A method for synthesizing 1,1-bisaryl compounds using non-activated alkenes

Abstract

The application relates to a method for synthesizing 1,1-bisaryl compounds by using non-activated alkenes, and belongs to the fields of organic synthesis methods and electrochemical catalysis. The application solves the technical problem that the existing reaction technology cannot realize efficient coupling of non-activated alkenes and halogenated arenes to generate 1,1-bisaryl compound products. In the application, a nickel catalyst is reduced on a cathode by a constant current under an inert gas atmosphere, then a secondary oxidative addition is carried out with another halogenated arene, and finally a 1,1-bisaryl compound product is generated through a reductive elimination step. The nickel catalyst circulates in the reaction by maintaining its valence state under electrochemical conditions, effectively avoiding the use of an additional chemical reducing agent, simplifying the operation and reducing the environmental burden. The reaction system of the application has high efficiency and universality, and can be applied to various halogenated arenes and non-activated alkenes under mild conditions, and has significant application value in the modification and synthesis of natural products and drug molecules.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of organic synthesis methods and electrochemical catalysis, and in particular to a method for 1,1-diarylation of unactivated olefins. BACKGROUND

[0002] Unactivated olefins are important building blocks in organic synthesis, playing a key role in the field of fine chemicals, drugs and functional materials, especially in drug systems containing 1,1-diaryl structures. The 1,1-diaryl structure plays a key role in its biological activity, for example, the antihistamine drug Chlorpheniramine is commonly used to relieve allergic symptoms such as rhinitis and urticaria.

[0003] 1,1-diarylation reaction is an important means of synthesizing polysubstituted aromatic compounds, and is widely used in the research and development of drugs, natural products and functional materials. However, existing researches are mostly focused on 1,2-diarylation, and there are few studies on 1,1-diarylation of unactivated olefins. Generally, 1,1-diarylation of olefins is challenging due to the difficulty in controlling selectivity and harsh reaction conditions. In addition, traditional methods usually require the use of highly active metal reagents or strong oxidizing agents, which limits the environmental friendliness and operational simplicity of the reaction. Therefore, it is of great significance to develop a green, efficient and simple method for 1,1-diarylation of unactivated olefins. SUMMARY

[0004] The present application solves the technical problem that existing reaction technologies cannot efficiently couple unactivated olefins and halogenated arenes to generate 1,1-diarylated products, and provides a 1,1-diarylation synthesis method based on electrochemical reduction of nickel catalysis.

[0005] The present application utilizes electrochemical means to reduce nickel catalyst to low-valence nickel(0) at the cathode under an inert gas atmosphere by constant current. The nickel species first undergoes oxidative addition with halogenated arenes to form nickel(II) species, and then adds to unactivated olefins to form aryl nickel compounds intermediates. Subsequently, nickel(I) species is formed by reduction at the cathode. Subsequently, it further undergoes secondary oxidative addition with another halogenated arene, and finally generates 1,1-diarylated products through a reduction elimination step, while forming nickel(I), and completing the catalytic cycle of the nickel catalyst through valence change. The nickel catalyst maintains its valence cycle through electrochemical conditions in the reaction, effectively avoiding the use of external chemical reducing agents, simplifying the operation and reducing the environmental burden. In addition, the reaction system of the present application has high efficiency and universality, and can be applied to various halogenated arenes and unactivated olefins under mild conditions, especially showing significant application value in the modification and synthesis of natural products and drug molecules.

