A method for synthesizing an (r)-1,3-diarylbutenyl compound

Abstract

The application discloses a synthesis method of (R)-1,3-diarylbutene compounds and belongs to the field of organic synthesis. Under visible light, a compound shown in formula 1 and a compound shown in formula 2 are used as raw materials, and under the conditions of a chiral ligand shown in formula 3, a nickel catalyst, a photocatalyst, a reducing agent and a base, a (R)-1,3-diarylbutene compound shown in formula 4 is obtained. The raw material synthesis method is simple, cheap, simple in operation steps and mild in reaction conditions.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of organic synthesis, and particularly relates to a synthesis method of (R)-1,3-diarylbutene compound. BACKGROUND

[0002] Nickel-catalyzed reductive cross-coupling reactions between two electrophiles have become a powerful tool for the construction of carbon-carbon bonds. Compared with traditional cross-coupling reactions such as Suzuki-Miyaura, Kumada, Negishi and Hiyama, the reductive coupling strategy avoids the use of water and oxygen-sensitive organometallic reagents as cross-coupling agents, thereby improving the functional group tolerance. The reaction using superstoichiometric heterogeneous metal reductants may have some disadvantages, such as stirring effect, metal activity and generation of stoichiometric metal waste. Most commonly, soluble organic reductants (TDAE) are used as reductants for the coupling reaction of halogenated aromatic compounds. The present application uses a nickel / visible light-involved redox synergistic catalysis strategy to realize the asymmetric reductive cross-coupling reaction of arylalkyl bromide and benzyl chloride, and successfully prepares enantiomerically enriched olefin compounds, which provides high-value modules for further chemical conversion. In addition, the asymmetric reduction reaction has mild conditions, avoids the use of reductive metal, and also avoids the use of water and air-sensitive organometallic reagents. The advantages of this reaction also include good substrate functional group compatibility, and the light catalyst converts light energy into chemical energy.

[0003] The target product analog compounds in the present application have been reported, and specific examples are as follows:

[0004] 1. According to the reports of Hayashi, T.; Konishi, M.; Ito, H.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 4962-4963 and Hayashi, T.; Konishi, M.; Okamoto, Y.; Kabeta, K.; Kumada, M. J. Org. Chem. 1986, 51, 3772-3781, aryl Grignard reagent and vinyl bromide are selected, and the reaction is carried out at -10℃-0℃ in the presence of palladium catalyst and chiral phosphorus ligand to obtain diaryl olefin product.

[0005] 2. According to the report of A. H. Chemey, S. E. Reisman. J. Am. Chem. Soc., 2014, 136, 14365-14368, under the conditions of nickel catalysis and manganese powder as a reducing agent, zero degrees, asymmetric cross-coupling reaction of vinyl bromide and benzyl chloride is realized.

[0006] 3. Reductive cross-coupling reaction of vinyl bromide and NHP ester under the condition of nickel catalysis and TDAE reducing agent according to the report of document N. Suzuki, J. L. Hofstra, K. E. Poremba and S. E. Reisman. Org. Lett. 2017, 19, 2150-2153.

[0007] There have been some reports on the method for synthesizing diaryl olefin compounds, but these methods have more or less problems, such as the need to prepare a format reagent sensitive to air and water in advance, the use of an ultra-stoichiometric metal reducing agent, and the reaction conditions are not mild. Therefore, it is of great significance to develop a new asymmetric catalytic synthesis method which is more efficient, green and convenient. SUMMARY

[0008] The application adopts the strategy of redox cooperative catalysis of nickel / visible light to realize asymmetric reductive cross-coupling reaction and synthesize optically active olefin compounds under the irradiation of blue light, using alkenyl bromide and benzyl chloride as raw materials. The asymmetric reduction reaction condition is mild, avoiding the use of reducing metal.

[0009] The specific scheme is as follows:

[0010]

[0011] A synthesis method of (R)-1,3-diarylbutene compound, under the condition of 400-500nm visible light, using the compound shown as formula 1 and the compound shown as formula 2 as raw materials, under the condition of chiral ligand shown as formula 3, nickel catalyst, photocatalyst, reducing agent and base, to obtain (R)-1,3-diarylbutene compound shown as formula 4.

