A method for synthesizing alpha-tertiary carbon hyperallylic primary amine by nickel catalyzed non-activated olefin

Abstract

The application discloses a method for synthesizing alpha-tertiary carbon hyperallylic amine from non-activated olefin by nickel catalysis, which comprises the following steps: in an organic solvent, using metal nickel as a catalyst and metal manganese as a reducing agent, making imine and non-activated olefin to generate alpha-tertiary carbon hyperallylic primary amine through oxidative cyclization coupling. The application has the advantages of simple preparation of raw materials, cheap and easy purchase of catalyst and reducing agent, mild reaction condition, non-toxic and harmless, high reaction selectivity and yield, good compatibility of substrate functional groups and wide application range. The application can well realize the oxidative cyclization reaction of olefin and imine. Under the optimized reaction condition, the yield of the target product can be up to 92% after separation.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of catalytic synthesis and fine chemical synthesis, and relates to a method for synthesizing alpha-tertiary carbon homoallylic primary amine from non-activated olefin by nickel catalysis. BACKGROUND

[0002] Amine compounds exist widely in the biological world and have extremely important physiological effects. Most drug molecules contain amine functional groups. Homoallylic amine is a basic structural unit in numerous natural products, drug molecules and bioactive molecules. Meanwhile, it is an important synthetic intermediate and is involved in a series of synthetic transformations related to drug molecules and organic chemistry.

[0003] Homoallylic amine skeleton is a basic unit in organic synthesis, and its preparation has high industrial value. At present, pre-preparation of allyl metal reagent and then hydrolysis and protonation are effective ways to construct homoallylic amine compounds. However, the allyl metal reagent is sensitive to oxygen and humidity, and needs strict anhydrous and anaerobic and low-temperature environment. In addition, the allyl metal reagent has certain toxicity and is harmful to the environment, and is difficult to industrialize due to high cost. These characteristics limit the further development of the method. Alternatively, homoallylic amine compounds can also be prepared by the polarity inversion strategy of imine. For the preparation of homoallylic amine compounds, most of the existing technologies are to synthesize alpha-disubstituted amine compounds. In 2006, Jon A. Tunge reported the first example of palladium-catalyzed synthesis of protected alpha-secondary carbon homoallylic amine, which successfully avoided the use of allyl metal reagent. In 2019, Professor Amir H. Hoveyda developed a method for preparing alpha-secondary substituted chiral homoallylic amine compounds through a multi-component reaction. The reaction does not need any protection group modification and deprotection step, and can control the chelation state of the reaction intermediate by adjusting the reaction conditions, thereby stereodivergently synthesizing syn or anti configuration products. However, there are almost no reports on the synthesis of alpha-tertiary carbon homoallylic primary amine compounds by transition metal catalysis without using allyl metal reagent. SUMMARY

[0004] The application provides a method for synthesizing alpha-tertiary carbon homoallylic primary amine from non-activated olefin by nickel catalysis, which is a new method for synthesizing alpha-tertiary carbon homoallylic primary amine compounds with high yield.

[0005] The method of the application only needs one-step reaction, does not need participation of organic metal reagent, meanwhile has the advantages of easy preparation of raw material, cheap and easy purchase of catalyst and reducing agent, mild and non-toxic and harmless reaction condition, high reaction selectivity and yield, good compatibility of functional groups of substrates and wide application range, etc., and can synthesize various complex α-tertiary high allyl primary amine compounds.

[0006] Technical scheme: In order to achieve the above-mentioned purpose, the application provides a method for synthesizing α-tertiary carbon high allyl primary amine by using non-activated olefin and nickel catalysis, which comprises the following steps: in an organic solvent, using manganese as a reducing agent and nickel as a catalyst, imine is subjected to oxidative cyclization coupling with non-activated olefin to generate α-tertiary carbon high allyl primary amine, and the reaction general formula is as follows:

[0007]

[0008] In the formula, Ar1 and Ar2 each independently represent substituted or non-substituted aryl, biphenyl, naphthyl, anthracene or substituted or non-substituted N, O and S containing five to thirteen ring heteroaryl.

[0009] In the formula, Ar1 represents substituted or non-substituted aryl, substituted or non-substituted biphenyl, naphthyl, substituted or non-substituted anthracene, or substituted or non-substituted N, O and S containing five to thirteen ring heteroaryl, and the substituents on the benzene ring are selected from hydrogen, C1-C20 alkyl, C1-C20 halogen-substituted alkyl, C1-C20 alkylcarbonyl, nitro, hydroxyl, cyano, silicon, amino or sulfur.

[0010] In the formula, Ar2 represents substituted or non-substituted aryl, substituted or non-substituted biphenyl, naphthyl, substituted or non-substituted anthracene, or substituted or non-substituted N, O and S containing five to thirteen ring heteroaryl, and the substituents on the benzene ring are selected from hydrogen, C1-C20 alkyl, C1-C20 halogen-substituted alkyl, C1-C20 alkylcarbonyl, nitro, hydroxyl, cyano, silicon, amino or sulfur.

[0011] The nickel is nickel chloride, anhydrous nickel bromide, hydrated nickel bromide, nickel iodide, nickel carbonate, bis-(1,5-cyclooctadiene)nickel, nickel chloride ethylene glycol dimethyl ether complex, nickel bromide ethylene glycol dimethyl ether complex, (2,2'-bipyridine) nickel dibromide, nickel dibromide (1,10-phenanthroline), nickel chloride bis-trihexylphosphonium salt, bis(triphenylphosphine) nickel chloride, 1,2-bis(diphenylphosphino)ethane nickel chloride, (1,1'-bis(diphenylphosphino) ferrocene) nickel dichloride, nickel bromide diethylene glycol dimethyl ether complex, nickel acetylacetonate, nickel trifluoromethanesulfonate, bis(2,2,6,6,-tetramethyl-3,5-heptanedionate) nickel, bis(hexafluoroacetylacetonate) nickel, nickel perchlorate, nickel p-toluenesulfonate, 1,3-bis(diphenylphosphinopropane) nickel dichloride, nickel tetrafluoroborate hexahydrate, bis(triphenylphosphine) nickel dibromide or dibromobis(tri-n-butylphosphine) nickel.