[0006] A method for synthesizing 1,1-bis aryl compounds by using non-activated olefins, which is specifically carried out by the following method:

[0007] I. Put an anode electrode and a cathode electrode in a reaction bottle, and then add non-activated olefin compounds, halogenated aromatic hydrocarbons, electrolyte, nickel catalyst, ligand and base under N2 atmosphere, and then add super dry solvent, and seal the system;

[0008] The halogenated aromatic hydrocarbons are iodobenzene, 4-iodobenzoic acid methyl ester, p-fluoroiodobenzene, p-chloroiodobenzene, 4'-iodoacetophenone, 4-iodoanisole, 4-iodobenzonitrile, 3-iodobenzo[b]thiophene or ketoprofen;

[0009] The electrolyte is tetrabutylammonium bromide;

[0010] The base in step I is 2,6-dimethylpyridine;

[0011] II. Stir the sealed system in step I under constant current to obtain a crude product;

[0012] III. Remove the solvent from the crude product obtained in step II by reduced pressure distillation, and then separate and purify the product by thin layer chromatography, and the obtained product is the 1,1-bis aryl compound.

[0013] Further, the non-activated olefin compounds in step I are vinylboronic acid pinacol ester, trimethylvinylsilane, dimethylphenylvinylsilane, vinylcyclohexane, n-pentene, n-hexene, n-heptene, 4-phenyl-1-butene or ketoprofen butenyl ester.

[0014] Further, the super dry solvent in step I is super dry N,N-dimethylacetamide.

[0015] Further, the nickel catalyst in step I is ethylene glycol dimethyl ether nickel bromide.

[0016] Further, the ligand in step I is 6,6-dimethyl-2,2-bipyridine.

[0017] Further, the use amount ratio of the halogenated aromatic hydrocarbons to the super dry solvent is 0.2 mmol:3 mL; the use amount ratio of the non-activated olefin compounds to the super dry solvent is 0.3-0.4 mmol:3 mL; the use amount ratio of the nickel catalyst to the super dry solvent is 0.015 mmol:3 mL; the use amount ratio of the ligand to the super dry solvent is 0.018 mmol:3 mL; the use amount ratio of the electrolyte to the super dry solvent is 0.3 mmol:3 mL; and the use amount ratio of the base to the super dry solvent is 0.1 mmol:3 mL.

[0018] Further, the anode electrode in step I is an iron electrode, and the cathode electrode is a nickel electrode.

[0019] Further, the current of the step two control constant current is 1mA, the reaction temperature is 30-50 DEG C, and the continuous power-on time is 10 hours.

[0020] Further, the step two adopts TLC to monitor the reaction progress.

[0021] Further, the solvent used in the step three is mixed solvent of petroleum ether and ethyl acetate with the volume ratio of (5-50):1.

[0022] The reaction of the application is as follows:

[0023]

[0024] Wherein R is pinacol boronic acid, silane or alkyl.

[0025] The reaction mechanism of the application is as shown in the figure. Figure 3

[0026] Initially, the nickel complex is generated by electrochemical reduction to form Ni 0 species (A). This species undergoes oxidative addition with a halogenated aromatic (1) to form an aryl nickel intermediate (B). Subsequently, a non-activated olefin (2) inserts into the aryl nickel bond to form intermediate (C). Intermediate (C) then undergoes a fast β-hydrogen elimination and migratory insertion step to form a π-benzyl Ni II species (D). The π-benzyl intermediate (D) is further reduced at the cathode to form a Ni I species (E) which undergoes oxidative addition with another molecule of halogenated aromatic to form intermediate (F). Finally, intermediate (F) is released by reductive elimination to the target 1,1-biaryl product (3) and a Ni I species (G). This catalytic cycle is completed by further reduction of the Ni I species (G) back to the Ni0species (A).

[0027] The application has the following advantages:

[0028] Compared with the prior art, the application synthesizes 1,1-biaryl compounds by a simple, green and efficient method, and has the following advantages:

[0029] (1) The electrons provided by the current in the reaction system serve as a cheap and clean reducing agent, avoiding the use of an external reducing agent, and the reaction operation is simple and the conditions are mild.