[0012] The photocatalyst is selected from one or more of transition metal ruthenium or iridium complex photocatalysts, non-metallic organic photocatalysts;

[0013] The reducing agent is selected from one or more of dihydropyridine reducing agents or tertiary amine reducing agents;

[0014] The base is selected from one or more of carbonate inorganic bases or tertiary amine organic bases;

[0015] R 1 selected from hydrogen, halogen group, ester group, methyl, methoxy or thiophene group;

[0016] R 2 selected from hydrogen, halogen group, trifluoromethyl, trifluoromethoxy, naphthyl;

[0017] Preferably, the nickel catalyst is selected from one or more of nickel chloride, nickel bromide, nickel iodide, bis-(1,5-cyclooctadiene) nickel, nickel bromide diethyleneglycol dimethyl ether complex, nickel bis(acetylacetonate).

[0018] Preferably, the photocatalyst is selected from one or more of tris(2-phenylpyridine) ruthenium, (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]ruthenium(III) hexafluorophosphate, 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyano-benzene;

[0019] Preferably, the reducing agent is selected from one or more of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester, 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid di-tert-butyl ester, N,N-dicyclohexylmethylamine, triethylamine;

[0020] Preferably, the base is selected from one or more of N,N-dicyclohexylmethylamine, triethylamine, cesium carbonate, sodium carbonate;

[0021] Preferably, the reaction is carried out in a solvent selected from one or more of dimethylsulfoxide, N,N-dimethylformamide, or dimethyloxymethane;

[0022] Preferably, R 1 selected from hydrogen, halogen, methoxy, ester, thienyl, R 2 selected from hydrogen, halogen, trifluoromethoxy;

[0023] Preferably, the molar ratio of the compound of formula 1 to the compound of formula 2, the nickel catalyst, the chiral ligand of formula 3, the photocatalyst, the reducing agent, and the base is (1-3):1:(0.1-1):(0.1-1):(0.01-1):(1-5):(1-5);

[0024] Preferably, the reaction is carried out under blue light of 425 nm wavelength;

[0025] Preferably, the reaction is carried out under inert gas protection, preferably, the inert gas is nitrogen or argon;

[0026] The technical solution of the present application can achieve at least one of the following beneficial effects:

[0027] The method of the present application has the advantages of cheap and readily available raw materials, easy generation, mild conditions, environmental protection and safety, etc.

[0028] The photocatalyst can be recycled, greatly reducing production costs;

[0029] The present application has simple experimental operation, and all the raw materials or catalysts used can be dissolved in the solvent, and the reaction is a homogeneous reaction.

[0030] By using the method of the present application, the (R)-1,3-diarylbutenyl compound with the following structure can be synthesized.

[0031]

[0032] BRIEF DESCRIPTION OF DRAWINGS

[0033] The drawings are the nuclear magnetic resonance spectra of the hydrogen spectrum and the carbon spectrum of the product of the examples, the serial number of the drawings corresponds to the serial number of the examples, wherein Figure 1A is the hydrogen spectrum of the target product of Example 1, Figure 1B is the carbon spectrum of the target product of Example 1; Figure 2A is the hydrogen spectrum of the target product of Example 2, Figure 2B is the carbon spectrum of the target product of Example 2; Figure 3A is the hydrogen spectrum of the target product of Example 3, Figure 3B is the carbon spectrum of the target product of Example 3; Figure 4A is the hydrogen spectrum of the target product of Example 4, Figure 4B is the carbon spectrum of the target product of Example 4; Figure 5A is the hydrogen spectrum of the target product of Example 5, Figure 5B is the carbon spectrum of the target product of Example 5; Figure 6A is the hydrogen spectrum of the target product of Example 6, Figure 6B is the carbon spectrum of the target product of Example 6; Figure 7A is the hydrogen spectrum of the target product of Example 7, Figure 7B is the carbon spectrum of the target product of Example 7; Figure 8A is the hydrogen spectrum of the target product of Example 8, Figure 8B is the carbon spectrum of the target product of Example 8; Figure 9A is the hydrogen spectrum of the target product of Example 9, Figure 9B is the carbon spectrum of the target product of Example 9. DETAILED DESCRIPTION

[0034] In order to facilitate the understanding of those skilled in the art, the concept of the present application will be further described below in conjunction with examples. The specific description of the following examples 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 specification are purchased from the market or simply synthesized, and other chemicals are purchased from Sigma-Aldrich, Acros, Alfa Aesar, TCI China, Adamas-beta or J&K. The nuclear magnetic resonance spectrometer is a 400MHz model of Bruker, deuterated CDCl3, and specific optical rotation is measured by an optical rotation instrument Autopol III of Rudolf Company, USA.

