A method for the copper photocatalytic amination of unactivated halogenated hydrocarbons to prepare nitrogen alkylated compounds

Abstract

The application discloses a method for preparing a nitrogen alkylated compound by ammoxidation of an inactivated halogenated hydrocarbon through copper photocatalysis, which is characterized by using an LED lamp in a visible light wavelength range as a light source, generating a photoactive copper catalyst in-situ from a copper salt and a pyridine carbine ligand, catalyzing a cross-coupling reaction between an inactivated halogenated alkane and various nucleophilic reagents containing nitrogen atoms under the addition of a base, and preparing a nitrogen alkylated product. The method uses an inactivated halogenated hydrocarbon as a carbon radical precursor, does not need to use an additional photocatalyst and a halogen atom transfer reagent, can realize efficient preparation of the nitrogen alkylated product under mild conditions, can be used for modifying complex natural products and drug molecules, and is an economical and efficient synthesis method with wide application range and good operability, and is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical technology, and is a mild and efficient method for aminating halogenated hydrocarbons. The present application relates to a method for copper photocatalytic amination of unactivated halogenated hydrocarbons to prepare nitrogen-alkylated compounds. The present application is a method for photocatalytic pyridine carbene copper-catalyzed coupling of halogenated hydrocarbons and nitrogen nucleophilic substrates to prepare nitrogen-alkylated products and later functional group modified natural products and drug molecules. BACKGROUND

[0002] Nitrogen-containing compounds not only have significant biological activity, but also exist widely in many natural products and drug molecules. Generally, C(sp3)-N bond is the important structural basis of these compounds, and therefore how to construct C(sp3)-N bond has become a hotspot and difficulty in the academic and industrial fields (Vitaku, E., Smith, D. T. & Njardarson, J. T. J. Med. Chem. 57, 2014, 10257-10274).

[0003] Although the bimolecular substitution (S N 2) of N-nucleophiles with alkyl electrophiles such as halogenated alkanes is a classic reaction in organic chemistry, its practical application of halogenated hydrocarbons is limited to small steric hindrance primary (primary) or activated (benzyl, alpha-carbonyl) substrates (Fu, G. C., ACS Central Science, 2017, 3, 692-700). In recent years, copper photocatalysis has broadened the coupling reaction of unactivated halogenated hydrocarbons with a variety of N-nucleophiles using single electron transfer (SET) strategy (Hossain, A., Bhattacharyya, A. & Reiser, O. Science, 2019. 364, eaav9713). However, these methods are not universal, and multiple parameters such as ligand, light source, solvent, etc. need to be changed, and even different auxiliary ligands are needed to promote the reaction. In order to achieve the required reduction potential (E red <-2.0 V vs SCE) of unactivated halogenated hydrocarbons, the development of high-reducing copper catalytic system is crucial. Fu, Peter and their colleagues previously reported a high-reducing excited state copper (I)-amino complex (carbazole, indole, amide) for generating alkyl carbon radicals (Bissember, A. C., Lundgren, R. J., Creutz, S. E., Peters, J. C. & Fu, G. C., Angew. Chem. Int. Ed. 2013, 52, 5129-5133;

[0004] Do, H. Q., Bachman, S., Bissember, A. C., Peters, J. C. & Fu, G. C. J. Am. Chem. Soc. 2014, 136, 2162-2167;

[0005] Matier, C. D., Schwaben, J., Peters, J. C. & Fu, G. C. J. Am. Chem. Soc. 2017, 139, 17707-17710).

[0006] However, these methods can only be applied to specific types of nucleophiles. In subsequent studies, they found that a non-copper(I)-amino complex, a new P-N-P / P-P ligand- linked photo-redox copper catalyst enabled coupling. Although copper photocatalysis has made important progress, the low reduction potential of unactivated halogenated hydrocarbons remains the biggest obstacle to the development of their activation by SET strategy to couple with different N-nucleophilic substrates, so the application of N-nucleophilic substrates is still limited. On the other hand, the use of halogen atom transfer (XAT) strategy has successfully realized the generation of alkyl radicals from activated halogenated hydrocarbons, but in the process of using stoichiometric XAT reagents, a large amount of by-products is produced, which poses a challenge to sustainable synthesis.(Dow, N. W., Cabre, A. & MacMillan, D. A, Chem. 2021, 7, 1827-1842; Gó

[0007] rski, B., Barthelemy, A., Douglas, J. J., Julia, F. & Leonori, D. Nat. Catal. 2021, 4, 623-630). Other methods using carboxylic acids and their derivatives as alkyl radical precursors have been developed, but they cannot be extended to unactivated halogenated hydrocarbons at present. SUMMARY

[0008] The present application aims at the deficiencies existing in the prior art and provides a method for copper photocatalytic amination of unactivated halogenated hydrocarbons to prepare nitrogen alkylated compounds.

[0009] The method for copper photocatalytic amination of unactivated halogenated hydrocarbons of the present application uses an LED lamp in the visible light wavelength range as a light source, and the carbon-nitrogen bond cross-coupling of unactivated iodoalkanes and bromoalkanes with nitrogen nucleophiles to prepare nitrogen alkylated compounds. Under the catalysis of copper catalysts endogenously generated from copper salts and pyridine card ligands, the carbon-nitrogen bond cross-coupling of unactivated iodoalkanes and bromoalkanes with nitrogen nucleophiles to prepare nitrogen alkylated compounds. By adding a base, the carbon-nitrogen bond cross-coupling of unactivated iodoalkanes and bromoalkanes with nitrogen nucleophiles to prepare nitrogen alkylated compounds.

[0010] Specifically includes the following steps:

[0011] The carbon-nitrogen bond coupling is carried out under the conditions of nitrogen protection, addition of copper salt and pyridine carbene ligand, base, nitrogen nucleophile, unactivated halogenated hydrocarbon in acetonitrile, stirring under LED lamp irradiation for 5-50 hours to obtain the nitrogen alkylation product.

[0012]

[0013] The reaction temperature is 20-30°C, the molar ratio of copper salt to ligand is 1:1, the molar ratio of substrate nitrogen nucleophile, halogenated hydrocarbon to copper salt is 20:30:1, the concentration of base is 0.1M-0.2M, and the reaction time is 5-50 hours.