[0012] Preferably, the nickel is nickel chloride, anhydrous nickel bromide, hydrated nickel bromide or nickel tetrafluoroborate hexahydrate.

[0013] More preferably, the nickel is nickel chloride.

[0014] The organic solvent is selected from any one of methanol, ethanol, ethylene glycol, n-propanol, isopropanol, 1,3-propanediol, glycerol, n-butanol, isobutyl alcohol, tert-butyl alcohol, trifluoroethanol, 2-methyl-2-butanol, 3-methoxybutanol, sec-butyl alcohol, tert-amyl alcohol, 4-methyl-2-pentanol, isoamyl alcohol, 2-pentanol, 3-pentanol, cyclopentanol, n-pentanol, polyethylene glycol 200-10000, acetonitrile, benzonitrile, toluene, acetone, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dimethylformamide, N,N-diacetamide, N,N-dimethylacrylurea, N-methylpyrrolidone, ethyl acetate, 1,4-dioxane or tetrahydrofuran.

[0015] Preferably, the organic solvent is selected from methanol, ethanol, N,N-dimethylformamide, N,N-diacetamide, N,N-dimethylacrylurea or N-methylpyrrolidone.

[0016] The molar ratio of the olefin, imine, nickel and manganese is 1:(1-2):(0.1-0.2):(3-4).

[0017] The reaction temperature is 40-60°C and the reaction time is 24-48 hours.

[0018] The reaction is carried out in an atmosphere of inert gas.

[0019] The nickel catalyst in the method has the characteristics of wide source and low price, the olefin with a directing group is used in the reaction process to coordinate with the nickel catalyst to form a high-activity catalytic species, and the catalytic species reacts with imine under the joint action of a reducing agent manganese and a solvent to form an oxidized cyclization reaction, the reaction has high activity and selectivity. In addition, the method solves the limitation that metal format reagents are required in the reaction.

[0020] The amine group is introduced on the olefin for the preparation of amine compounds for the first time, and through the screening and establishment of experimental conditions, the alpha-high allyl tertiary amine compounds are synthesized through the nickel catalysis, Mn reduction and oxidation cyclization mechanism. Different from the prior art, the transition metal catalysis is used for the first time to successfully synthesize the alpha-high allyl tertiary amine compounds with high steric hindrance. In the preparation process, the use of organic metal reagents is avoided, the substrate functional group has good compatibility and wide application range. The application provides a method for synthesizing alpha-tertiary carbon high allyl primary amine by using inexpensive nickel to catalyze non-activated olefin, the method has high yield and avoids the use of organic metal reagents, and meets the concept of green chemistry.

[0021] The synthesis method of the application first selects a specific olefin, and the end olefin with a guiding function is used. Different from the nickel catalysis in the prior art, the non-activated olefin difunctionalization is realized, the alpha-high allyl amine compounds are synthesized, the amination of the olefin is realized, and in addition, the application is a reaction of non-activated olefin and oxime ester under nickel catalysis, instead of the coupling between the non-end olefin with a guiding function and the halogenated hydrocarbon in the prior art.

[0022] Advantages: compared with the prior art, the application has the following advantages:

[0023] (1) The application provides a synthesis method of alpha-tertiary carbon high allyl primary amine compounds, which only needs one-step reaction and avoids the participation of organic metal reagents; the reaction condition is mild, the selectivity is high, the yield is high, the substrate functional group has good compatibility, and the application range is wide;

[0024] (2) The synthesis method provided by the application is simple, safe and environmentally friendly, and alpha-tertiary carbon high allyl primary amine compounds are directly obtained by one-step method, under the optimized reaction conditions, the yield of the target product after separation can be as high as 92%, which is a universal, efficient, economic and environmentally friendly method for synthesizing alpha-tertiary carbon high allyl primary amine compounds;

[0025] (3) The specific synthetic method of the present application can use ideal nickel as catalyst for two-component catalytic reaction, which is not only due to the particularity of the whole reaction system, but also due to the use of olefins with directing groups in the reaction system, so that the reaction can be carried out under very mild conditions for the oxidative cyclization of olefins and imines, and ideal catalytic effect can be obtained for complex substrates.

[0026] (4) The α-tertiary carbon homoallyl amine compound synthesized by the method of the present application can be used as a drug or a bioactive molecule, and is also an important organic intermediate, which is widely used in the synthesis of drug molecules and natural compounds. DETAILED DESCRIPTION

[0027] The present application can be better understood according to the following examples. However, it is easy for those skilled in the art to understand that the content described in the examples is only for illustrating the present application, and should not and will not limit the present application described in detail in the claims.

[0028] The experimental methods described in the examples are all conventional methods unless otherwise specified; the reagents and materials described are all commercially available or can be simply prepared by the following methods unless otherwise specified.

[0029] Some of the initial substrates are synthesized by the following methods or commercially available, and the rest of the substrates are reported or commercially available or synthesized by reference to the following methods.

[0030]

[0031] Among them, Ar1, Ar2 and the substituents on the final substrate product are the same.

[0032] First step: In a 100 mL round-bottom flask equipped with a condenser, the aromatic ketone (10.0 mmol, 1.0 equiv) was dissolved in a mixture of ethanol / water (v / v = 4 / 1). Then, NH2OH . HCl (1.39 g, 20.0 mmol, 2.0 equiv) and NaOAc (1.64 g, 20.0 mmol, 2.0 equiv) were added. The reaction mixture was refluxed overnight, and the consumption of the starting material was observed by TLC. After the reaction was completed, the reaction was cooled to room temperature and concentrated under reduced pressure to remove ethanol as much as possible. Then the white solid was diluted with water, extracted with ethyl acetate, and dried over anhydrous Na2SO4. The product was directly used for the preparation of oxime ester.

