A method for the nickel / photocatalytic synthesis of 1,1-diaryl-2-alkyl compounds

Abstract

The application belongs to the field of organic synthesis, and particularly relates to a method for synergistically synthesizing 1,1-diaryl-2-alkyl compounds by using nickel and light. The method comprises the following steps: using styrene derivatives, p-bromoacetophenone and tert-butyl bromide as raw materials, and mixing a metal nickel catalyst (nickel bis(acetylacetone)), a photocatalyst (1,2,3,5-tetrakis(carbazole-9-yl)-4,6-dicyano benzene), a nitrogen ligand ((4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bis-4H-imidazole), a Bronsted base (N,N-dicyclohexylmethylamine), a reducing agent (1,4-dihydropyridine derivatives) and an organic solvent (glycol dimethyl ether, isopropyl ether) to generate a three-component cross-coupling reaction and synthesize 1,1-diaryl-2-alkyl compounds with one chiral center. The three-component cross-coupling reaction is realized by using nickel and light, so that the use of a metal reducing agent is avoided, and the preparation raw materials are not needed. The method has the advantages of high reaction yield, high enantiomeric selectivity, fast reaction speed, easy-to-obtain raw materials and simple process.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a method for synthesizing 1,1-diaryl-2-alkyl compounds by light / nickel synergistic catalysis. BACKGROUND

[0002] Carbon-carbon bond (C-C bond) is an important component of organic compounds, and how to efficiently construct various complex carbon-carbon bonds has always been a research focus in the development of organic chemistry. Transition metal-catalyzed cross-coupling reaction, as one of the most efficient methods for constructing carbon-carbon bond / carbon-heteroatom bond, includes Heck reaction, Negishi coupling and Suzuki coupling. It has been widely used in organic synthesis, drug synthesis and material synthesis, and was awarded the Nobel Prize in Chemistry in 2010.

[0003] Compared with palladium and cobalt, nickel is a cheap metal with high content in the earth's crust, and has advantages in cross-coupling reaction due to its inherent characteristics. Due to the relatively small atomic radius of nickel, C(sp 3 )-Ni is more difficult to undergo β-H elimination reaction. In addition, nickel has more valence states, and the known oxidation states of nickel compounds include Ni(0), Ni(I), Ni(II), Ni(III), and Ni(IV). However, both traditional cross-coupling and reductive cross-coupling reactions have certain limitations. For example, the nucleophilic reagents in traditional cross-coupling reaction are generally organometallic reagents such as RMgX and RZnX. These nucleophilic reagents mostly need to be prepared in advance and are sensitive to air and water. Although reductive cross-coupling reaction avoids the use of water and oxygen sensitive metal organic reagents, it still needs to use some solid reducing agents such as zinc powder, manganese powder and magnesium powder. These metal reducing agents are not easy to recover, thus causing certain material waste. Therefore, researchers have been seeking materials to avoid or replace these metal reducing agents.

[0004] In recent years, visible light / transition metal synergistic catalytic system has been widely used in the development of new and efficient organic synthesis methods. In particular, visible light / nickel synergistic catalysis has attracted much attention from chemists due to its multiple oxidation states. This synergistic catalysis strategy not only expands the substrate range of the coupling reaction, but also avoids the use of equivalent metal reagents, is simple to operate, and has wide substrate applicability. The present application provides a kind of nickel light synergistic catalysis intermolecular three-component cross-coupling reaction to obtain a kind of diaryl compound containing chiral center. One-step olefin double carbon functionalization is realized to construct complex organic compounds, and the substrate is cheap and easy to obtain, the process is simple, and the reaction conditions are mild. SUMMARY

[0005] The application provides a nickel-catalyzed different-substituent styrene derivative, and a 1,1-diaryl-2-alkyl compound can be obtained through a three-component reductive cross-coupling reaction of p-bromoacetophenone and tert-butyl bromide, and the synthesis method is simple and efficient.