[0014] In the general formula, X is a halogen atom; R 1 is C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 aryl, C1-C10 alkylacyl, C1-C10 arylacyl, C1-C10 alkylsulfonyl, C1-C10 arylsulfonyl, C1-C10 arylaminocarbonyl, C1-C10 alkyl- oxycarbonyl, C1-C10 aryloxycarbonyl; R 2 is hydrogen atom, C1-C10 alkyl, C1-C10 aryl; R 1 and R 2 are connected or not connected, when connected, the general formula I is indole, carbazole, pyrrole, indazole; R 3 is C1-C10 alkyl, C1-C10 haloalkyl, C1-C10 heteroatom-containing alkyl.

[0015] The pyridine carbene ligand includes the following structural formula:

[0016]

[0017] "C1-C10 alkyl" represents straight-chain or branched-chain alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, cyclohexyl, etc., and alkyl containing double bond, triple bond, aryl, halogen atom, such as benzyl, allyl, propargyl, 2,2,2-trifluoroethyl, etc. "C1-C10 aryl" represents a substituent having aromatic ring structure property, such as phenyl, furanyl, thienyl, pyridyl, and aryl with different substituents on the aromatic ring, such as tolyl, p-trifluoromethylbenzene, p-methoxybenzene, etc. "Acyl" represents a substituent having acyl, such as p-methyl-substituted benzoyl, 3-pyridylbenzoyl, 2,2,2-trifluoroacetyl, etc. "Aminocarbonyl" represents a substituent having aminocarbonyl, such as phenylaminocarbonyl, etc. "Oxycarbonyl" represents a substituent having oxycarbonyl, such as tert-butyl-oxycarbonyl, etc. "Indole" represents a substituent connected with alkenyl or aryl, such as pyrrole, indole, etc.

[0018] The copper salt is monovalent copper and divalent copper and related complexes, including Cu(MeCN)4PF6, Cu(MeCN)4BF4, CuOAc, CuI, CuBr, CuCl, Cu(OAc)2, Cu(OTf)2, CuBr2, CuCl2.

[0019] The base is (1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), tetramethylguanidine (TMG), 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), lithium tert-butoxide or sodium tert-butoxide.

[0020] The solvent used is acetonitrile, ether solvents such as tetrahydrofuran, dimethyl sulfoxide, toluene or N,N-dimethylformamide.

[0021] The wavelength range of the LED lamp is 365-800 nm.

[0022] The present application is a new method that is efficient and economical, mild in conditions, widely applicable and can be used for industrial production. DETAILED DESCRIPTION

[0023] The following detailed description of the embodiments in conjunction with the technical documents is helpful for understanding the present application, but does not limit the present application.

[0024] According to R 1 and R 2 , various different nitrogen nucleophiles represented by general formula (1) are represented by 1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h, 1i, 1j, 1k, 1m, 1n, 1o, 1p, 1q, various different halogenated hydrocarbons represented by general formula (2) are represented by 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2m, 2n, 2o, 2p, 2q, and various different nitrogen alkylating compounds represented by general formula (3) are represented by 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, 2k, 2m, 2n, 2o, 2p, 2q, and so on.

[0025] In addition, it goes without saying that by the method of the present application, 3aa is generated by coupling of 1a and 2a, 3bb is generated by coupling of 1b and 2b, 3cc is generated by coupling of 1c and 2c, 3dd is generated by coupling of 1d and 2d, 3ee is generated by coupling of 1e and 2e, 3ff is generated by coupling of 1f and 2f, 3gg is generated by coupling of 1g and 2g, 3hh is generated by coupling of 1h and 2h, 3ii is generated by coupling of 1i and 2i, 3jj is generated by coupling of 1j and 2j, 3kk is generated by coupling of 1k and 2k, 3ll is generated by coupling of 1l and 2l, 3mm is generated by coupling of 1m and 2m, 3nn is generated by coupling of 1n and 2n, and so on.

[0026] Example 1:

[0027] 3aa(R 1 = 4-Me-C6H5, R 2 = H, )

[0028] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1 (0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and after being dissolved by stirring for ten minutes, the corresponding 1a (R 1 = C6H5, R 2 = H) (0.1 mmol), 2a (R X = I or Br) (0.2 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol) were added, and after being sealed, it was taken out and placed in a 410 nm LED lamp reactor, and stirred at 25 °C for 18 hours, with a yield of 93%.

[0029] 1 HNMR (400 MHz, CDCl3): δ 6.98 (d, J = 8.3 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 4.04 (br s, 2H), 3.44-3.34 (m, 1H), 2.91 (t, J = 12.7 Hz, 2H), 2.23 (s, 3H), 2.03 (d, J = 14.5 Hz, 2H), 1.46 (s, 9H), 1.36-1.28 (m, 2H). 13 CNMR (101 MHz, CDCl3): δ 154.8, 144.4, 129.8, 126.8, 113.6, 79.5, 50.4, 42.7, 32.4, 28.4, 20.3.

[0030] Example 2:

[0031] 3ba(R1 = 3,5-CF3-C6H5, R = H 2 = H, )

[0032] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and after complete dissolution by stirring for ten minutes, the corresponding 1a(R 1 = 3,5-CF3-C6H5, R = H 2 = H)(0.1 mmol), 2a( X = I)(0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed and taken out to be placed in a 410 nm LED lamp reactor, stirring at 25 °C for 18 hours, with a yield of 94%. 1 HNMR (400 MHz, CDC13): δ

[0033] 7.13 (s, 1H), 6.91 (s, 2H), 4.14-3.99 (m, 3H), 3.53-3.43 (m, 1H), 2.96 (t, J = 12.5 Hz, 2H), 2.05-1.99 (m, 2H), 1.47 (s, 9H), 1.42-1.32 (m, 2H). 13 CNMR (101 MHz, CDC13): δ

[0034] 154.7, 147.4, 132.5 (q, J = 32.7 Hz), 123.1 (q, J = 273.7), 112.0 (q, J = 10.1 Hz), 110.1 (q, J = 10.1 Hz), 79.9, 49.9, 42.6, 31.9, 28.4. 19 FNMR (377 MHz, CDC13): δ -63.2.