[0033] Second step: To the oxime (4.0 mmol, 1.0 equiv) in dry dichloromethane (20 mL) was added at room temperature C6F5COOH (1.27 g, 6.0 mmol, 1.5 equiv), DMAP (48.9 mg, 0.4 mmol, 0.1 equiv), EDCI (1.15 g 6.0 equiv, 1.5 equiv) successively. The resulting mixture was stirred for 0.5 h. When all the oxime was consumed (TLC monitoring), the mixture was quenched with water and extracted with DCM (3 x 10 mL). The resulting organic layer was washed with brine and dried over anhydrous Na2S04. Purification was performed by silica gel column chromatography (eluent: petroleum ether: ethyl acetate V / V = 10: 1) to give the pure oxime ester.

[0034]

[0035] Substrate one:

[0036] 1 H NMR (400 MHz, CDC13): δ 7.71 - 7.58 (m, 2H), 7.52 - 7.47 (m, 4H), 7.40 - 7.33 (m, 4H). Other spectra are reported in the corresponding literature.

[0037]

[0038] Substrate two:

[0039] 1 H NMR (400 MHz, CDC13): δ 7.51 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 6.6 Hz, 4H), 7.24 - 7.19 (m, 2H), 2.43 (s, 3H), 2.41 (s, 3H). Other spectra are reported in the corresponding literature.

[0040]

[0041] Substrate three:

[0042] 1 H NMR (400 MHz, CDC13): δ 7.56 (d, J = 8.9 Hz, 2H), 7.31 (d, J = 8.8 Hz, 2H), 6.99 - 6.93 (m, 2H), 6.92 - 6.88 (m, 2H), 3.86 (s, 3H), 3.85 (s, 3H). Other spectra are reported in the corresponding literature.

[0043]

[0044] Substrate four:

[0045] 1 H NMR (400 MHz, CDC13): δ 7.66-7.57 (m, 2H), 7.40-7.32 (m, 2H), 7.21-7.14 (m, 2H), 7.10 (t, J = 8.6 Hz, 2H). Other spectra are reported in the corresponding literature.

[0046]

[0047] Substrate five:

[0048] 1 H NMR (400 MHz, CDC13): δ 7.56 (d, J = 8.6 Hz, 2H), 7.46 (d, J = 8.5 Hz, 2H), 7.39 (d, J = 8.6 Hz, 2H), 7.33-7.22 (m, 2H). Other spectra are reported in the corresponding literature.

[0049]

[0050] Substrate six:

[0051] 1 H NMR (400 MHz, CDC13): δ 7.62 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.7 Hz, 2H), 7.51-7.47 (m, 2H), 7.23-7.16 (m, 2H). 13 C NMR (100 MHz, CDC13): δ 165.05, 156.47, 144.26, 139.08, 136.57, 132.61, 132.12, 131.92, 130.72, 130.44, 130.37, 130.32, 126.77, 124.98, 106.63. 19 F NMR (376 MHz, CDC13): δ -137.09 (dt, J = 20.3, 6.1 Hz), -147.02 (d, J = 4.5 Hz), -157.21 - -161.26 (m). HRMS (ESI): Calcd for C13H10Br2NO+, [M+H2O-C6F5COO-]: 353.9124; Found: 355.9107.

[0052]

[0053] Substrate seven:

[0054] 11H NMR (400 MHz, CDCl3): δ 7.71–7.55 (m, 2H), 7.47 (ddt, J = 5.1, 3.4, 2.0 Hz, 1H), 7.43–7.34 (m, 2H), δ 6.91 (d, J = 2.6 Hz, 3H), 3.92 (d, J = 2.9 Hz, 3H), 3.82 (d, J = 2.1 Hz, 3H). 13 13C NMR (100 MHz, CDCl3): δ 166.70, 166.68, 156.76, 150.49, 148.52, 146.67, 146.60, 146.54, 144.85, 144.72, 144.10, 144.03, 143.98, 142.26, 142.13, 139.15, 139.01, 138.95, 138.88, 138.82, 136.64, 136.58, 136.51, 136.45, 136.30, 134.47, 131.44, 129.52, 128.54, 124.17, 122.64, 112.20, 110.53, 107.29, 107.16, 106.96, 55.96, 55.89. 19 19F NMR (376 MHz, CDCl3): δ -137.37 (dq, J = 20.8, 5.9, 5.5 Hz), -147.83 (ddd, J = 21.2, 16.3, 5.2 Hz), -155.61– -162.72 (m). HRMS (ESI): Calcd for C15H16NO3+, [M + H2O - C6F5COO-]: 258.1125; Found: 258.1129.

[0055]

[0056] Substrate Eight

[0057] 1 1H NMR (400 MHz, CDCl3): δ 8.02 (s, 1H), 7.84 (d, J = 1.7 Hz, 2H), 7.70–7.54 (m, 3H), 7.46 (t, J = 7.7 Hz, 2H). 1313C NMR (100 MHz, CDCl3): δ 163.85, 155.93, 146.98, 145.25, 139.21, 136.70, 134.10, 132.78, 132.61, 132.49, 132.44, 132.11, 131.77, 129.21, 129.18, 129.14, 127.05, 124.34, 124.13, 124.09, 124.06, 124.02, 121.63, 118.91, 106.26. 19 19F NMR (376 MHz, CDCl3): δ -63.08, -137.14 (dt, J = 19.9, 6.4 Hz), -142.90 – -151.90 (m), -156.49 – -165.31 (m). HRMS (ESI): Calcd for C15H10F6NO+, [M + H2O - C6F5COO-]: 334.0661; Found: 334.0666.

[0058]

[0059] Substrate Nine:

[0060] 1 1H NMR (400 MHz, CDCl3): δ 7.70 – 7.64 (m, 1.31H), 7.64 – 7.59 (m, 0.35H), 7.50 (dddd, J = 8.6, 7.3, 4.9, 1.7 Hz, 1.76H), 7.46 – 7.39 (m, 2.72H), 7.30 – 7.17 (m, 2.57H), 7.10 (ddd, J = 10.4, 8.3, 1.1 Hz, 0.29H). 13 13C NMR (100 MHz, CDCl3): δ 166.19, 165.25, 156.39, 152.79, 151.37, 150.08, 150.01, 144.90, 144.26, 142.31, 139.03, 138.91, 136.88, 136.52, 136.33, 132.68, 131.81, 131.05, 130.35, 129.16, 129.02, 128.78, 128.26, 125.37, 124.49, 124.41, 124.37, 106.72. 1919F NMR (376 MHz, CDCl3): δ -110.68–-110.91 (m), -111.26 (dt, J = 10.0, 5.4 Hz), -135.75–-139.74 (m), -145.98–-149.12 (m), -157.73–-161.79 (m). HRMS (ESI): Calcd for C13H11FNO+, [M + H2O - C6F5COO-]: 216.0819; Found: 216.0823.