[0030] (2) The non-activated olefin compound, halogenated aromatic compound, nickel catalyst, nitrogen ligand, base and super dry solvent used in the reaction system are simple, cheap and easy to obtain commercial compounds, and the iron and nickel electrodes used are also relatively cheap electrode sheets, so that the reaction system is simple and economical. ​

[0031] (3) The reaction system substrate has wide application range, and can synthesize various 1,1-bis aryl compounds. The reaction substrates include various types of polysubstituted halogenated aromatic hydrocarbon compounds, non-activated olefin compounds, small molecule olefin compounds, and natural product and drug molecule derivatives.

[0032] (4) The synthesized 1,1-bis aryl compound can be used in the field of medicine, and can be used as a key intermediate or a drug active ingredient to help the research and development of new drugs and improve the treatment effect. BRIEF DESCRIPTION OF DRAWINGS

[0033] Figure 1 is the 1,1-bis aryl compound (3-1) obtained in Example 1 1 H NMR spectrum;

[0034] Figure 2 is the 1,1-bis aryl compound (3-1) obtained in Example 1 13 C NMR spectrum;

[0035] Figure 3 is the reaction mechanism diagram of the application. DETAILED DESCRIPTION

[0036] Specific embodiment one: a method for synthesizing 1,1-bis aryl compounds by using non-activated olefins, which is specifically carried out as follows:

[0037] I. Put an anode electrode and a cathode electrode in a reaction bottle, and add non-activated olefin compounds, halogenated aromatic hydrocarbons, electrolytes, nickel catalysts, ligands and bases under N2 atmosphere, and then add super dry solvent, and seal the system;

[0038] The halogenated aromatic hydrocarbons are iodobenzene, 4-iodobenzoic acid methyl ester, p-fluoroiodobenzene, p-chloroiodobenzene, 4'-iodoacetophenone, 4-iodoanisole, 4-iodobenzonitrile, 3-iodobenzo[b]thiophene or ketoprofen;

[0039] The electrolyte is tetrabutylammonium bromide;

[0040] The base in step one is 2,6-dimethylpyridine;

[0041] II. Pass a constant current into the sealed system of step one to obtain a crude product by stirring;

[0042] III. Remove the solvent from the crude product obtained in step two by reduced pressure distillation, and then separate and purify by thin layer chromatography, and the obtained product is the 1,1-bis aryl compound.

[0043] Specific embodiment two: the difference between this embodiment and specific embodiment one is that the non-activated olefin compound in step one is vinyl boronic acid pinacol ester, trimethylvinylsilane, dimethylphenylvinylsilane, vinylcyclohexane, n-pentene, n-hexene, n-heptene, 4-phenyl-1-butene or ketoprofen butenyl ester. The others are the same as specific embodiment one.

[0044] Specific embodiment three: the difference between this embodiment and specific embodiment one or two is that the super dry solvent in step one is super dry N,N-dimethylacetamide. The others are the same as specific embodiment one or two.

[0045] Specific embodiment four: the difference between this embodiment and one of specific embodiments one to three is that the nickel catalyst in step one is ethylene glycol dimethyl ether nickel bromide. The others are the same as one of specific embodiments one to three.

[0046] Specific embodiment five: the difference between this embodiment and one of specific embodiments one to four is that the ligand in step one is 6,6-dimethyl-2,2-bipyridine. The others are the same as one of specific embodiments one to four.

[0047] Specific embodiment six: the difference between this embodiment and one of specific embodiments one to five is that the ratio of the amount of the halogenated aromatic compound to the super dry solvent in step one is 0.2 mmol:3 mL; the ratio of the amount of the non-activated olefin compound to the super dry solvent is 0.3-0.4 mmol:3 mL; the ratio of the amount of the nickel catalyst to the super dry solvent is 0.015 mmol:3 mL; the ratio of the amount of the ligand to the super dry solvent is 0.018 mmol:3 mL; the ratio of the amount of the electrolyte to the super dry solvent is 0.3 mmol:3 mL; the ratio of the amount of the base to the super dry solvent is 0.1 mmol:3 mL. The others are the same as one of specific embodiments one to five.