[0035] Example 3:

[0036] 3ca(R 1 = 2-OMe-4-F-C6H3, R = H 2 = H, )

[0037] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and after complete dissolution by stirring for ten minutes, the corresponding 1c(R 1= 2-OMe-4-F-C6H3, R = 3-CN-C6H3, R = H, 2 = H) (0.1 mmol), 2a (0.1 mmol), 1 mL anhydrous acetonitrile, 25 °C, 18 h, 99% yield. X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), remove the septum, put it in a 410 nm LED lamp reactor, 25 °C, stirring for 18 h, 94% yield. 1 HNMR (400 MHz, CDC13): δ

[0038] 7.13 (s, 1H), 6.91 (s, 2H), 4.14-3.99 (m, 3H), 3.53-3.43 (m, 1H), 2.96 (t, J = 12.5 Hz, 2H), 2.05-1.99 (m, 2H), 1.47 (s, 9H), 1.42-1.32 (m, 2H). 13 CNMR (101 MHz, CDC13): δ

[0039] 154.7, 147.4, 132.5 (q, J = 32.7 Hz), 123.1 (q, J = 273.7), 112.0 (q, J = 10.1 Hz), 110.1 (q, J = 10.1 Hz), 79.9, 49.9, 42.6, 31.9, 28.4. 19 FNMR (377 MHz, CDC13): δ -63.2.

[0040] Example 4:

[0041] 3da (R 1 = 2-OMe-4-F-C6H3, R = 3-CN-C6H3, R = H, 2 = H, )

[0042] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1 (0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL anhydrous acetonitrile was added, stirred for ten minutes to dissolve, then the corresponding 1d (R 1 = 2-OMe-4-F-C6H3, R = 3-CN-C6H3, R = H, 2 = H) (0.1 mmol), 2a (0.1 mmol), 1 mL anhydrous acetonitrile, 25 °C, 18 h, 99% yield. X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), remove the septum, put it in a 410 nm LED lamp reactor, 25 °C, stirring for 18 h, 94% yield. 1 HNMR (400 MHz, CDC13): δ

[0043] 7.21(t,J=7.9Hz,1H),6.94(d,J=7.5Hz,1H),6.81-6.74(m,2H),4.16-3.98(m,2H),3.85-3.75(m,1H ),3.46-3.35(m,1H),2.93(t,J=12.5Hz,2H),2.02(d,J=12.5Hz,2H),1.47(s,9H),1.38-1.31(m,2H). 13 CNMR (101MHz, CDCl3): δ 154.7,147.0,130.0,120.8,119.4,117.6,115.2,113.1,79.8,49.9,42.5,32.0,28.4.

[0044] Example 5:

[0045] 3ea(R 1 =3-C5H3N,R 2 =H, )

[0046] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding amount of 1e (R). 1 =3-C5H3N,R 2 =H)(0.1mmol), 2a( X = I or Br)(0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed and placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, yield 62%. 1HNMR (400MHz, CDCl3): δ8.04-7.92(m,2H),7.07(dd,J=8.3,4.6Hz,1H),6.89-6.84(m,1H),4.11-3.99(m,2H),3.61 (d,J=7.0Hz,1H),3.48-3.36(m,1H),2.92(t,J=12.1Hz,2H),2.03(d,J=14.6Hz,2H),1.46(s,9H),1.40-1.28(m,2H). 13 CNMR (101MHz, CDCl3): δ154.7,142.8,138.8,136.3,123.8,119.1,79.7,49.9,42.6,32.1,28.4.

[0047] Example 6:

[0048] 3fa(R 1 =2-C5H3N,R 2 =H, )

[0049] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding 1f(R) 1 =2-C5H3N,R 2 =H)(0.1mmol), 2a( X = I or Br)(0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed and placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, yield 62%. 1 HNMR (400MHz, CDCl3): δ

[0050] 8.05(d,J=4.3Hz,1H),7.41-7.34(m,1H),6.58-6.52(m,1H),6.35(d,J=8.4Hz,1H),4.39(d,J=8.0Hz,1H),4.1 1-3.95(m,2H),3.85-3.71(m,1H),2.94(t,J=12.5Hz,2H),2.05-2.00(m,2H),1.45(s,9H),1.40-1.29(m,2H). 13 CNMR (101MHz, CDCl3): δ 157.6,154.7,148.1,137.4,112.8,107.4,79.5,48.3,42.5,32.3,28.4.

[0051] Example 7:

[0052] 3fa(R 1 =2,4-C5H3N,R 2 =H, )

[0053] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding 1f(R) 1= 2,4-C5H3N, R 2 = H), 2a (0.1 mmol), 1f (R X = I or Br) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), remove the Schlenk tube from the glove box, place it in a 410 nm LED lamp reactor, stir at 25 °C for 18 h, yield 98%. 1 HNMR (400 MHz, CDC13): δ

[0054] 7.96 (s, 1H), 7.86 (s, 1H), 7.78 (d, J = 2.3 Hz, 1H), 4.54-4.48 (m, 1H), 4.15-4.00 (m, 2H), 3.96-3.83 (m, 1H), 2.93 (t, J = 11.9 Hz, 2H), 2.04 (d, J = 12.1 Hz, 2H), 1.46 (s, 9H), 1.42-1.31 (m, 2H). 13 CNMR (101 MHz, CDC13): δ 154.7, 153.7, 141.9, 132.8, 132.6, 79.7, 48.0, 42.4, 32.1, 28.4.

[0055] Example 8:

[0056] 3fa (R 1 = 2,5-C4H3N2, R 2 = H, )

[0057] In a glove box nitrogen atmosphere, CuOAc (0.005 mmol), L1 (0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL anhydrous acetonitrile was added, stirred well for ten minutes to dissolve, then the corresponding 1f (R 1 = R 1 = 2,5-C4H3N2, R 2 = H), 2a (0.1 mmol), 1f (R X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), remove the Schlenk tube from the glove box, place it in a 410 nm LED lamp reactor, stir at 25 °C for 18 h, yield 98%. 1 HNMR (400 MHz, CDC13): δ

[0058] 8.25 (d, J = 4.8 Hz, 2H), 6.52 (t, J = 4.8 Hz, 1H), 5.22 (d, J = 7.4 Hz, 1H), 4.16-3.84 (m, 3H), 2.93 (t, J = 11.8 Hz, 2H), 2.11-1.98 (m, 2H), 1.45 (s, 9H), 1.41-1.33 (m, 2H). 13 CNMR (101 MHz, CDC13): δ 161.6, 158.0, 154.7, 110.7, 79.6, 48.1, 42.6, 32.1, 28.4.