[0061]

[0062] Substrate Ten:

[0063] 1 1H NMR (400 MHz, CDCl3): δ 7.66–7.54 (m, 2H), 7.53–7.42 (m, 1H), 7.42–7.34 (m, 2H), 7.26 (d, J = 1.2 Hz, 4H), 2.41 (s, 3H). 13 13C NMR (100 MHz, CDCl3): δ 167.09, 156.83, 146.77, 146.73, 146.70, 146.67, 146.61, 146.54, 146.50, 144.83, 144.75, 144.70, 144.65, 144.57, 144.20, 144.16, 144.13, 144.09, 144.04, 143.97, 142.25, 142.17, 142.14, 142.12, 142.07, 141.98, 140.45, 139.15, 139.10, 139.00, 138.94, 138.87, 138.81, 136.63, 136.57, 136.49, 136.44, 136.36, 136.33, 136.29, 134.41, 132.23, 131.41, 131.18, 131.14, 129.93, 129.42, 129.33, 129.24, 129.20, 129.04, 129.01, 128.98, 128.77, 128.72, 128.67, 128.53, 128.29, 107.32, 107.19, 107.15, 107.03, 106.99, 21.50. 19F NMR (376MHz, CDCl3): δ-137.24 (qd, J=12.5, 7.9, 6.7Hz), -148.04 (d, J=18.7Hz), -160.01 (ddq, J=20.7, 14.6, 7.0Hz). HRMS (ESI): Calcd for C 14 H 14 NO + ,[M+H2O-C6F5COO - ]:212.1070; Found:212.1077.

[0064]

[0065] Substrate 11:

[0066] 1 H NMR (400MHz, CDCl3): δ7.68–7.59(m,2H),7.51–7.45(m,1H),7.38(td,J=7.6,1.7Hz,3H),7.33–7.28(m,2H),7.13(d,J=7.5Hz,1H),2.18(s,3H). 13 CNMR (100MHz, CDCl3): δ167.24,156.73,146.80,146.74,146.68,146.62,144.89,144.81,144.76,144.71,144.63,144. 27,144.23,144.17,144.11,144.05,142.30,142.22,142.17,142.12,142.04,139.13,139.08,138.97,138.92,138.85, 138.78,136.61,136.55,136.47,136.42,136.27,135.17,133.16,132.46,131.70,131.17,130.73,130.64,130.34,130.29,129.56,129.50,128.80,128.67,128.51,128.36,127.25,125.96,125.83,107.06,106.94,106.89,106.76,19.48. 1919F NMR (376 MHz, CDCl3) δ -137.25 (ddt, J = 20.4, 12.1, 6.3 Hz), -147.93 (dt, J = 20.7, 5.1 Hz), -160.06 (dtt, J = 20.4, 14.3, 7.1 Hz). HRMS (ESI): Calcd for C 14 H 14 NO + , [M + H2O - C6F5COO - : 212.1070; Found: 212.1070.

[0067]

[0068] Substrate Twelve:

[0069] 1 1H NMR (400 MHz, CDCl3): δ 7.67–7.53 (m, 2.71H), 7.53–7.39 (m, 4.24H), 7.37–7.30 (m, 2.72H), 7.05–6.82 (m, 2.78H), 3.87 (s, 1.1H), 3.85 (s, 3H). 13 13C NMR (100 MHz, CDCl3): δ 166.77, 166.69, 162.43, 161.06, 156.87, 146.74, 146.67, 146.62, 144.81, 144.72, 144.68, 144.16, 144.10, 144.04, 142.23, 142.14, 142.09, 139.13,  138.97, 138.90, 138.84, 136.60, 136.55, 136.47, 136.31, 134.69, 132.34, 131.37, 131.24, 130.99, 129.89, 129.61, 128.62, 128.55, 128.41, 128.31, 126.22, 123.97, 114.01, 113.63, 107.10. 19 19F NMR (376 MHz, CDCl3): δ -137.25 (dd, J = 14.2, 4.9 Hz), -146.72– -149.46 (m), -158.48– -161.10 (m). HRMS (ESI): Calcd for C 21 H 13 F5NO3, [M + H] + : 422.0810; Found: 422.0815.

[0070]

[0071] Substrate Thirteen:

[0072] 1 H NMR (400MHz, CDCl3): δ7.89–7.58(m,6H),7.58–7.34(m,8H). 13 C NMR (100MHz, CDCl3): δ166.83,166.79,156.82,146.69,144.77,144.33,144.12,144.02 ,142.95,142.19,140.02,139.98,139.17,139.00,138.83,136.65,136.46,134.19,132. 86,132.07,131.60,130.78,130.11,129.80,129.58,129.47,129.05,129.02,128.75,128.68,128.64,128.43,128.14,128.10,127.26,127.23,127.21,126.94,107.09,107.04. 19 F NMR (376MHz, CDCl3): δ-137.13 (ddd, J=22.4, 14.3, 4.9Hz), -147.73 (d, J=4.8Hz), -159.85 (ddd, J=41.0, 20.6, 14.3Hz). HRMS (ESI): Calcd for C 19 H 16 NO + ,[M+H2O-C6F5COO - ]:274.1226;Found:274.1233.

[0073]

[0074] Substrate Fourteen:

[0075] 1 H NMR (400MHz, CDCl3): δ7.67–7.55(m,2H),7.55–7.35(m,5H),7.35–7.21(m,2H). 1313C NMR (100 MHz, CDCl3): δ 166.02, 165.91, 156.58, 146.83, 146.71, 144.89, 144.85, 144.20, 144.14, 142.35, 142.30, 142.26, 139.17, 139.06, 139.01, 138.93, 138.87, 137.92, 136.63, 136.51, 136.47, 136.33, 133.72, 132.58, 131.78, 131.59, 130.58, 130.36, 130.33, 129.27, 129.09, 128.94, 128.88, 128.76, 128.74, 128.69, 128.59, 128.50, 106.95, 106.83, 106.79, 106.66. 19 19F NMR (376 MHz, CDCl3): δ -136.43–-137.69 (m), -146.07–-147.99 (m), -159.13–-160.89 (m). HRMS (ESI): Calcd for C 13 H 10 Br2NO + , [M + H2O - C6F5COO - : 352.0524; Found: 232.0526.