[0048] Specific embodiment seven: the difference between this embodiment and one of specific embodiments one to six is that the anode electrode in step one is an iron electrode and the cathode electrode is a nickel electrode. The others are the same as one of specific embodiments one to six.

[0049] Specific embodiment eight: the difference between this embodiment and one of specific embodiments one to seven is that the constant current in step two is 1 mA, the reaction temperature is 30-50°C, and the continuous power-on time is 10 hours. The others are the same as one of specific embodiments one to seven.

[0050] Specific embodiment nine: the difference between this embodiment and one of specific embodiments one to eight is that TLC is used to monitor the reaction progress in step two. The others are the same as one of specific embodiments one to eight.

[0051] Specific embodiment ten: different from one of the specific embodiments one to nine is that the solvent used in the thin layer chromatography separation and purification in step three is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of (5-50):1. The others are the same as one of the specific embodiments one to nine.

[0052] The content of the present application is not limited to the above-mentioned embodiments, and the combination of one or several specific embodiments can also achieve the purpose of the application.

[0053] Example 1:

[0054] The method of the present embodiment for synthesizing 1,1-bis aryl compounds by using non-activated alkenes is specifically carried out as follows:

[0055] I. In a dry 8 mL reaction vial (equipped with a magnetic stirrer, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 0.3 mmol of vinyl boronic acid pinacol ester, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine are added, 3.0 mL of super dry DMA is added as solvent, and the system is protected by inert gas and sealed;

[0056] II. The sealed system of step I is stirred at room temperature, a constant current of 1 mA is continuously supplied, and the reaction is carried out for 10 h to obtain a crude product;

[0057] III. The crude product obtained in step II is extracted, dried, and the solvent is removed by reduced pressure distillation, and then thin layer chromatography separation and purification are carried out to obtain the product, which is identified as 1,1-bis aryl compound (3-1) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0058]

[0059] The purity is 99% and the yield is 77%; the nuclear magnetic data analysis is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.29-7.21 (m, 10H), 7.16-7.10 (m, 2H), 4.28 (t, J = 8.5 Hz, 1H), 1.60 (d, J = 8.5 Hz, 2H), 1.05 (s, 12H).

[0060] 13 C NMR (101 MHz, CDCl3) δ 146.64, 128.30, 127.74, 125.97, 83.19, 46.58, 24.63.

[0061] Example 2:

[0062] The method for synthesizing 1,1-bis aryl compounds by using non-activated olefins in the embodiment is specifically carried out in the following manner:

[0063] I. In a dry 8 mL reaction vial (provided with a magnetic stirrer, iron anode and nickel cathode), 0.2 mmol of 4-iodobenzoic acid methyl ester, 0.3 mmol of vinyl boronic acid pinacol ester, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine are added, 3.0 mL of super dry DMA is added as a solvent, and the system is protected by inert gas and sealed;

[0064] II. The sealed system of step I is stirred at room temperature, a constant current of 1 mA is continuously supplied, and the reaction is carried out for 10 h to obtain a crude product;

[0065] III. The crude product obtained in step II is extracted, dried, and the solvent is removed by distillation under reduced pressure, and then thin layer chromatography is used for separation and purification to obtain a product, which is identified as 1,1-bis aryl compound (3-2) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and the structural formula thereof is:

[0066]

[0067] The purity is 99%, and the yield is 71%; and the nuclear magnetic data analysis is as follows: 1 H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 8.3 Hz, 4H), 7.31 (d, J = 8.3 Hz, 4H), 4.39 (t, J = 8.3 Hz, 1H), 3.88 (s, 6H), 1.61 (d, J = 8.3 Hz, 2H), 1.06 (s, 12H).

[0068] 13 C NMR (101 MHz, CDCl3) δ 167.07, 151.10, 129.84, 128.22, 127.78, 83.45, 52.08, 46.58, 24.65.