[0059] Example 9:

[0060] 3ga(R 1 = 4-Cl-5-C5H3N, R 2 = H, )

[0061] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, stirred thoroughly for ten minutes to dissolve, then the corresponding 1 g(R 1 = 4-Cl-5-C5H3N, R 2 = H, R 3 = C 10 H 19 NO2, R 2 = H) (0.1 mmol), 2a X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed, removed, placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, yield 48%. 1 HNMR (400 MHz, CDC13): δ

[0062] 7.75 (d, J = 3.1 Hz, 1H), 7.08 (d, J = 8.6 Hz, 1H), 6.86 (dd, J = 8.6, 3.1 Hz, 1H), 4.12-3.99 (m, 2H), 3.62 (d, J = 7.8 Hz, 1H), 3.45-3.31 (m, 1H), 2.91 (t, J = 12.6 Hz, 2H), 2.09-1.98 (m, 2H), 1.46 (s, 9H), 1.38-1.29 (m, 2H). 13CNMR (101 MHz, CDC13): δ 154.7, 141.9, 139.0, 134.9, 124.1, 122.5, 79.8, 50.1, 42.4, 32.0, 28.4.

[0063] Example 10:

[0064] 3ha(R 1 and R 3 = C 10 H 19 NO2)

[0065] CuOAc (0.005 mmol), L1 (0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar under a nitrogen atmosphere, 1 mL of anhydrous acetonitrile was added, and the mixture was stirred for ten minutes to dissolve. The corresponding 1h (0.1 mmol), 2a (R 3 = C 10 H 19 NO2, X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol) were added, the tube was sealed, removed from the glovebox, and placed in a 410 nm LED lamp reactor. The mixture was stirred at 25 °C for 18 h to give a 62% yield. 1 HNMR (400 MHz, CDC13): δ

[0066] 7.68 (d, J = 8.2 Hz, 1H), 7.45-7.41 (m, 2H), 7.23-7.18 (m, 1H), 4.58-4.45 (m, 1H), 4.31 (br s, 2H), 2.93 (br s, 2H), 2.30-2.15 (m, 2H), 1.99 (d, J = 11.9 Hz, 2H), 1.48 (s, 9H). 13 CNMR (101 MHz, CDC13): δ 154.5, 140.0, 132.8, 127.3, 121.3, 121.1, 120.0, 109.1, 79.8, 56.5, 42.7, 31.4, 28.4.

[0067] Example 11:

[0068] 3ia(R 1 and )

[0069] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, and after being dissolved by stirring for ten minutes, the corresponding 1i (0.1 mmol), 2a X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after being sealed, it was taken out and placed in a 410 nm LED lamp reactor, and stirred at 25 °C for 18 hours, with a yield of 40%. 1H NMR (400 MHz, CDC13): δ 7.65 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.24-7.20 (m, 1H), 7.19 (d, J = 3.3 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.54 (d, J = 3.1 Hz, 1H), 4.43-4.25 (m, 3H), 2.91 (t, J = 13.8 Hz, 2H), 2.09 (d, J = 12.6 Hz, 2H), 1.98-1.85 (m, 2H), 1.51 (s, 9H). 13 CNMR (101 MHz, CDC13): δ 154.7, 135.4, 128.5, 123.8, 121.4, 121.1, 119.5, 109.1, 101.7, 79.9, 53.4, 43.5, 32.3, 28.4.

[0070] Example 12:

[0071] 3ja(R 1 and )

[0072] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, and after being dissolved by stirring for ten minutes, the corresponding 1j (0.1 mmol), 2a X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after being sealed, it was taken out and placed in a 410 nm LED lamp reactor, and stirred at 25 °C for 18 hours, with a yield of 40%. 1H NMR (400 MHz, CDC13): δ 7.65 (d, J = 7.8 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.24-7.20 (m, 1H), 7.19 (d, J = 3.3 Hz, 1H), 7.12 (t, J = 7.8 Hz, 1H), 6.54 (d, J = 3.1 Hz, 1H), 4.43-4.25 (m, 3H), 2.91 (t, J = 13.8 Hz, 2H), 2.09 (d, J = 12.6 Hz, 2H), 1.98-1.85 (m, 2H), 1.51 (s, 9H). 1 HNMR (400 MHz, CDC13): δ

[0073] 8.16(d,J=7.7Hz,2H),7.56(d,J=8.3Hz,2H),7.49(t,J=7.2Hz,2H),7.32-7.24(m,2H),4.75-4.62(m ,1H),4.45(brs,2H),3.00(t,J=11.6Hz,2H),2.73-2.56(m,2H),1.96(d,J=12.5Hz,2H),1.59(s,9H).

[0074] 13 CNMR (101MHz, CDCl3): δ 154.8,139.4,125.5,123.4,120.4,118.9,109.9,80.0,53.5,43.9,29.6,28.4.

[0075] Example 13:

[0076] 3ka(R 1 =4-Me-C6H4CO,R 2 =H, )

[0077] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding 1 kJ / L1 solution. 1 =4-Me-C6H4CO,R 2 =H)(0.1mmol), 2a( X = I or Br (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after sealing, were placed in a 410 nm LED lamp reactor and stirred at 25 °C for 18 hours, with a yield of 93%. 1 HNMR (400MHz, CDCl3): δ

[0078] 7.64(d,J=8.2Hz,2H),7.21(d,J=8.1Hz,2H),6.10(d,J=8.0Hz,1H),4.10(dt,J=15.2,4 .8Hz,3H),2.88(t,J=12.7Hz,2H),2.38(s,3H),2.10-1.95(m,2H),1.50-1.33(m,11H). 13CNMR (101MHz, CDCl3): δ 166.8,154.7,141.9,131.6,129.2,126.8,79.6,47.1,42.8,32.1,28.4,21.4.