[0006]

[0007] The different-substituent styrene shown in formula 1, the p-bromoacetophenone shown in formula 2 and the tert-butyl bromide shown in formula 3 are mixed with an organic solvent to perform a reductive cross-coupling reaction in the presence of a transition metal bisacetylacetone nickel catalyst, (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bis-4H-imidazole as a ligand, N,N-dicyclohexylmethylamine as a base and 1,2,3,5-tetrakis(carbazole-9-yl)-4,6-dicyano benzene as a photocatalyst to synthesize the 1,1-diaryl-2-alkyl compound with a chiral center shown in formula 4.

[0008] The method can realize the three-component cross-coupling reaction of the nickel / photocatalyzed styrene derivative, the p-bromoacetophenone and the tert-butyl bromide to generate the 1,1-diaryl-2-alkyl compound, and the yield is excellent.

[0009] Preferably, the reaction is carried out under the protection of inert gas argon.

[0010] Preferably, the organic solvent is ethylene glycol dimethyl ether and isopropyl ether.

[0011] Preferably, the molar ratio of the styrene derivative shown in formula 1, the p-bromoacetophenone shown in formula 2, the tert-butyl bromide shown in formula 3, the nickel catalyst and the photocatalyst in the reaction is 1-2:1-2:1-2:0.05-0.2:0.004-0.02, and the reaction temperature is 25 DEG C.

[0012] Preferably, the method can be used to synthesize the 1,1-diaryl-2-alkyl compound with the following structure.

[0013]

[0014]

[0015] Under the action of a transition metal catalyst bisacetylacetone nickel and a nitrogen ligand (4S, 4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bis-4H-imidazole, a three-component cross-coupling reaction of styrene, p-bromoacetophenone and tert-butyl bromide is carried out, and finally a 1,1-diaryl-2-alkyl compound is prepared.

[0016] The technical scheme of the present application can achieve at least one of the following beneficial effects:

[0017] The raw materials used in the synthesis method of the present application are cheap and easy to obtain;

[0018] The synthesis method of the present application adopts a one-pot method, which has fewer reaction steps, reduces the loss of raw materials, and improves the yield of the product;

[0019] The operation steps required by the present application are relatively simple, do not require extreme temperature rise or temperature drop, and only require normal temperature and pressure to react, which is safe and convenient;

[0020] In the present application, R can be selected in many ways, so the method of the present application is more widely applicable and can synthesize a variety of 1,1-diaryl-2-alkyl compounds with chiral centers. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1A The hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0022] Figure 1B The carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0023] Figure 2A The hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0024] Figure 2B The carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0025] Figure 3A The hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0026] Figure 3B The carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0027] Figure 4A The hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0028] Figure 4B The carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0029] Figure 5A The hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1 is shown in the figure;

[0030] Figure 5B Carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0031] Figure 6A Hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0032] Figure 6B Carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0033] Figure 7A Hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0034] Figure 7B Carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0035] Figure 8A Hydrogen spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1;

[0036] Figure 8B Carbon spectrum nuclear magnetic resonance spectrum of the product obtained in Example 1. DETAILED DESCRIPTION

[0037] In order to facilitate the understanding of those skilled in the art, the concept of the present application is further illustrated below in conjunction with examples. The specific

[0038] The description is not a limitation of the present application, but is only for the convenience of those skilled in the art to understand the technical solution. The various raw materials involved in the description are purchased from the market or synthesized simply, and other drugs are purchased from Anjie, Bide, Sigma-Aldrich, Acros, Alfa Aesar, Adamas-beta or J&K. The nuclear magnetic resonance spectrometer is Bruker 400M.