[0069] Embodiment 3:

[0070] The method for synthesizing 1,1-bis aryl compounds by using non-activated olefins in the embodiment is specifically carried out in the following manner:

[0071] I. In a dry 8 mL reaction vial (equipped with a magnetic stir bar, iron anode and nickel cathode), 0.2 mmol of 3-iodobenzo[b]thiophene, 0.3 mmol of vinylboronic acid pinacol ester, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine were added, 3.0 mL of super dry DMA was added as solvent, and the system was protected by inert gas and sealed;

[0072] II. The sealed system of step I was stirred at room temperature, a constant current of 1 mA was continuously supplied, and the reaction was carried out for 10 h to obtain a crude product;

[0073] III. The crude product obtained in step II was extracted, dried, and the solvent was removed by distillation under reduced pressure, and then the product was separated and purified by thin layer chromatography. The product was identified as 1,1-diaryl compound (3-3) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0074]

[0075] The purity was 99% and the yield was 41%; the nuclear magnetic data analysis was as follows: 1 H NMR (400 MHz, CDCl3) δ 7.85-7.79 (m, 2H), 7.79-7.74 (m, 2H), 7.32-7.27 (m, 4H), 7.15 (s, 2H), 5.00 (t, J = 8.1 Hz, 1H), 1.77 (d, J = 8.1 Hz, 2H), 1.05 (s, 12H).

[0076] 13 C NMR (101 MHz, CDCl3) δ 140.80, 140.39, 138.38, 124.21, 123.87, 122.84, 122.40, 122.12, 83.37, 34.71, 24.63.

[0077] Example 4:

[0078] The method of the present embodiment for synthesizing 1,1-diaryl compounds using non-activated olefins is specifically carried out as follows:

[0079] I. In a dry 8 mL reaction vial (equipped with a magnetic stir bar, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 0.3 mmol of vinyltrimethylsilane, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine, 0.1 mmol of 2,6-dimethylpyridine were added, 3.0 mL of super dry DMA was added as solvent, and the system was sealed and protected by inert gas;

[0080] II. The sealed system of step I was stirred at room temperature, a constant current of 1 mA was continuously supplied, and the reaction was carried out for 10 h to obtain a crude product;

[0081] III. The crude product obtained in step II was extracted, dried, and distilled under reduced pressure to remove the solvent, and then separated and purified by thin layer chromatography to obtain a product, which was identified as a 1,1-diaryl compound (3-4) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0082]

[0083] The purity is 99%, and the yield is 85%; and the nuclear magnetic data analysis is: 1 H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.4 Hz, 4H), 7.55 (d, J = 8.0 Hz, 4H), 7.44 (t, J = 8.1 Hz, 8H), 7.34 (t, J = 7.3 Hz, 2H), 4.20 (t, J = 8.0 Hz, 1H), 1.51 (d, J = 8.0 Hz, 2H), -0.09 (s, 9H).

[0084] 13 C NMR (101 MHz, CDCl3) δ 146.28, 141.09, 139.05, 128.80, 128.06, 127.25, 127.14, 127.09, 46.86, 24.36, -0.98.

[0085] Example 5:

[0086] This embodiment is a method for synthesizing a 1,1-diaryl compound by using a non-activated olefin, which is specifically carried out as follows:

[0087] I. In a dry 8 mL reaction vial (equipped with a magnetic stir bar, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 0.3 mmol of dimethylphenylvinylsilane, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine were added, 3.0 mL of super dry DMA was added as solvent, and the system was protected by inert gas and sealed;

[0088] II. The sealed system of step I was stirred at room temperature, a constant current of 1 mA was continuously supplied, and the reaction was carried out for 10 h to obtain a crude product;

[0089] III. The crude product obtained in step II was extracted, dried, and the solvent was removed by distillation under reduced pressure, and then the product was separated and purified by thin layer chromatography, and identified as 1,1-diaryl compound (3-5) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0090]

[0091] The purity was 99% and the yield was 83%; and the nuclear magnetic data analysis was as follows: 1 H NMR (400 MHz, CDCl3) δ 7.56-7.51 (m, 4H), 7.48-7.44 (m, 4H), 7.43-7.36 (m, 6H), 7.35-7.26 (m, 9H), 4.11 (t, J = 8.0 Hz, 1H), 1.70 (d, J = 8.0 Hz, 2H), 0.09 (s, 6H).