[0079] Example 14:

[0080] 3la(R 1 and )

[0081] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding 1 L (R 1 and R 2 =H)(0.1mmol), 2a( X=I)(0.15mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD))(0.18mmol, were sealed and placed in a 410nm LED lamp reactor and stirred at 25°C for 18 hours, with a yield of 85%. 1 HNMR (400MHz, CDCl3): δ

[0082] 7.64(d,J=8.2Hz,2H),7.21(d,J=8.1Hz,2H),6.10(d,J=8.0Hz,1H),4.10(dt,J=15.2,4 .8Hz,3H),2.88(t,J=12.7Hz,2H),2.38(s,3H),2.10-1.95(m,2H),1.50-1.33(m,11H). 13 CNMR (101MHz, CDCl3): δ

[0083] 166.8,154.7,141.9,131.6,129.2,126.8,79.6,47.1,42.8,32.1,28.4,21.4. 1 HNMR (400MHz, CDCl3): δ

[0084] 4.28-3.99 (m, 3H), 3.31 (t, J = 7.0 Hz, 2H), 2.86-2.68 (m, 2H), 2.38 (t, J = 8.1 Hz, 2H), 2.07-1.93 (m, 2H), 1.84 (br s, 1H), 1.67-1.59 (m, 1H), 1.58-1.50 (m, 2H), 1.44 (s, 9H). 13 CNMR (101 MHz, CDC13): δ 174.5, 154.6, 79.7, 48.8, 43.0, 42.8, 31.4, 29.1, 28.4, 18.1.

[0085] Example 15:

[0086] 3ma( R 2 = H, )

[0087] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, stirred thoroughly for ten minutes to dissolve, then the corresponding 1m (R 1 and ) (0.1 mmol), 2a X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol) were added, sealed, removed from the glove box, placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, 85% yield. 1 HNMR (400 MHz, CDC13): δ

[0088] 7.64 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.1 Hz, 2H), 6.10 (d, J = 8.0 Hz, 1H), 4.10 (dt, J = 15.2, 4.8 Hz, 3H), 2.88 (t, J = 12.7 Hz, 2H), 2.38 (s, 3H), 2.10-1.95 (m, 2H), 1.50-1.33 (m, 11H). 13 CNMR (101 MHz, CDC13): δ

[0089] 166.8, 154.7, 141.9, 131.6, 129.2, 126.8, 79.6, 47.1, 42.8, 32.1, 28.4, 21.4. 1 HNMR (400 MHz, CDC13): δ

[0090] 4.28-3.99(m,3H),3.31(t,J=7.0Hz,2H),2.86-2.68(m,2H),2.38(t,J=8.1Hz,2H),2 .07-1.93(m,2H),1.84(brs,1H),1.67-1.59(m,1H),1.58-1.50(m,2H),1.44(s,9H). 13 CNMR (101MHz, CDCl3): δ 174.5,154.6,79.7,48.8,43.0,42.8,31.4,29.1,28.4,18.1.

[0091] Example 16:

[0092] 3na(R 1 =CH2CH2C6H5, R 2 =H, )

[0093] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding amount of 1n(R) 1 =CH2CH2C6H5, R 2 =H)(0.1mmol), 2a( X=I)(0.15mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD))(0.18mmol, were sealed and placed in a 410nm LED lamp reactor and stirred at 25°C for 18 hours, with a yield of 93%. 1 HNMR (400MHz, CDCl3): δ

[0094] 7.32-7.27(m,2H),7.23-7.17(m,3H),4.12-3.91(m,2H),2.90(t,J=7.0Hz,2H),2.83-2 .70(m,4H),2.65-2.55(m,2H),1.80(d,J=12.9Hz,2H),1.43(s,9H),1.28-1.19(m,2H). 13 CNMR (101MHz, CDCl3): δ 154.8,139.8,128.6,128.5,126.2,79.4,54.9,47.9,42.5,36.4,32.4,28.4.

[0095] Example 17:

[0096] 3ab(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2b 2 = H, )

[0097] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and after complete dissolution by stirring for ten minutes, the corresponding 1a(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2b X = I) (0.2 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), and after sealing, it was removed and placed in a 410 nm LED lamp reactor, stirring at 25 °C for 18 hours, with a 93% yield.

[0098] 1 HNMR (400 MHz, CDC13): δ 7.00 (d, J = 8.0 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.46-3.27 (m, 2H), 2.24 (s, 3H), 2.18-2.05 (m, 4H), 1.97-1.78 (m, 2H), 1.62-1.47 (m, 2H).13C NMR (101 MHz, CDC13): δ 144.5, 129.9, 127.0, 122.9 (t, J = 242.4 Hz), 113.6, 49.9, 32.0 (t, J = 24.7 Hz), 28.8 (d, J = 8.0 Hz), 20.3. 19 FNMR (377 MHz, CDC13): δ -95.5 (d, J = 236.6 Hz), -99.9 (d, J = 236.2 Hz).

[0099] Example 18:

[0100] 3ac(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2b 2 = H, )

[0101] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and after complete dissolution by stirring for ten minutes, the corresponding 1a(R 1= 4-Me-C6H5, R = H) (0.1 mmol), 2c X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after sealing, remove and place in a 410 nm LED lamp reactor, stirring at 25 °C for 18 hours, yield 84%. 1 HNMR (400 MHz, CDC13, diastereomers): δ

[0102] 6.99 (d, J = 8.0 Hz, 2H), 6.52-6.46 (m, 2H), 4.21-4.07 (m, 0.68H), 3.96-3.83 (m, 0.43H), 3.73 (s, 1.87H), 3.69 (s, 1.09H), 3.21-3.09 (m, 0.77H), 2.94-2.82 (m, 0.60H), 2.77-2.66 (m, 2.15H), 2.24 (s, 3.07H), 2.19-2.05 (m, 2.14H). 13 CNMR (101 MHz, CDC13, diastereomers): δ 176.3, 175.3, 144.5, 144.3, 129.8, 127.1, 113.3, 113.3, 51.9, 51.8, 47.0, 45.2, 34.7, 33.5, 33.0, 31.4, 20.3.