[0076]

[0077] Substrate XV:

[0078] 1 1H NMR (400 MHz, CDCl3): δ 7.64–7.58 (m, 1.49H), 7.57–7.45 (m, 4.69H), 7.41 (dd, J = 8.3, 7.0 Hz, 0.85H), 7.35–7.30 (m, 1.22H), 7.23 (d, J = 8.4 Hz, 0.83H). 13C NMR (100MHz, CDCl3): δ166.13,165.95,156.60,146.77,144.91,144.87,144.21,144.1 0,142.33,142.28,142.19,139.18,139.02,138.90,136.53,136.37,133.65,133.05,1 31.94, 131.82, 131.73, 131.53, 130.85, 130.78, 130.70, 130.50, 130.35, 129.35, 129.28, 128.76, 128.72, 128.64, 128.52, 128.38, 126.45, 124.66, 106.96, 106.81, 106.66. 19 F NMR(376MHz, CDCl3): δ-134.90–-139.11(m),-147.35(dtt,J=42.0,21.0,4.8Hz),-158.37–-160.45(m).HRMS(ESI):Calcd for C 13 H 11 BrNO + ,[M+H2O-C6F5COO - ]:276.0019;Found:276.0019.

[0079] In the examples, olefin 2 was used as raw material, which is a known compound.

[0080] The specific structures of the substrates and products in the embodiments are shown in Table 1.

[0081] Example 1

[0082] Synthesis of Compound 1

[0083] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1a (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 1 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 81% yield. 1H NMR (400MHz, CDCl3): δ9.83(s,1H),8.97–8.71(m,2H),8.15(dt,J=8.3,1.5Hz,1H),7.59–7.38(m,7H),7.33(dd,J=8.5,6.8Hz ,4H),7.28–7.18(m,2H),6.86(dt,J=15.0,7.4Hz,1H),6.27(dd,J=15.2,1.5Hz,1H),3.23(dd,J=7.5,1.4Hz,2H),1.87(s,2H). 13 C NMR (100MHz, CDCl3): δ163.65,148.25,147.80,141.56,138.55,136.51,134.62,128.61,128. 46,128.04,127.57,126.85,126.63,121.76,121.72,116.81,61.03,46.06.HRMS(ESI):Calcd for C 26 H 24 N3O[M+H] + Found: 394.1914; Found: 394.1907.

[0084] Example 2

[0085] Synthesis of Compound 2

[0086] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1b (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added, and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 2 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 86% yield. 1 H NMR (400MHz, CDCl3): δ9.82(s,1H),8.93–8.68(m,2H),8.14(dd,J=8.3,1.7Hz,1H),7.54–7.42(m,3H),7.33–7.26(m,4H),7.19– 7.07(m,4H),6.87(dt,J=15.0,7.4Hz,1H),6.26(dt,J=15.2,1.4Hz,1H),3.20(dd,J=7.5,1.4Hz,2H),2.33(s,6H),1.99(s,2H).13 C NMR (100MHz, CDCl3): δ163.68,148.19,145.01,141.87,138.53,136.45,136.27,134.64,129.08, 128.38,128.01,127.53,126.47,121.71,121.64,116.78,60.59,46.12,21.04.HRMS(ESI):Calcd for C 28 H 28 N3O[M+H] + :422.2227;Found:422.2219.

[0087] Example 3

[0088] Synthesis of Compound 3

[0089] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1c (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 3 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 46% yield. 1 H NMR (400MHz, CDCl3): δ9.83(s,1H),8.79(dt,J=6.5,1.7Hz,2H),8.15(dd,J=8.3,1.7Hz,1H),7.75–7.39(m,3H),7.31(d ,J=8.9Hz,4H),7.07–6.67(m,5H),6.26(dt,J=15.2,1.4Hz,1H),3.79(s,6H),3.18(dd,J=7.4,1.3Hz,2H),2.10(s,2H). 13 C NMR (100MHz, CDCl3): δ163.70,158.28,148.24,141.83,140.14,138.53,136.49,134.62,128.42, 128.02,127.73,127.54,121.75,121.70,116.80,113.67,60.23,55.35,46.32.HRMS(ESI):Calcd for NaC 28 H 27 N3O3,[M+Na]+ Found: 476.1944; Found: 476.1952.

[0090] Example 4

[0091] Synthesis of Compound 4

[0092] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1d (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 4 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 73% yield. 1 H NMR (400MHz, CDCl3): δ9.83(s,1H),9.13–8.64(m,2H),8.16(dd,J=8.2,1.7Hz,1H),7.57–7.43(m,3H),7.40–7.31(m,4H) ,7.06–6.95(m,4H),6.80(dt,J=15.0,7.4Hz,1H),6.26(dt,J=15.1,1.4Hz,1H),3.18(dd,J=7.5,1.4Hz,2H),1.86(s,2H). 13 C NMR (100MHz, CDCl3): δ163.45,162.93,160.48,148.29,143.41,143.38,140.85,138.53,136.55, 134.52,129.06–127.39(m),128.05,121.84,121.81,116.86,115.27(d,J=21.2Hz),60.34,46.23. 19 F NMR(376MHz,CDCl3):δ-111.77–-123.36(m).HRMS(ESI):Calcd for C 26 H 22 F2N3O[M+H] + :430.1726; Found:430.1723.