[0092] 13 C NMR (101 MHz, CDCl3) δ 145.97, 141.11, 139.16, 139.12, 133.73, 128.95, 128.83, 128.11, 127.86, 127.26, 127.18, 127.12, 46.71, 23.66, -2.48.

[0093] Example 6:

[0094] The method of the present embodiment for synthesizing 1,1-diaryl compounds by using non-activated olefins is specifically carried out as follows:

[0095] I. In a dry 8 mL reaction vial (equipped with a magnetic stir bar, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 0.4 mmol of vinylcyclohexane, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine were added, and 3.0 mL of super dry DMA was added as solvent.

[0096] The system was protected by inert gas and sealed;

[0097] II. The sealed system of step I was stirred at room temperature, a constant current of 1 mA was continuously supplied, and the reaction was carried out for 10 h to obtain a crude product;

[0098] III. The crude product obtained in step II was extracted, dried, and the solvent was removed by distillation under reduced pressure. Then, thin layer chromatography was used for separation and purification to obtain a product, which was identified as 1,1-diaryl compound (3-6) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is as follows:

[0099]

[0100] The purity was 99%, and the yield was 48%. The nuclear magnetic data analysis was as follows: 1H NMR (400 MHz, CDCl3) δ 7.61-7.56 (m, 4H), 7.56-7.50 (m, 4H), 7.42 (t, J = 7.7 Hz, 4H), 7.33 (dd, J = 16.1, 7.8 Hz, 6H), 4.16 (t, J = 7.9 Hz, 1H), 2.00 (t, J = 7.3 Hz, 2H), 1.83 (d, J = 12.6 Hz, 2H), 1.75-1.58 (m, 4H), 1.30-1.14 (m, 4H), 1.00 (qd, J = 11.5, 3.3 Hz, 2H).

[0101] 13 C NMR (101 MHz, CDCl3) δ 201.48, 136.61, 132.71, 128.55, 128.53, 77.31, 49.56, 41.07, 36.34, 36.25, 33.72, 29.81, 29.09.

[0102] Example 7:

[0103] This embodiment is a method for synthesizing 1,1-diaryl compound by using non-activated olefin, which is specifically carried out as follows:

[0104] I. In a dry 8 mL reaction vial (equipped with a magnetic stir bar, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 0.4 mmol of n-decene, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine were added, 3.0 mL of super dry DMA was added as solvent, and the system was protected by inert gas and sealed;

[0105] II. The sealed system of step I was stirred at room temperature, a constant current of 1 mA was continuously supplied, and the reaction was carried out for 10 h to obtain a crude product;

[0106] III. The crude product obtained in step II was subjected to extraction, drying, and removal of solvent by reduced pressure distillation, and then was separated and purified by thin layer chromatography to obtain a product, which was identified as a 1,1-diaryl compound (3-7) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0107]

[0108] The purity was 99%, and the yield was 55%; and the nuclear magnetic data analysis was as follows: 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 7.7 Hz, 4H), 7.55 (d, J = 7.8 Hz, 4H), 7.44 (t, J = 7.5 Hz, 4H), 7.35 (dd, J = 17.0, 7.8 Hz, 6H), 4.00 (t, J = 7.8 Hz, 1H), 2.13 (q, J = 7.3 Hz, 2H), 1.32 (d, J = 36.9 Hz, 14H), 0.90 (t, J = 6.6 Hz, 3H).

[0109] 13 C NMR (101 MHz, CDCl3) δ 144.51, 141.08, 139.05, 128.78, 128.35, 127.26, 127.12, 127.08, 50.86, 35.86, 31.98, 29.76, 29.69, 29.60, 29.40, 28.16, 22.77, 14.20.