[0103] Example 19:

[0104] 3ad(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2c 2 = H, )

[0105] In a glove box nitrogen atmosphere, CuOAc (0.005 mmol), L1 (0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, after stirring for ten minutes to dissolve, the corresponding 1a (R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2d X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after sealing, remove and place in a 410 nm LED lamp reactor, stirring at 25 °C for 18 hours, yield 71%.

[0106] 1HNMR (400 MHz, CDC13): δ 7.00 (d, J = 8.0 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.46-3.27 (m, 2H), 2.24 (s, 3H), 2.18-2.05 (m, 4H), 1.97-1.78 (m, 2H), 1.62-1.47 (m, 2H).13C NMR (101 MHz, CDC13): δ 144.5, 129.9, 127.0, 122.9 (t, J = 242.4 Hz), 113.6, 49.9, 32.0 (t, J = 24.7 Hz), 28.8 (d, J = 8.0 Hz), 20.3. 19 FNMR (377 MHz, CDC13): δ -95.5 (d, J = 236.6 Hz), -99.9 (d, J = 236.2 Hz).

[0107] Example 20:

[0108] 3ae(R 1 = 4-Me-C6H5, R 2 = H, )

[0109] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, stirred thoroughly for ten minutes to dissolve, then the corresponding 1a(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2e X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed, removed, placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, yield 42%. 1 HNMR (400 MHz, CDC13): δ

[0110] 7.71 (d, J = 8.2 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.1 Hz, 2H), 6.34 (d, J = 8.3 Hz, 2H), 3.95-3.89 (m, 1H), 3.53-3.47 (m, 1H), 3.40-3.24 (m, 3H), 3.21-3.14 (m, 1H), 2.45 (s, 3H), 2.23 (s, 3H), 2.16-2.04 (m, 1H), 1.88-1.75 (m, 1H). 13CNMR (101 MHz, CDC13): δ 143.8, 143.6, 133.1, 129.7, 129.7, 127.6, 127.3, 113.4, 53.8, 52.8, 46.1, 31.5, 21.5, 20.3.

[0111] Example 21:

[0112] 3af(R 1 = 4-Me-C6H5, R 2 = H, )

[0113] CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar under a nitrogen atmosphere, 1 mL of anhydrous acetonitrile was added, stirred thoroughly for ten minutes to dissolve, then the corresponding 1a(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2f X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol) were added, sealed, removed from the glove box, and placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 h, 62% yield. 1 HNMR (400 MHz, CDC13): δ

[0114] 6.98 (d, J = 8.0 Hz, 2H), 6.46 (d, J = 8.2 Hz, 2H), 3.94-3.84 (m, 1H), 3.64 (br s, 1H), 3.42-3.35 (m, 2H), 3.34-3.25 (m, 3H), 2.41-2.32 (m, 2H), 2.23 (s, 3H), δ

[0115] 1.64-1.58 (m, 3H), 1.55-1.50 (m, 3H), 1.45 (s, 9H). 13 CNMR (101 MHz, CDC13): δ 144.9, 129.7, 126.8, 113.2, 79.3, 43.9, 40.7, 40.5, 36.6, 32.5, 28.4, 20.4.

[0116] Example 22:

[0117] 3ag(R 1 = 4-Me-C6H5, R 2 = H, )

[0118] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and the mixture was stirred for 10 min to dissolve. The corresponding 1a(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2g X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), and the mixture was stirred at 25 °C for 18 h. The yield was 75%. 1 HNMR (400 MHz, CDC13): δ

[0119] 6.97 (d, J = 8.1 Hz, 2H), 6.50 (d, J = 8.4 Hz, 2H), 3.33-3.21 (m, 2H), 2.23 (s, 3H), 1.64-1.54 (m, 2H), 1.51-1.43 (m, 2H), 1.38-1.29 (m, 4H), 0.95-0.88 (m, 6H). 13 CNMR (101 MHz, CDC13): δ 146.0, 129.7, 125.6, 113.1, 54.3, 34.1, 28.2, 27.2, 22.8, 20.3, 14.1, 10.0.

[0120] Example 23:

[0121] 3ah(R 1 = 4-Me-C6H5, R 2 = H, )

[0122] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and the mixture was stirred for 10 min to dissolve. The corresponding 1a(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2h X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), and the mixture was stirred at 25 °C for 18 h. The yield was 75%. 1 HNMR (400 MHz, CDC13): δ

[0123] 7.02(d,J=8.1Hz,2H),6.55(d,J=8.4Hz,2H),4.44(d,J=5.1Hz,1H),3.45(brs,1H),3.26(s,1H),3.20(t,J=4.4Hz,1H),2 .61(dd,J=11.2,4.5Hz,1H),2.44(s,1H),2.25(s,3H),2.15-2.05(m,2H),1.84(d,J=13.4Hz,1H),1.67(d,J=10.6Hz,1H). 13 CNMR (101MHz, CDCl3): δ 180.3,143.3,130.0,127.6,113.3,84.7,62.3,45.6,42.3,38.6,35.0,33.6,20.3.

[0124] Example 24:

[0125] 3ai(R 1 =4-Me-C6H5,R 2 =H, )

[0126] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding amount of 1a (R 1 =4-Me-C6H5, R=H) (0.1mmol), 2i( X=I)(0.15mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD))(0.18mmol, were sealed and placed in a 410nm LED lamp reactor and stirred at 25°C for 18 hours, yield 66%. 1 HNMR (400MHz, CDCl3): δ

[0127] 6.96(d,J=8.1Hz,2H),6.50(d,J=8.1Hz,2H),4.73(s,1H),3.17-3.06(m,1H),2.25-2.12(m,5H),1 .77-1.68(m,2H),1.48-1.38(m,1H),1.16-1.06(m,2H),0.94-0.85(m,8H),0.76(d,J=6.9Hz,3H).

[0128] 13CNMR (101MHz, CDCl3): δ 145.8,129.8,125.6,113.0,53.8,48.8,42.9,34.9,32.0,26.3,24.2,22.2,21.2,20.3,16.2.