[0093] Example 5

[0094] Synthesis of Compound 5

[0095] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1e (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added, and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 5 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 61% yield. 1 H NMR (400MHz, CDCl3): δ9.84(s,1H),9.02–8.53(m,2H),8.17(dd,J=8.3,1.7Hz,1H),7.56–7.49(m,2H),7.46(dd,J=8.3,4.2Hz ,1H),7.36–7.27(m,8H),6.79(dt,J=15.0,7.4Hz,1H),6.26(dt,J=15.2,1.3Hz,1H),3.17(dd,J=7.5,1.4Hz,2H),1.76(s,2H). 13 C NMR (100MHz, CDCl3): δ163.38,148.31,145.89,140.52,138.54,136.57,134.50,132.96, 129.09,128.70,128.04,127.58,121.88,121.83,116.88,60.46,45.85.HRMS(ESI):Calcd for C 26 H 22 Cl2N3O[M+H] + :462.1135; Found:462.1125.

[0096] Example 6

[0097] Synthesis of Compound 6

[0098] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1f (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added, and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 6 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 57% yield. 1H NMR (400MHz, CDCl3): δ9.84(s,1H),8.86–8.67(m,2H),8.16(dd,J=8.2,1.7Hz,1H),7.57–7.49(m,2H),7.49–7.40(m,5H) ,7.34–7.09(m,4H),6.79(dt,J=15.0,7.4Hz,1H),6.26(dt,J=15.1,1.4Hz,1H),3.16(dd,J=7.4,1.3Hz,2H),1.80(s,2H). 13 C NMR (100MHz, CDCl3): δ163.35,148.32,146.33,140.45,138.53,136.56,134.48,131.65,129. 12,128.40,128.05,127.57,121.88,121.82,121.15,116.88,60.57,45.69.HRMS(ESI):Calcd for C 26 H 22 Br2N3O[M+H] + :550.0124; Found:550.0122.

[0099] Example 7

[0100] Synthesis of Compound 7

[0101] In a glove box under nitrogen atmosphere, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate (1 g, 0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 7 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) under nitrogen atmosphere, with a yield of 61%. 1 H NMR (400MHz, CDCl3): δ9.83(s,1H),8.88–8.55(m,2H),8.15(dd,J=8.2,1.7Hz,1H),7.58–7.37(m,5H),7.32(dd,J=8.5,6.9Hz,2H) ,7.28–7.12(m,1H),7.05–6.75(m,4H),6.28(d,J=15.3Hz,1H),3.86(s,3H),3.81(s,3H),3.21(dd,J=7.5,1.3Hz,2H),1.90(s,2H).13 C NMR (100MHz, CDCl3): δ163.64,148.78,148.25,147.89,147.85,141.64,140.33,138.53,136.51,134.59,128.55,128.45,128 .03,127.55,126.85,126.51,121.76,121.73,118.74,116.81,110.68,110.45,60.84,56.02,55.96,46.24.HRMS(ESI):Calcd for C 28 H 28 N3O3[M+H] + :454.2125;Found:454.2123.

[0102] Example 8

[0103] Synthesis of Compound 8

[0104] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1h (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 8 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 35% yield. 1 H NMR (400MHz, CDCl3): δ9.85(s,1H),8.89–8.69(m,2H),8.16(dd,J=8.3,1.6Hz,1H),7.95(s,2H),7.76(s,1H),7.60–7.33(m,7H),7.29(d,J =7.0Hz,1H),6.81(dt,J=15.0,7.4Hz,1H),6.31(d,J=15.1Hz,1H),3.32(dd,J=14.1,7.2Hz,1H),3.21(dd,J=14.1,7.7Hz,1H),1.92(s,2H). 13C NMR (100MHz, CDCl3): δ163.18, 150.69, 148.31, 145.82, 139.81, 138.53, 136.55, 134.44, 131.68 (q, J = 33.2Hz), 129.63, 12 9.03,128.05,127.64,127.54,126.98,126.29,124.83,122.12,121.93,121.82,121.32–120.81(m),116.91,60.92,45.8. 19 F NMR(376MHz,CDCl3):δ-62.63.HRMS(ESI):Calcd forC 28 H 22 F6N3O[M+H] + :530.1662; Found:530.1655.

[0105] Example 9

[0106] Synthesis of Compound 9

[0107] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1i (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 9 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 56% yield. 1 H NMR (400MHz, CDCl3): δ9.82(s,1H),8.92–8.67(m,2H),8.13(dd,J=8.3,1.7 Hz,1H),7.61(d,J=1.8Hz,1H),7.56–7.17(m,10H),6.98(ddd,J=12.2,8.0, 1.4Hz,1H),6.87(dd,J=15.0,7.5Hz,1H),6.27(d,J=15.2Hz,1H),3.38(ddd ,J=13.9,7.2,1.4Hz,1H),3.14(ddd,J=13.9,7.6,1.3Hz,1H),2.12(s,2H). 13C NMR (100MHz, CDCl3): δ163.55,161.89,159.43,148.19,147.01,141.13,13 8.47,136.43,134.66(d,J=10.6Hz),134.55,129.14(d,J=8.8Hz),128.51, 128.35,127.96,127.66(d,J=4.0Hz),126.94,125.83,124.09(d,J=3.5Hz) ,121.70,121.68,116.75,116.51,59.70(d,J=1.5Hz),44.38(d,J=2.7Hz). 19 F NMR (376MHz, CDCl3): δ-110.09 (td, J = 8.1, 4.1Hz). HRMS (ESI): Calcd for C 26 H 23 FN3O[M+H] + :412.1820;Found:412.1812.