[0110] Example 8:

[0111] The method of the present embodiment for synthesizing a 1,1-diaryl compound by using a non-activated olefin is specifically carried out as follows:

[0112] I. In a dry 8 mL reaction vial (equipped with a magnetic stir bar, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 0.4 mmol of ketobutrophenone (ketoprofen derivative), 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2·DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine were added, 3.0 mL of super dry DMA was added as solvent, and the system was sealed and protected by inert gas;

[0113] II. The sealed system of step I was stirred at room temperature, a constant current of 1 mA was continuously supplied, and the reaction was carried out for 10 h to obtain a crude product;

[0114] III. The crude product obtained in step II was extracted, dried, and the solvent was removed by vacuum distillation, and then the product was separated and purified by thin layer chromatography, and identified as 1,1-diaryl compound (3-8) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0115]

[0116] The purity is 99%, and the yield is 45%; and the nuclear magnetic data analysis is: 1 H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 7.5 Hz, 4H), 7.55 (d, J = 8.2 Hz, 4H), 7.45 (t, J = 7.7 Hz, 4H), 7.35 (t, J = 7.4 Hz, 2H), 7.30 (d, J = 8.3 Hz, 4H), 7.25 (d, J = 5.3 Hz, 2H), 7.12 (d, J = 8.1 Hz, 2H), 4.16 (tt, J = 11.3, 5.6 Hz, 2H), 3.96 (t, J = 7.9 Hz, 1H), 3.73 (q, J = 7.1 Hz, 1H), 2.46 (d, J = 7.2 Hz, 2H), 2.09 (q, J = 8.2, 7.7 Hz, 2H), 1.86 (tq, J = 13.5, 6.6 Hz, 1H), 1.65 (dt, J = 14.4, 6.5 Hz, 2H), 1.53 (dd, J = 7.1, 1.8 Hz, 3H), 0.90 (dd, J = 6.6, 1.8 Hz, 6H).

[0117] 13C NMR (101 MHz, CDC13) δ 174.90, 143.81, 143.75, 140.99, 140.62, 139.28, 137.97, 129.43, 128.84, 128.29, 128.27, 127.36, 127.30, 127.22, 127.10, 64.51, 50.29, 45.32, 45.16, 31.89, 30.26, 27.28, 22.50, 18.57.

[0118] Example 9:

[0119] The method of the present embodiment for synthesizing 1,1-diaryl compounds by using non-activated alkenes is carried out as follows:

[0120] I. In a dry 8 mL reaction vial (equipped with a magnetic stirrer, iron anode and nickel cathode), 0.2 mmol of iodobenzene, 1 bar of ethylene, 0.3 mmol of nBu4NBr, 0.015 mmol of NiBr2-DME, 0.018 mmol of 6,6-dimethyl-2,2-bipyridine and 0.1 mmol of 2,6-dimethylpyridine are added, 3.0 mL of super dry DMA is added as solvent, and the system is protected by inert gas and sealed;

[0121] II. The sealed system of step I is stirred at room temperature, a constant current of 1 mA is continuously supplied, and the reaction is carried out for 10 h to obtain a crude product;

[0122] III. The crude product obtained in step II is extracted, dried, and the solvent is removed by vacuum distillation, and then thin layer chromatography is used for separation and purification to obtain the product, which is identified as 1,1-diaryl compound (3-9) by nuclear magnetic hydrogen spectrum, carbon spectrum and mass spectrum, and its structural formula is:

[0123]

[0124] Purity 99%, yield 30%; its nuclear magnetic data analysis is: 1 H NMR (400 MHz, CDC13) δ 7.66 (d, J = 7.2 Hz, 4H), 7.62 (d, J = 8.0 Hz, 4H), 7.50 (t, J = 7.6 Hz, 4H), 7.44-7.38 (m, 6H), 4.32 (q, J = 7.2 Hz, 1H), 1.80 (d, J = 7.2 Hz, 3H).