[0129] Example 25:

[0130] 3aj(R 1 =4-CH2CH2OH-C6H5,R 2 =H, )

[0131] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding 10 mL of acetonitrile. 1 =4-Me-C6H5, R=H) (0.1mmol), 2i( X=I)(0.15mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD))(0.18mmol, were sealed and placed in a 410nm LED lamp reactor and stirred at 25°C for 18 hours, yield 56%. 1 HNMR (400MHz, CDCl3): δ

[0132] 7.02(d,J=8.2Hz,2H),6.54(d,J=8.3Hz,2H),3.79(t,J=6.5Hz,2H),3.47(brs,1 H),3.31-3.20(m,1H),2.83-2.67(m,6H),2.39-2.29(m,2H),1.64-1.50(m,2H). 13 CNMR (101MHz, CDCl3): δ145.2,129.9,127.0,113.6,63.9,51.2,38.2,34.5,27.8.

[0133] Example 26:

[0134] 3ok(R 1 =4-CH2CH2OH-C6H5,R 2 =H, )

[0135] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, and after being dissolved by stirring for ten minutes, the corresponding 1o(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2k X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after being sealed, it was taken out and placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, with a yield of 75%. 1 HNMR (400 MHz, CDC13): δ

[0136] 7.03 (d, J = 8.4 Hz, 2H), 6.58 (d, J = 8.4 Hz, 2H), 4.06-3.95 (m, 2H), 3.79 (t, J = 6.5 Hz, 2H), 3.56-3.39 (m, 3H), 2.75 (t, J = 6.6 Hz, 2H), 2.03 (d, J = 13.5 Hz, 2H), 1.54-1.37 (m, 2H). 13 CNMR (101 MHz, CDC13): δ 145.3, 129.9, 127.1, 113.7, 66.8, 63.9, 49.2, 38.2, 33.6.

[0137] Example 27:

[0138] 3ol (R 1 = 4-CH2CH2OH-C6H5, R 2 = H, )

[0139] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, and after being dissolved by stirring for ten minutes, the corresponding 1o(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2l X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), after being sealed, it was taken out and placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, with a yield of 75%. 1 HNMR (400 MHz, CDC13): δ

[0140] 7.02 (d, J = 8.2 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 4.81 - 4.66 (m, 1H), 4.01 (dd, J = 11.3, 3.9 Hz, 2H), 3.79 (t, J = 6.5 Hz, 2H), 3.44 - 3.24 (m, 3H), 2.75 (t, J = 6.5 Hz, 2H), 1.78 - 1.71 (m, 1H), 1.69 - 1.59 (m, 2H), 1.51 - 1.39 (m, 2H), 1.14 (d, J = 6.4 Hz, 3H). 13 CNMR (101 MHz, CDC13): δ 146.3, 129.9, 126.4, 113.3, 68.2, 68.0, 63.9, 52.8, 40.6, 38.2, 29.8, 28.7, 17.5.

[0141] Example 28:

[0142] 3om(R 1 = 4-CH2CH2OH-C6H5, R 2 = H, )

[0143] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL of anhydrous acetonitrile was added, stirred thoroughly for ten minutes to dissolve, then the corresponding 1o(R 1 = 4-Me-C6H5, R = H) (0.1 mmol), 2m X = Br) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed, removed, placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, 40% yield. 1 HNMR (400 MHz, CD2CI2): δ

[0144] 7.01 (d, J = 8.3 Hz, 2H), 6.71 (d, J = 8.4 Hz, 2H), 4.16 (br s, 1H), 3.72 (t, J = 6.6 Hz, 2H), 2.70 (t, J = 6.6 Hz, 2H), 2.38 (tt, J = 6.8, 3.6 Hz, 1H), 0.69 (td, J = 6.6, 4.6 Hz, 2H), 0.47 - 0.43 (m, 2H). 13CNMR (101 MHz, CD2CI2): δ 147.0, 129.1, 127.0, 112.7, 63.4, 37.9, 24.8, 6.7.

[0145] Example 29:

[0146] 3pn(R 1 = 4-CH2CH2OH-C6H5, R 2 = H, )

[0147] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, stirred thoroughly for ten minutes to dissolve, then the corresponding 1p(R 1 = 4-F-C6H5, R = H) (0.1 mmol), 2n X = Br) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), sealed, removed from the glove box, placed in a 410 nm LED lamp reactor, stirred at 25 °C for 18 hours, 40% yield. 1 HNMR (400 MHz, CDC13): δ

[0148] 6.91-6.82 (m, 2H), 6.51-6.43 (m, 2H), 3.50-3.32 (m, 2H), 2.05-1.93 (m, 2H), 1.73-1.60 (m, 4H), 1.54-1.39 (m, 6H). 13 CNMR (101 MHz, CDC13): δ

[0149] 155.6 (d, J = 234.6 Hz), 143.5, 115.6 (d, J = 22.4 Hz), 114.2 (d, J = 7.2 Hz), 54.5, 34.7, 28.3, 24.4. 19 FNMR (377 MHz, CDC13): δ -128.6.

[0150] Example 30:

[0151] 3qa( R 2 = H, )

[0152] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and the mixture was stirred for 10 min to dissolve. Then, the corresponding 1q R = H)(0.1 mmol), 2a X = I)(0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol) were added. The reaction mixture was removed from the glove box, placed in a 410 nm LED lamp reactor, and stirred at 25 °C for 18 h. The yield was 64%. 1 HNMR (400 MHz, CDC13): δ 7.18 (d, J = 8.2 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.89 (s, 1H), 3.95 (br s, 2H), 2.94-2.77 (m, 5H), 2.62-2.45 (m, 2H), 2.26 (d, J = 12.0 Hz, 2H), 1.85-1.70 (m, 6H), 1.64-1.60 (m, 1H), 1.45 (s, 9H), 1.44-1.34 (m, 5H), 1.25-1.21 (m, 9H), 0.90 (s, 3H). 13 CNMR (101 MHz, CDC13): δ 154.8, 147.6, 145.4, 134.8, 126.8, 124.3, 123.8, 79.2, 58.2, 55.3, 44.9, 42.6, 38.4, 37.4, 36.8, 36.0, 33.4, 32.6, 30.3, 28.4, 25.4, 23.9, 19.4, 18.8, 18.7.