[0039] Experimental Example 1

[0040] In a pre-dried Schlenk flask with a magnetic bar, nickel bis(acetylacetonate) (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol) and 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyano-benzene (6.4 mg, 8 mol%) were added in sequence. The flask was transferred into an argon-filled glove box, 1.0 mL of ethyleneglycol dimethyl ether and 1.0 mL of isopropyl ether were added into the flask, and the mixture was stirred at room temperature for 30 min. 1.0 mL of p-tert-butylstyrene (16.1 mg, 0.1 mmol), p-bromoacetophenone (39.8 mg, 0.2 mmol), tert-butyl bromide (41.1 mg, 0.3 mmol) in dimethyl ether (DME) were added into the flask. After the flask was sealed, it was taken out of the glove box, and the reaction was carried out under blue LED irradiation at room temperature for 24 h. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to give the target product 1-(3,3-dimethyl-1-p-tert-butylphenylbutyl)-4-acetylbenzene (27.6 mg, 82% yield). The proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of the product were Figure 1A and Figure 1B , and the spectral data were: 1 H NMR (400 MHz, CDC13) δ 7.88-7.80 (m, 2H), 7.40 (d, J = 8.3 Hz, 2H), 7.29-7.24 (m, 3H), 7.18 (d, J = 8.4 Hz, 2H), 4.08 (dd, J = 7.6, 5.7 Hz, 1H), 2.55 (s, 3H), 2.21-2.01 (m, 2H), 1.26 (s, 9H), 0.83 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 135.0, 128.6, 128.1, 127.2, 125.4, 49.2, 48.0, 31.5, 31.3, 30.2, 26.5 ppm.

[0041] The starting materials in Example 1 were changed, and seven groups of experiments were designed as follows, wherein the first group of experiments is Example 1, and the nuclear magnetic resonance spectrum of the product is shown in Figure 1. The nuclear magnetic resonance spectra of the products of the remaining groups 2-8 correspond to the serial numbers of the corresponding examples. The structural formula of the product in each of Examples 1-8 is listed in the table. In the eight examples, only the type of styrene derivative used is different, and the other raw materials, amounts, conditions, etc. remain the same. The last column lists the yield and enantiomeric excess percentage (e.e. value) of the product of each example.

[0042]

[0043]

[0044] Experimental Example 2

[0045] In a pre-dried photo reaction bottle with a magnet, nickel bisacetylacetone (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bis-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol) and 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyano benzene (6.4 mg, 8 mol%) were sequentially added, and the reaction bottle was transferred to an argon glove box, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added, and stirred at room temperature for 30 minutes. 1.0 mL of p-trifluoromethylstyrene (17.2 mg, 0.1 mmol), p-bromophenacyl bromide (39.8 mg, 0.2 mmol), and t-butyl bromide (41.1 mg, 0.3 mmol) in dimethyl ether (DME) were added. After sealing the bottle, it was taken out of the glove box, and under blue LED irradiation, it was reacted at room temperature for 24 hours. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product 1-(3,3-dimethyl-1-p-trifluoromethylphenylbutyl)-4-acetylbenzene (30.3 mg, 87% yield). The proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of the product are Figure 2A and Figure 2B , and the spectral data are: 1H NMR (400 MHz, CDC13) δ 7.88 (d, J = 8.4 Hz, 2H), 7.55 - 7.49 (m, 2H), 7.39 (dd, J = 8.2, 6.1 Hz, 4H), 4.18 (t, J = 6.6 Hz, 1H), 2.56 (s, 3H), 2.13 (dd, J = 7.3, 6.7 Hz, 2H), 0.84 (s, 9H) ppm. 13 C NMR (101 MHz, CDC13) δ 197.6, 151.2, 149.8, 135.3, 128.8, 128.0, 127.9, 125.6, 125.6, 48.9, 48.3, 31.6, 30.1, 26.5 ppm.