[0125] 13C NMR (101 MHz, CDC13) δ 145.50, 141.09, 139.15, 128.84, 128.15, 127.29, 127.19, 127.14, 44.30, 22.00.

[0126] The above-described embodiments are only preferred embodiments of the present application, and are not intended to limit the present application in any form. Other variations and modifications can be made without departing from the technical scope of the present application as recited in the claims.

Claims

1. A method for synthesizing 1,1-bisaryl compounds using non-activated olefins, characterized in that The method is specifically carried out as follows:

1. Place an anode electrode and a cathode electrode in a reaction bottle, add a non-activated olefin compound, halogenated aromatic hydrocarbon, electrolyte, nickel catalyst, ligand and base under N2 atmosphere, then add ultra-dry solvent and seal the system; The halogenated aromatic hydrocarbon is iodobenzene, methyl 4-iodobenzoate, p-fluoroiodobenzene, p-chloroiodobenzene, 4'-iodoacetophenone, 4-iodoanisole, 4-iodobenzonitrile or 3-iodobenzo[b]thiophene; The electrolyte is tetrabutylammonium bromide; The base in step 1 is 2,6-lutidine; The non-activated olefin compound is vinylboronic acid pinacol ester, trimethylvinylsilane, dimethylphenylvinylsilane, vinylcyclohexane, n-pentene, n-hexene, n-heptene, 4-phenyl-1-butene or keto-ibuprofen butene ester; The ligand is 6,6-dimethyl-2,2-bipyridine; The nickel catalyst is ethylene glycol dimethyl ether nickel bromide; 2. Pass a constant current through the closed system of step 1 and stir to obtain a crude product; 3. The crude product obtained in step 2 is subjected to reduced pressure distillation to remove the solvent, and then separated and purified by thin layer chromatography to obtain the 1,1-bisaryl compound; Step 2: Control the constant current to 1 mA; Step 2 reaction formula: , wherein chemical formula (1) is a halogenated aromatic hydrocarbon and chemical formula (2) is a non-activated olefin compound.

2. A method for synthesizing 1,1-bisaryl compounds using non-activated olefins according to claim 1, characterized in that The ultra-dry solvent in step 1 is ultra-dry N , N -dimethylacetamide.

3. A method for synthesizing 1,1-bisaryl compounds using non-activated olefins according to claim 1, characterized in that The amount ratio of the halogenated aromatic hydrocarbon to the ultra-dry solvent in step 1 is 0.2 mmol: 3 mL; the amount ratio of the non-activated olefin compound to the ultra-dry solvent is 0.3~0.4 mmol: 3 mL; the amount ratio of the nickel catalyst to the ultra-dry solvent is 0.015 mmol: 3 mL; the amount ratio of the ligand to the ultra-dry solvent is 0.018 mmol: 3 mL; the amount ratio of the electrolyte to the ultra-dry solvent is 0.3 mmol: 3 mL; and the amount ratio of the base to the ultra-dry solvent is 0.1 mmol: 3 mL.

4. The method for synthesizing 1,1-bisaryl compounds using non-activated olefins according to claim 1, characterized in that In step 1, the anode electrode is an iron electrode, and the cathode electrode is a nickel electrode.

5. The method for synthesizing 1,1-bisaryl compounds using non-activated olefins according to claim 1, characterized in that In step 2, the reaction temperature was controlled at 30-50°C and the continuous power-on time was 10 hours.

6. The method for synthesizing 1,1-bisaryl compounds using non-activated olefins according to claim 1, characterized in that In step 2, the reaction progress was monitored by TLC.

7. The method for synthesizing 1,1-bisaryl compounds using non-activated olefins according to claim 1, characterized in that The solvent used for the thin layer chromatography separation and purification in step 3 is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of (5-50):1.

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