[0035] Example 1

[0036] In an argon-filled glove box, the chiral ligand shown in Formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethyl sulfoxide, followed by the addition of (E)-(2-bromovinyl)benzene (36.6 mg, 0.2 mmol), (1-chloroethyl)benzene (14.0 mg, 13 μL, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, and placed on a stirrer with blue light illumination at a wavelength of 425 nm at room temperature for 24 h. After the reaction was completed, 5 mL of ethyl acetate was added to the reaction solution, which was washed with saturated brine (3 x 10 mL), and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (17.9 mg, 86% yield, 90% ee). The specific optical rotation [α] D 25 = 13.2 (c = 0.6, CHCl3). The nuclear magnetic resonance spectral data are as follows: 1 H NMR (400 MHz, CDCl3) δ: 7.38-7.25 (m, 8H), 7.18 (dd, J = 18.6, 7.5 Hz, 3H), 6.40 (d, J = 5.1 Hz, 2H), 3.69-3.60 (m, 1H), 1.47 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ: 145.75, 137.66, 135.34, 128.63, 127.75, 127.45, 127.19, 126.36, 126.27, 77.92-76.42 (m), 42.69, 21.35.

[0037] Example 2

[0038] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-1-bromo-4-(2-bromovinyl)benzene (52.4 mg, 0.2 mmol), (1-chloroethyl)benzene (14.0 mg, 13 μL, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, and placed on a stirrer with blue light at a wavelength of 425 nm shining on it at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (24.6 mg, 86% yield, 91% ee). The specific optical rotation was [α] D 25 The nuclear magnetic resonance spectral data are as follows: 1 H NMR (400 MHz, CDC13) δ: 7.41-7.37 (m, 2H), 7.35-7.29 (m, 2H), 7.25 (d, J = 4.4 Hz, 3H), 7.19 (s, 1H), 6.41-6.29 (m, 2H), 3.62 (p, J = 6.9 Hz, 1H), 1.45 (d, J = 7.0 Hz, 3H). 13 CNMR (101 MHz, CDC13) δ: 145.38, 136.59, 136.19, 131.65, 128.66, 127.80, 127.47, 127.39, 126.45, 120.79, 77.46, 77.14, 76.82, 42.68, 21.20.

[0039] Example 3

[0040] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-1-fluoro-4-(2-bromovinyl)benzene (40 mg, 0.2 mmol), (1-chloroethyl)benzene (14.0 mg, 13 μL, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, and placed on a stirrer with blue light at a wavelength of 425 nm shining on it at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (20.3 mg, 90% yield, 91% ee). The specific optical rotation was [α] D 25 = -34.6 (c = 1.1, CHCl3). The nuclear magnetic resonance spectral data are as follows: 1 H NMR (400 MHz, CDCl3) δ: 7.30 (dd, J = 13.5, 7.0 Hz, 6H), 7.21 (d, J = 7.1 Hz, 2H), 7.04-6.93 (m, 3H), 6.41-6.24 (m, 2H), 3.63 (p, J = 6.8 Hz, 1H), 1.47 (d, J = 7.0 Hz, 3H). 13 CNMR (101 MHz, CDCl3) δ: 145.61, 135.08, 128.65, 127.94, 127.67 (d, J = 7.9 Hz), 127.40, 126.40, 115.56, 115.35, 77.15, 76.83, 42.64, 21.31.

[0041] Example 4

[0042] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-1-(2-bromovinyl)-4-methoxybenzene (52.4 mg, 0.2 mmol), (1-chloroethyl)benzene (14.0 mg, 13 μL, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, placed on a stirrer with blue light at a wavelength of 425 nm, and allowed to react at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (14.1 mg, 63% yield, 92% ee). The specific optical rotation [α] D 25 = -5.2 (c = 0., CHCl3). The nuclear magnetic resonance spectral data are as follows: 1 H NMR (400 MHz, CDCl3) δ: 7.28 (q, J = 6.8 Hz, 6H), 7.24-7.17 (m, 1H), 6.82 (d, J = 8.8 Hz, 2H), 6.40-6.19 (m, 2H), 3.79 (s, 3H), 3.61 (p, J = 6.9 Hz, 1H), 1.45 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ: 158.87, 146.00, 133.23, 130.45, 128.57, 127.93, 127.41, 127.34, 126.26, 113.99, 77.47, 77.15, 76.83, 55.40, 42.64, 21.44.