[0046] Experimental Example 3

[0047] In a pre-dried photo reaction flask with a magnet, nickel bisacetylacetonate (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol) and 1,2,3,5-tetrakis(carbazol-9-yl(carbazol-9-yl)-4,6-dicyano benzene (6.4 mg, 8 mol%) were sequentially added, the reaction flask was transferred into an argon-protected glove box, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added thereto, and stirring was performed at room temperature for 30 minutes. A solution of 1.0 mL of p-fluorostyrene (12.2 mg, 0.1 mmol), p-bromophenacyl bromide (39.8 mg, 0.2 mmol), t-butyl bromide (41.1 mg, 0.3 mmol) in dimethyl ether (DME) was added thereto. After the flask was sealed, it was taken out of the glove box, and reacted at room temperature for 24 hours under blue LED irradiation. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product 1-(3,3-dimethyl-1-p-fluorophenylbutyl)-4-acetylbenzene (23.6 mg, 79% yield). The proton nuclear magnetic resonance spectrum and the carbon nuclear magnetic resonance spectrum of the product were Figure 3A and Figure 3B , and the spectral data were: 1H NMR (400 MHz, CDC13) δ 7.86 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 7.28 - 7.20 (m, 2H), 6.95 (t, J = 8.7 Hz, 2H), 4.10 (t, J = 6.7 Hz, 1H), 2.55 (s, 3H), 2.08 (dd, J = 6.7, 2.1 Hz, 2H), 0.83 (s, 9H) ppm. 13 C NMR (101 MHz, CDC13) δ 197.7, 152.2, 141.4, 135.1, 129.1, 129.0, 128.7, 127.8, 115.5, 115.2, 49.2, 47.6, 31.5, 30.2, 26.5 ppm.

[0048] Experimental Example 4

[0049] In a pre-dried photo reaction flask with a magnet, nickel bisacetylacetonate (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol), and 1,2,3,5-tetrakis(carbazol-9-yl(carbazol-9-yl)-4,6-dicyano benzene (6.4 mg, 8 mol%) were sequentially added, the reaction flask was transferred to an argon-protected glove box, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added thereto, and stirring was performed at room temperature for 30 minutes. A solution of 1.0 mL of 3-fluorostyrene (12.2 mg, 0.1 mmol), p-bromoacetophenone (40 mg, 0.2 mmol), and t-butyl bromide ((54.8 mg, 0.4 mmol) in dimethyl ether (DME) was added thereto. After the flask was sealed, it was taken out of the glove box, and the reaction was performed at room temperature for 24 hours under blue LED irradiation. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product 1-(3,3-dimethyl-1-p-fluorophenylbutyl)-4-acetylbenzene (15.5 mg, 52% yield). The nuclear magnetic resonance hydrogen spectrum and the nuclear magnetic resonance carbon spectrum of the product were Figure 4A and Figure 4B , and the spectral data were: 1H NMR (400 MHz, CDC13) δ: 7.87 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.09-6.80 (m, 4H), 4.11 (t, J = 6.7 Hz, 1H), 2.56 (s, 3H), 2.09 (d, J = 6.7 Hz, 2H), 0.84 (s, 9H) ppm. 13 C NMR (101 MHz, CDC13) δ: 197.7, 151.6, 135.2, 130.0, 130.0, 128.8, 128.7, 127.9, 123.4, 114.6, 114.4, 113.2, 113.0, 77.3, 77.0, 76.7, 49.0, 48.1, 31.5, 30.1, 26.5 ppm.

[0050] Experimental Example 5

[0051] In a pre-dried photo reaction flask with a magnet, nickel bisacetylacetonate (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol) and 1,2,3,5-tetrakis(carbazol-9-yl(carbazol-9-yl)-4,6-dicyanobenzene (6.4 mg, 8 mol%) were sequentially added, the reaction flask was transferred into an argon-protected glove box, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added thereto, and stirring was performed at room temperature for 30 minutes. A solution of 1.0 mL of 2-fluorostyrene (12.2 mg, 0.1 mmol), p-bromoacetophenone (40 mg, 0.2 mmol), and tert-butyl bromide ((54.8 mg, 0.4 mmol) in dimethyl ether (DME) was added thereto. After the flask was sealed, it was taken out of the glove box, and the reaction was performed at room temperature for 24 hours under blue LED irradiation. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product 1-(3,3-dimethyl-1-p-fluorophenylbutyl)-4-acetylbenzene (14.0 mg, 47% yield). The proton nuclear magnetic resonance spectrum and the carbon nuclear magnetic resonance spectrum of the product were Figure 5A and Figure 5B , and the spectral data were: 1H NMR (400 MHz, CDC13) δ 7.88-7.85 (m, 2H), 7.45-7.40 (m, 2H), 7.33 (m, IH), 7.19-7.11 (m, IH), 7.08 (dd, J = 7.5, 1.4 Hz, IH), 6.98 (m, IH), 4.50 (t, J = 6.7 Hz, IH), 2.55 (s, 3H), 2.11 (d, J = 6.7 Hz, 2H), 0.85 (s, 9H) ppm. 13 CNMR (101 MHz, CDC13) δ 197.8, 151.2, 135.2, 128.6, 128.6, 128.1, 127.8, 127.7, 124.2, 115.7, 115.5, 77.3, 77.0, 76.7, 48.1, 40.1, 31.5, 30.03, 26.5 ppm.

