NMR (400 MHz, CDCl 3 ) δ 7.05 (d,J= 8.1 Hz, 1 H), 6.93 (d,J= 2.5 Hz, 1 H), 6.71 (dd,J= 8.1, 2.5 Hz, 1 H), 5.91 (t,J= 4.1 Hz, 1 H), 3.93-3.76 (m, 4 H), 3.17-3.08 (m, 4 H), 2.96 (p,J= 8.1 Hz, 1 H), 2.62 (t,J= 7.8 Hz, 2 H), 2.21 (q,J= 7.4 Hz, 2 H), 2.01-1.91 (m, 2 H), 1.80-1.63 (m, 4 H), 1.54-1.43 (m, 2 H)；
13 C NMR (100 MHz, CDCl 3 ) δ 150.1, 140.1, 136.3, 129.2, 127.8, 122.1, 114.0, 112.1, 67.0, 50.3, 41.1, 32.1, 27.6, 25.0, 23.5。
as can be seen in conjunction with fig. 19 and 20, this example successfully synthesizes a carbon bond-containing compound.

Claims (5)

1. A method for constructing carbon-carbon bonds by electrophilic cross-coupling reaction is characterized in that,
the benzocyclohexenyl carboxamide compound shown in formula I and electrophilic reagent undergo electrophilic cross-coupling reaction under the action of a catalytic system to generate a compound shown in formula II and containing carbon bonds;
wherein the catalytic system comprises an organic strong base and a borate; the structural formula of the formula I isThe structural formula of the formula II is +.>；
The R is 1 Is hydrogen, halogen, methyl,、/>And->Any one of them; the R is 2 Is any one of cyclopentyl, cyclohexyl, cyclobutyl and isopropyl;
the electrophile comprises alkoxyl phosphate shown in a formula III or alkyl halide shown in a formula IV, wherein the structural formula of the formula III is R 2 -OPO(OPh) 2 The structural formula of the formula IV is R 2 -X; x is halogen element;
the boric acid ester is pinacol ester of biboronate, and the organic strong base is sodium bis (trimethylsilyl) amide.
2. The method of claim 1, wherein X in formula iv is Br or Cl.
3. The method of claim 1, wherein the electrophilic cross-coupling reaction is performed under reaction conditions of: and reacting for 8-16 hours at 40-60 ℃ in a protective gas atmosphere.
4. The method according to claim 1, wherein the molar ratio of the benzocyclohexenylcarboxamide compound, the borate, the electrophile and the organic strong base is 0.2-1.0:0.2-1.5:0.2-1.5:0.6-4.
5. A method according to claim 3, wherein the shielding gas is nitrogen.
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