[0043] Example 5

[0044] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-4-(2-bromovinyl)benzoic acid methyl ester (72 mg, 0.3 mmol), (1 -chloroethyl)benzene (14.0 mg, 13 μL, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, placed on a stirrer with blue light illumination at a wavelength of 425 nm and allowed to react at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1 ) to give a colorless oil (20 mg, 75% yield, 82% ee). Optical rotation [a] D 25 = 31.1 (c = 0.45, CHCI3). NMR spectral data are as follows: 1 HNMR (400 MHz, CDCI3) δ: 7.95 (d, J = 8.3 Hz, 2H), 7.45-7.26 (m, 6H), 7.21 (d, J = 7.1 Hz, 1 H), 6.56-6.39 (m, 2H), 3.89 (s, 3H), 3.70-3.61 (m, 1 H), 1.48 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCI3) δ: 167.08, 145.16, 142.22, 138.21, 129.98, 128.64 (d, J = 9.2 Hz), 127.86, 127.40, 126.51, 126.11, 77.44, 77.12, 52.12, 42.81, 21.11.

[0045] Example 6

[0046] In an argon-filled glove box, the chiral ligand shown in Formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-2-(2-bromovinyl)thiophene (37.8 mg, 0.2 mmol), (1- chloroethyl)benzene (14.0 mg, 13 μL, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5- dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-benzenedicarbonitrile (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, and placed on a stirrer under a blue light with a wavelength of 425 nm, and allowed to react at room temperature for 24 h. After the reaction was completed, 5 mL of ethyl acetate was added to the reaction, and the mixture was washed with saturated brine (3 x 10 mL), and the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (16.1 mg, 75% yield, 88% ee). The specific optical rotation was [α] D 25 = -314.2 (c = 0.50, CHCl3). The nuclear magnetic resonance spectral data are as follows: 1 H NMR (400 MHz, CHCl3) δ: 7.36-7.28 (m, 3H), 7.27 (d, J = 1.4 Hz, 1H), 7.24-7.14 (m, 2H), 7.09 (d, J = 5.0 Hz, 1H), 7.04-6.97 (m, 1H), 6.96-6.85 (m, 2H), 6.52 (d, J = 15.7 Hz, 1H), 6.24 (dd, J = 15.7, 6.7 Hz, 1H), 3.61 (p, J = 6.5, 6.0 Hz, 1H), 1.45 (d, J = 7.0 Hz, 4H). 13 C{ 1 H}NMR (101 MHz, CDCl3) δ: 142.9, 135.2, 128.6, 127.9, 127.5, 127.4, 126.4, 124.9, 123.6, 122.0, 42.5, 21.2.

[0047] Example 7

[0048] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-(2-bromovinyl)benzene (36.6 mg, 0.2 mmol), 1-(1-chloroethyl)-4- (trifluoromethoxy)benzene (22.5 mg, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5- dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-benzenedicarbonitrile (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, placed on a stirrer with blue light illumination at a wavelength of 425 nm and allowed to react at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (21 mg, 72% yield, 81% ee). Optical rotation [a] D 25 = 4.2 (c = 1.05, CHCI3). NMR spectral data are as follows: 1 H NMR (400 MHz, CHCI3) δ: 7.39-7.26 (m, 7H), 7.24-7.13 (m, 4H), 6.49-6.18 (m, 2H), 3.66 (p, J = 6.9 Hz, 1H), 1.46 (d, J = 7.0 Hz, 3H). 13 C{ 1 H} NMR (101 MHz, CDCl3) δ: 147.6, 144.4, 137.4, 134.6, 129.0, 128.7, 127.4, 126.3, 121.2, 119.3, 42.1, 21.3. 19 F NMR (376 MHz, CDCl3): -57.78.

[0049] Example 8

[0050] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-(2-bromovinyl)benzene (36.6 mg, 0.2 mmol), 1 -chloro-4-(1 -chloroethyl)benzene (17.5 mg, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, placed on a stirrer with blue light illumination at a wavelength of 425 nm and allowed to react at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1 ) to give a colorless oil (12.3 mg, 55% yield, 83% ee). Optical rotation [a] D 25 = 11.6 (c = 0.24, CHCI3). NMR spectral data are as follows: 1 H NMR (400 MHz, CDCI3) δ: 7.37-7.26 (m, 6H), 7.19 (t, J = 7.0 Hz, 3H), 6.39 (d, J = 16.0 Hz, 1 H), 6.31 (dd, J = 15.9, 6.2 Hz, 1 H), 3.61 (p, J = 6.8 Hz, 1 H), 1.43 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCI3) δ: 144.16, 137.42, 134.68, 131.99, 129.00, 128.82, 128.67 (d, J = 2.7 Hz), 127.33, 126.27, 77.46, 77.14, 76.83, 42.05, 21.26.