[0052] Experimental Example 6

[0053] In a pre-dried photo reaction flask with a magnet, nickel bisacetylacetonate (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol), and 1,2,3,5-tetrakis(carbazol-9-yl(carbazol-9-yl)-4,6-dicyano benzene (6.4 mg, 8 mol%) were sequentially added, the reaction flask was transferred into a glove box under argon, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added, and stirring was performed at room temperature for 30 minutes. A solution of 1.0 mL of 3-chlorostyrene (13.8 mg, 0.1 mmol), p-bromoacetophenone (40 mg, 0.2 mmol), and tert-butyl bromide ((54.8 mg, 0.4 mmol) in dimethyl ether (DME) was added. After the flask was sealed, it was taken out of the glove box, and the reaction was performed at room temperature for 24 hours under blue LED irradiation. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product 1-(3,3-dimethyl-1-p-fluorophenylbutyl)-4-acetylbenzene (15.7 mg, 50% yield). The proton nuclear magnetic resonance spectrum and the carbon nuclear magnetic resonance spectrum of the product were Figure 6A and Figure 6B, spectral data:1H NMR (400 MHz, CDCI3) δ 7.88-7.84 (m, 2H), 7.35 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 4.0 Hz, 3H), 4.09 (t, J = 6.7 Hz, 1H), 2.55 (s, 3H), 2.08 (dd, J = 6.7, 1.4 Hz, 2H), 0.83 (s, 9H) ppm. 13 C NMR (101 MHz, CDCI3) δ 197.7, 151.8, 144.2, 135.2, 132.0, 129.0, 128.8, 128.7, 128.6, 127.8, 77.3, 77.0, 76.7, 49.1, 47.8, 31.5, 30.2, 26.5 ppm.

[0054] Experimental Example 7

[0055] In a pre-dried photo reaction flask with a magnet, nickel bisacetylacetonate (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol) and 1,2,3,5-tetrakis(carbazol-9-yl(carbazol-9-yl)-4,6-dicyano benzene (6.4 mg, 8 mol%) were added successively, the reaction flask was transferred into an argon-protected glove box, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added thereto, and stirred at room temperature for 30 minutes. A solution of 1.0 mL of 2-chlorostyrene (13.8 mg, 0.1 mmol), p-bromoacetophenone (40 mg, 0.2 mmol), t-butyl bromide ((54.8 mg, 0.4 mmol) in dimethyl ether (DME) was added thereto. After the flask was sealed, it was taken out of the glove box, and reacted at room temperature for 24 hours under blue LED irradiation. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product 1-(3,3-dimethyl-1-p-fluorophenylbutyl)-4-acetylbenzene (19.2 mg, 61% yield). The proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of the product were Figure 7A and Figure 7Bppm.1H NMR (400 MHz, CDC13) δ 7.87 (d, J = 8.6 Hz, 3H), 7.39 - 7.35 (m, 2H), 7.29 (d, J = 8.0 Hz, 1H), 7.20 - 7.17 (m, 2H), 4.09 (t, J = 6.7 Hz, 1H), 2.56 (s, 3H), 2.09 (dd, J = 6.7, 5.4 Hz, 2H), 0.84 (s, 9H) ppm. 13 C NMR (101 MHz, CDC13) δ 197.8, 151.5, 147.9, 135.4, 134.4, 130.0, 128.9, 128.0, 126.5, 126.0, 49.0, 48.2, 44.6, 31.7, 30.3, 26.7, 21.5 ppm.