[0108] Example 10

[0109] Synthesis of Compound 10

[0110] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1j (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added, and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 10 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 74% yield. 1 H NMR (400MHz, CDCl3): δ9.82(s,1H),9.04–8.53(m,2H),8.14(dd,J=8.3,1.7Hz,1H),7.56–7.37(m,5H),7.38–7.27(m,4H),7.25–7.20(m, 1H),7.13(d,J=8.1Hz,2H),6.86(dt,J=15.0,7.4Hz,1H),6.27(d,J=15.1Hz,1H),3.21(dd,J=7.4,1.4Hz,2H),2.33(s,3H),2.00(s,2H). 13C NMR (100MHz, CDCl3): δ163.67,148.22,147.93,144.85,141.70,138.55,136.48,136.38,134.64,129.13,128.50, 128.41,128.03,127.54,126.76,126.59,126.51,121.73,121.67,116.80,60.83,46.08,21.05.HRMS(ESI):Calcd for NaC 27 H 25 N3O[M+Na] + Found: 430.1890; Found: 430.1892

[0111] Example 11

[0112] Synthesis of Compound 11

[0113] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1K (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 11 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 34% yield. 1 H NMR (400MHz, CDCl3): δ9.81 (s, 1H), 8.86–8.73 (m, 2H), 8.14 (dd, J = 8.3, 1.7Hz, 1H), 7.73 (dd ,J=7.8,1.5Hz,1H),7.59–7.39(m,3H),7.32–7.27(m,5H),7.21(ddd,J=8.8,5.8,2.6Hz,2H), 7.10(dd,J=7.5,1.6Hz,1H),6.82(dt,J=14.9,7.4Hz,1H),6.21(dt,J=15.3,1.5Hz,1H),3.28 (ddd,J=13.6,7.4,1.4Hz,1H),3.16(ddd,J=13.6,7.4,1.4Hz,1H),1.99(s,2H),1.93(s,3H). 13C NMR (100MHz, CDCl3): δ163.68,148.21,147.88,144.92,141.67,138.54,136.79,136.47,134.63,133.00,128.43,128.34, 128.02,127.54,127.39,126.56,126.16,126.05,125.78,121.73,121.66,116.80,61.26,45.98,21.86.HRMS(ESI):Calcd for C 27 H 26 N3O[M+H] + :408.2071; Found:408.2077.

[0114] Example 12

[0115] Synthesis of Compound 12

[0116] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1L (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 12 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 92% yield. 1 H NMR (400MHz, CDCl3): δ9.83 (s, 1H), 8.79 (dt, J=5.1, 1.5Hz, 2H), 8.14 (dd, J=8.3, 1.7Hz, 1H), 7.59–7.37 (m, 5H), 7.36–7.2 9(m,4H),7.25–7.18(m,1H),6.97–6.71(m,3H),6.44–6.16(m,1H),3.79(s,3H),3.21(dd,J=7.4,1.3Hz,2H),2.17(s,2H). 13C NMR (100MHz, CDCl3): δ163.66,158.31,148.23,147.92,141.65,139.83,138.51,136.48,134.59,128.52,128.42, 128.00,127.78,127.53,126.79,126.54,121.74,121.70,116.79,113.68,60.64,55.34,46.11.HRMS(ESI):Calcd for C 27 H 26 N3O2[M+H] + :424.2020; Found:424.2018.

[0117] Example 13

[0118] Synthesis of Compound 13

[0119] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1M (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 13 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 74% yield. 1 H NMR (400MHz, CDCl3): δ9.86 (s, 1H), 8.96–8.64 (m, 2H), 8.12 (dd, J = 8.3, 1.7Hz, 1H), 7.65–7.53 (m, 4H), 7.53–7.40 (m, 9H), 7.40–7. 31(m,3H),7.30–7.22(m,1H),6.93(dt,J=14.9,7.4Hz,1H),6.29(dd,J=15.2,1.5Hz,1H),3.26(dd,J=7.5,1.4Hz,2H),2.07(s,2H). 13C NMR (100MHz, CDCl3): δ163.56,148.17,147.62,146.81,141.45,140.69,139.51,138.44,136.40,134.54,128.80,128.60, 128.44,127.93,127.46,127.29,127.10,127.06,127.02,126.84,126.55,121.67,116.74,60.84,45.96.HRMS(ESI):Calcd for C 32 H 28 N3O, [M+H] + :470.2227;Found:470.2216.

[0120] Example 14

[0121] Synthesis of Compound 14

[0122] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1n (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 14 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 73% yield. 1 H NMR (400MHz, CDCl3): δ9.83(s,1H),8.83–8.69(m,2H),8.14(dd,J=8.3,1.7Hz,1H),7.56–7.42(m,3H),7.41–7.32(m ,5H),7.31–7.21(m,4H),6.83(dt,J=15.0,7.4Hz,1H),6.26(dd,J=15.2,1.5Hz,1H),3.31–2.99(m,2H),1.98(s,2H). 13CNMR (100MHz, CDCl3): δ163.48,148.24,147.36,146.26,141.01,138.49,136.49,134.52,132.65,128.80,128 .57,128.49,128.16,128.00,127.52,127.04,126.45,121.77,121.76,116.82,60.72,45.86.HRMS(ESI):Calcd for C 26 H 23 ClN3O[M+H] + :428.1524; Found:428.1519.

[0123] Example 15

[0124] Synthesis of Compound 15

[0125] Under a nitrogen atmosphere in a glove box, nickel chloride (0.03 mmol), olefin (0.3 mmol), substrate 1O (0.45 mmol), manganese (1.2 mmol), and N,N-dimethylformamide (1.2 mL) were added sequentially to a 10 mL reaction flask. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 48 h. After the reaction was complete, 1 mL of water was added, and the mixture was stirred for 1 h. Immediately afterwards, the mixture was extracted with ethyl acetate (5 mL x 3), the organic phases were combined, the solvent was removed under reduced pressure, and the product compound 15 was separated by column chromatography (eluent: dichloromethane:methanol V / V = 30:1) in 64% yield. 1 H NMR (400MHz, CDCl3): δ9.83(s,1H),8.89–8.67(m,2H),8.15(dd,J=8.2,1.7Hz,1H),7.57–7.47(m,2H),7.47–7.41(m,3H),7. 40–7.27(m,6H),7.23(d,J=7.1Hz,1H),6.82(dt,J=15.0,7.4Hz,1H),6.35–6.15(m,1H),3.19(d,J=7.4Hz,2H),1.97(s,2H). 13 C NMR (100MHz, CDCl3): δ163.49,148.26,147.28,146.80,140.98,138.51,136.51,134.53,131.47,128.84,128. 60,128.55,128.02,127.54,127.08,126.46,121.79,121.77,120.87,116.83,60.79,45.81.HRMS(ESI):Calcd for C26 H 23 BrN3O[M+H] + Found: 472.1019; Found: 472.1017.