[0051] Example 9

[0052] In an argon filled glove box, the chiral ligand shown in formula 3 (4.0 mg, 0.011 mmol) and bis-(1,5-cyclooctadiene)nickel (2.8 mg, 0.01 mmol) were added to 1 mL of dimethylsulfoxide, followed by the addition of (E)-(2-bromovinyl)benzene (36.6 mg, 0.2 mmol), 1-(1-chloroethyl)-4-methylbenzene (15.5 mg, 0.1 mmol), 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (38.0 mg, 0.15 mmol), N,N-dicyclohexylmethylamine (58.5 mg, 65 μL, 0.3 mmol), 2,4,5,6-tetra-(9-carbazolyl)-1,3-dicyanobenzene (4.0 mg, 0.005 mmol). The reaction vial was capped, removed from the glove box, placed on a stirrer with blue light at a wavelength of 425 nm, and allowed to react at room temperature for 24 h. After the reaction was complete, 5 mL of ethyl acetate was added to the reaction, washed with saturated brine (3 x 10 mL), the organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography on silica gel (eluted with petroleum ether:EtOAc = 100:1) to give a colorless oil (20 mg, 75% yield, 82% ee). The specific optical rotation [a] D 25 = 31.1 (c = 0.45, CHCI3). The nuclear magnetic resonance spectral data are as follows: 1 HNMR (400 MHz, CDCI3) δ: 7.34 (d, J = 7.2 Hz, 2H), 7.28 (d, J = 7.3 Hz, 1 H), 7.22-7.10 (m, 5H), 6.38 (d, J = 6.3 Hz, 2H), 3.64-3.55 (m, 1 H), 2.32 (s, 3H), 1.44 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCI3) δ: 142.72, 137.72, 135.56, 129.28, 128.58, 128.40, 127.28, 127.09, 126.36 (d, J = 25.7 Hz), 77.44, 77.13, 76.81, 42.25, 21.37, 21.11.

Claims

1. A method for synthesizing an (R)-1,3-diarylbutenyl compound, characterized by: Under the condition of visible light of 400-500 nm, a compound shown as formula 1 and a compound shown as formula 2 are used as raw materials, a chiral ligand shown as formula 3, a nickel catalyst, a photo catalyst, a reducing agent and a base are used to react to obtain an (R)-1,3-diaryl butenyl compound shown as formula 4: The base is selected from one or more of carbonates inorganic bases or tertiary amine organic bases; The nickel catalyst is selected from bis-(1,5-cyclooctadiene) nickel; The photo catalyst is selected from 2,4,5,6-tetra-(9-carbazolyl)-m-benzene dicarbonitrile; The reducing agent is selected from 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester; R 1 selected from hydrogen, halogen, ester, methyl, methoxy; R 2 selected from hydrogen, halogen, trifluoromethyl, trifluoromethoxy, naphthyl.

2. A method for synthesizing an (R)-1,3-diarylbutenyl compound, characterized by: Under the condition of visible light of 400-500 nm, a compound shown as formula 1 and a compound shown as formula 2 are used as raw materials, a chiral ligand shown as formula 3, a nickel catalyst, a photo catalyst, a reducing agent and a base are used to react to obtain an (R)-1,3-diaryl butenyl compound shown as formula 4: The base is selected from one or more of carbonates inorganic bases or tertiary amine organic bases; The nickel catalyst is selected from bis-(1,5-cyclooctadiene) nickel; The photo catalyst is selected from 2,4,5,6-tetra-(9-carbazolyl)-m-benzene dicarbonitrile; The reducing agent is selected from 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester.

3. The method of synthesis according to any one of claims 1 or 2, wherein The base is selected from N,N-dicyclohexylmethylamine, triethylamine, cesium carbonate, sodium carbonate.

4. The method of synthesis according to any one of claims 1 or 2, wherein The reaction is carried out in a solvent selected from one or more of dimethyl sulfoxide, N,N-dimethylformamide or dimethyl ether.

5. The method of synthesis according to any one of claims 1 or 2, wherein The molar ratio of the compound shown as formula 1, the compound shown as formula 2, the nickel catalyst, the chiral ligand shown as formula 3, the photo catalyst, the reducing agent and the base is (1-3):1:(0.1-1):(0.1-1):(0.01-1):(2-5):(2-5).

6. The method of synthesis according to any one of claims 1 or 2, wherein The molar ratio of the compound shown as formula 1, the compound shown as formula 2, the nickel catalyst, the chiral ligand shown as formula 3, the photo catalyst, the reducing agent and the base is 2:1:0.1:0.1:0.05:3:1.

5.

7. The method of synthesis according to any one of claims 1 or 2, wherein The reaction is carried out under blue light of 425 nm wavelength.

8. The method of synthesis according to any one of claims 1 or 2, wherein The synthesis method is carried out under nitrogen or argon protection.

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