[0056] Experimental Example 8

[0057] In a pre-dried photo reaction flask with a magnet, nickel bisacetylacetonate (2.6 mg, 10 mol%), (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bi-4H-imidazole (5.6 mg, 0.011 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 0.3 mmol), 1,4-dihydropyridine derivative (76.0 mg, 0.2 mmol), and 1,2,3,5-tetrakis(carbazol-9-yl(carbazol-9-yl)-4,6-dicyanobenzene (6.4 mg, 8 mol%) were sequentially added, and the reaction flask was transferred to an argon-protected glove box, 1.0 mL of ethylene glycol dimethyl ether and 1.0 mL of isopropyl ether were added thereto, and stirred at room temperature for 30 minutes. A solution of 1.0 mL of p-methylstyrene (11.8 mg, 0.1 mmol), p-bromoacetophenone (39.8 mg, 0.2 mmol), and t-butyl bromide (41.1 mg, 0.3 mmol) in dimethyl ether (DME) was added thereto. After sealing the flask, it was taken out of the glove box, and reacted at room temperature for 24 hours under blue LED irradiation. The crude product was separated by silica gel column chromatography using petroleum ether (PE) and ethyl acetate (EA) (petroleum ether: ethyl acetate = 15:1) to obtain the target product chiral 1-(3,3-dimethyl-1-p-methylphenylbutyl)-4-acetophenone (25.0 mg, 85% yield). The proton nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum of the product were Figure 8A and Figure 8B Spectrum data: 1H NMR (400 MHz, CDC13) δ 7.85 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 4.08 (t, J = 6.7 Hz, 1H), 2.54 (s, 3H), 2.28 (s, 3H), 2.09 (d, J = 6.6 Hz, 2H), 0.83 (s, 9H). 13 C NMR (101 MHz, CDC13) δ 197.8, 152.7, 142.8, 135.7, 134.9, 129.3, 128.7, 127.9, 127.5, 49.1, 48.0, 31.5, 30.2, 26.5, 20.9 ppm. 3 C NMR (101 MHz, CDC13) δ 197.8, 152.7, 142.8, 135.7, 134.9, 129.3, 128.7, 127.9, 127.5, 49.1, 48.0, 31.5, 30.2, 26.5, 20.9 ppm.

Claims

1. A method for the synthesis of 1,1-diaryl-2-alkyl compounds by nickel / photocatalysis, characterized in that: The 1,1-diaryl-2-alkyl compound shown in Formula 4 was synthesized by a three-component cross-coupling reaction using substituted styrene as shown in Formula 1, p-bromoacetophenone as shown in Formula 2, and tert-butyl bromide as shown in Formula 3, in the presence of a nickel catalyst, a nitrogen ligand, a base, and a photocatalyst, mixed with an organic solvent. Where R is selected from trifluoromethyl, fluorine atom, chlorine atom, methyl, tert-butyl; The nickel catalyst is nickel diacetylacetone; the nitrogen ligand is (4S,4'S)-1,1'-bis(3-tert-butylphenyl)-4,4',5,5'-tetrahydro-4,4'-bis[(1S)-1-methylpropyl]-2,2'-bis-4H-imidazolium; the base is N,N-dicyclohexylmethylamine; and the photocatalyst is 1,2,3,5-tetra(carbazole-9-yl)-4,6-dicyanophenyl.

2. The synthesis method according to claim 1, characterized in that, The reaction was carried out under the protection of the inert gas argon.

3. The synthesis method according to claim 1, characterized in that, The organic solvents mentioned are ethylene glycol dimethyl ether and isopropyl ether.

4. The synthesis method according to claim 1, characterized in that, In the reaction, the molar ratio of the styrene derivative shown in Formula 1, p-bromoacetophenone shown in Formula 2, tert-butyl bromide shown in Formula 3, nickel catalyst, and photocatalyst is 1–2:1–2:1–2:0.05–0.2:0.004–0.02; the reaction temperature is 25°C.

5. The synthesis method according to claim 1, characterized in that, The styrene derivatives and the chiral 1,1-diaryl-2-alkyl compounds mentioned are listed in one of the following tables: 。

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