[0126] The structural formulas of the raw materials and products in Examples 1-15 and the corresponding experimental results are shown in Table 1 below:

[0127] Table 1

[0128]

[0129]

[0130]

[0131] Example 16

[0132] Example 16 uses the same method as Example 12, except that: the nickel is hydrated nickel bromide, the organic solvent is selected from methanol; the molar ratio of olefin, imine, nickel, and manganese is 1:1:0.1:3, the reaction temperature is 40°C, and the reaction time is 48 hours.

[0133] Example 17

[0134] Example 17 uses the same method as Example 12, except that: the nickel is nickel tetrafluoroborate hexahydrate; the organic solvent is selected from N,N-diacetamide; the molar ratio of olefin, imine, nickel, and manganese is 1:2:0.2:4; the reaction temperature is 60°C, and the reaction time is 24 hours. Comparative Example 1

[0135] The method of Comparative Example 1 is the same as that of Example 12, except that no nickel catalyst is added and the yield of the target product is 0.

[0136] Comparative Example 2

[0137] Comparative Example 2 uses the same method as Example 12, except that no manganese reducing agent is added and the yield of the target product is 0.

[0138] Comparative Example 3

[0139] Comparative Example 3 uses the same method as Example 12, except that the added olefin is... The structure (wherein the AQ structure is the same as in this invention) is such that the yield of the target product is 0.

[0140] Comparative Example 4

[0141] Comparative Example 4 uses the same method as Example 12, except that the added olefin is... The structure (wherein the AQ structure is the same as in this invention) is such that the yield of the target product is 0.

[0142] Comparative Examples 2 and 3 used internal olefins with stronger activity than terminal olefins, but their yields were significantly reduced. In particular, the olefin in Comparative Example 3 had a similar structure to the olefin used in the embodiments of the present invention, but the effect was significantly different, which further illustrates the importance of specific terminal olefins in the reaction system of the present invention.

[0143] Comparative Example 5

[0144] Comparative Example 5 uses the same method as Example 12, except that the reducing agent added is Zn, and the yield of the target product is 0.

[0145] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the invention. Theoretically, all nickel catalysts in this invention can react with olefins, thereby facilitating the smooth progress of the reaction. Manganese is a necessary reducing agent for oxidative cyclization reactions. The chemical bonds in the reaction of olefin substrates are the cyclization of carbon-carbon and carbon-nitrogen double bonds. The substituents at both ends of the carbon-nitrogen double bond affect the electron cloud density of the double bond and the steric hindrance during the reaction. That is, the modification of substituents only affects the reaction to a certain extent and does not play a decisive role in the occurrence of the reaction. Anyone skilled in the art will readily understand that, without departing from the scope of the present invention, variations or modifications can be made to obtain corresponding embodiments. For example, the substituents can be replaced, changed, or modified within the scope of the present invention to achieve the method of the present invention. Any modifications, alterations, or equivalent changes made to the above embodiments based on the present invention without departing from the spirit of the present invention are still within the scope of the present invention.

Claims

1. A method for synthesizing α-tertiary carbon homoallylic primary amines from non-activated olefins using nickel catalysis, characterized in that, The process includes the following steps: In an organic solvent, using manganese as a reducing agent and nickel as a catalyst, an imine undergoes oxidative cyclization coupling with an unactivated olefin to generate an α-tertiary carbon homoallylic primary amine. The general reaction formula is as follows: ； In the formula: Ar1 represents a substituted or unsubstituted phenyl, a substituted or unsubstituted biphenyl, a substituted or unsubstituted naphthyl, or a substituted or unsubstituted anthracene, wherein the substituents on the benzene ring are arbitrarily selected from hydrogen, C1 to C20 alkyl, C1 to C20 halosubstituted alkyl, C1 to C20 alkyl carbonyl, nitro, hydroxyl, cyano, silyl, amino or thio. Ar2 represents substituted or unsubstituted phenyl, substituted or unsubstituted biphenyl, substituted or unsubstituted naphthyl, or substituted or unsubstituted anthracene, wherein the substituents on the benzene ring are arbitrarily selected from hydrogen, C1-C20 alkyl, C1-C20 halosubstituted alkyl, C1-C20 alkyl carbonyl, nitro, hydroxyl, cyano, silyl, amino or thio. The nickel is nickel chloride, anhydrous nickel bromide, hydrated nickel bromide, or nickel tetrafluoroborate hexahydrate.

2. The method for synthesizing α-tertiary carbon homoallylic primary amines from nickel-catalyzed unactivated olefins according to claim 1, characterized in that, The organic solvent is selected from any one of methanol, ethanol, ethylene glycol, n-propanol, isopropanol, 1,3-propanediol, glycerol, n-butanol, isobutanol, tert-butanol, trifluoroethanol, 2-methyl-2-butanol, 3-methoxybutanol, sec-butanol, tert-amyl alcohol, 4-methyl-2-pentanol, isoamyl alcohol, 2-pentanol, 3-pentanol, cyclopentanol, n-pentanol, acetonitrile, benzonitrile, toluene, acetone, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dicarboxamide, N,N-diacetamide, N,N-dimethylpropenylurea, N-methylpyrrolidone, ethyl acetate, 1,4-dioxane, or tetrahydrofuran.

3. The method for synthesizing α-tertiary carbon homoallylic primary amines from nickel-catalyzed unactivated olefins according to claim 1, characterized in that, The organic solvent is selected from methanol, ethanol, N,N-diformamide, N,N-diacetamide, N,N-dimethylpropenylurea, or N-methylpyrrolidone.

4. The method for synthesizing α-tertiary carbon homoallylic primary amines from nickel-catalyzed unactivated olefins according to claim 1, characterized in that, The molar ratio of the olefin, imine, nickel, and manganese is 1:(1-2):(0.1-0.2):(3-4).

5. The method for synthesizing α-tertiary carbon homoallylic primary amines from nickel-catalyzed unactivated olefins according to claim 1, characterized in that, The reaction temperature is 40–60°C and the reaction time is 24–48 hours.

6. The method for synthesizing α-tertiary carbon homoallylic primary amines from nickel-catalyzed unactivated olefins according to claim 1, characterized in that, The reaction needs to be carried out in an inert gas atmosphere.

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