[0153]

[0154] Example 31:

[0155] 3ra R 2 = H, )

[0156] In a glove box under nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube equipped with a stir bar, 1 mL of anhydrous acetonitrile was added, and the mixture was stirred for 10 min to dissolve. Then, the corresponding 1r R = H)(0.1 mmol), 2a X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), remove the Schlenk tube from the glove box, place it in a 410 nm LED lamp reactor, stir at 25 °C for 18 h, yield 81 %. 1 HNMR (400 MHz, CDC13): δ 7.85 (d, J = 8.4 Hz, 2H), 7.70 (s, 1H), 7.49 (dd, 1H), 7.31-7.24 (m, 1H), 5.65 (d, J = 7.6 Hz, 1H), 4.53-4.40 (m, 1H), 4.24 (d, J = 7.4 Hz, 1H), 4.10 (br s, 1H), 3.02 (t, J = 10.5 Hz, 2H), 2.33 (dt, J = 13.6, 6.5 Hz, 1H), 2.19 (d, J = 9.9 Hz, 2H), 1.56-1.50 (m, 2H), 1.47 (s, 9H), 1.00 (d, J = 6.6 Hz, 6H). 13 CNMR (101 MHz, CDC13): δ 154.9, 149.9, 145.4, 141.8, 131.9, 128.7, 127.6, 127.2, 121.7, 119.8, 115.1, 79.4, 55.0, 47.1, 42.9, 32.4, 28.7, 28.4, 19.7.

[0157] Example 32:

[0158] 3sa(R 1 and )

[0159] In a glove box nitrogen atmosphere, CuOAc (0.005 mmol), L1(0.005 mmol) were weighed into a 10 mL Schlenk tube with a stir bar, 1 mL anhydrous acetonitrile was added, stirred for ten minutes to dissolve, then the corresponding 1s (0.1 mmol), 2a X = I) (0.15 mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) (0.18 mmol), remove the Schlenk tube from the glove box, place it in a 410 nm LED lamp reactor, stir at 25 °C for 18 h, yield 81 %. 1 HNMR (400 MHz, CDC13): δ 7.85 (d, J = 8.4 Hz, 2H), 7.70 (s, 1H), 7.49 (dd, 1H), 7.31-7.24 (m, 1H), 5.65 (d, J = 7.6 Hz, 1H), 4.53-4.40 (m, 1H), 4.24 (d, J = 7.4 Hz, 1H), 4.10 (br s, 1H), 3.02 (t, J = 10.5 Hz, 2H), 2.33 (dt, J = 13.6, 6.5 Hz, 1H), 2.19 (d, J = 9.9 Hz, 2H), 1.56-1.50 (m, 2H), 1.47 (s, 9H), 1.00 (d, J = 6.6 Hz, 6H).

[0160] 6.63(s,1H),6.50(s,2H),4.84-4.76(m,1H),4.27-4.16(m,2H),4.11-4.01(m,2H),3.94-3.82(m,1H),3.63(t,J=8.7Hz, 1H),3.48(dd,J=8.6,5.6Hz,1H),2.84-2.70(m,2H),2.27(s,6H),1.77(d,J=9.7Hz,2H),1.62-1.52(m,2H),1.45(s,9H). 13 CNMR (101MHz, CDCl3): δ 158.1,156.8,154.5,139.4,123.3,112.2,79.8,71.0,67.9,50.9,42.7,29.2,29.0,28.3,21.3.

[0161] Example 33:

[0162] 3ao(R 1 =4-Me-C6H5, )

[0163] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding amount of 1a (R 1 =4-Me-C6H5,R 2 =H)(0.1mmol), 2a( X=I)(0.15mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD))(0.18mmol, were sealed and placed in a 410nm LED lamp reactor and stirred at 25°C for 18 hours, with a yield of 85%. 1 HNMR (400MHz, CDCl3): δ

[0164] 6.97(d,J=8.0Hz,2H),6.59(d,J=8.2Hz,2H),5.55(d,J=5.0Hz,1H),4.61(dd,J=7.9,2.4Hz,1H),4.32(dd,J=5.1,2.4Hz,1H),4.24(dd,J =7.9,1.9Hz,1H),4.04-3.98(m,1H),3.86(brs,1H),3.43-3.23(m,2H),2.22(s,3H),1.47(s,3H),1.38(s,3H),1.36(s,3H),1.31(s,3H). 13 CNMR (101MHz, CDCl3): δ 145.8,129.7,126.9,113.6,109.4,108.7,96.4,71.8,70.8,70.6,65.7,44.5,26.0,25.8,25.0,24.4,20.3.

[0165] Example 34:

[0166] 3ap(R 1 =4-Me-C6H5, )

[0167] In a glove box under a nitrogen atmosphere, weigh 0.005 mmol of CuOAc and 0.005 mmol of L1 into a 10 mL Schlenk tube equipped with a stir bar. Add 1 mL of anhydrous acetonitrile and stir thoroughly for ten minutes to dissolve. Then add the corresponding amount of 1a (R 1 =4-Me-C6H5,R 2 =H)(0.1mmol), 2a( X=I)(0.15mmol), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD))(0.18mmol, were sealed and placed in a 410nm LED lamp reactor and stirred at 25°C for 18 hours, yield 84%.

[0168] 1 HNMR (400MHz, CDCl3, diastereomers): δ

[0169] 6.97 (d, J = 8.1 Hz, 2H), 6.52 (d, J = 8.2 Hz, 2H), 5.39-5.35 (m, 1H), 3.23-3.11 (m, 0.90H), 2.73-2.42 (m, 2.04H), 2.25-2.17 (m, 4.01H), 2.15-2.11 (m, 3.20H), 2.09-1.96 (m, 4.15H), 1.94-1.87 (m, 1.17H), 1.76-1.60 (m, 4.32H), 1.58-1.17 (m, 10.11H), 1.07-1.00 (m, 4.04H), 0.70-0.61 (m, 3.01H). 13 CNMR (101 MHz, CDC13, diastereomers): δ 209.6, 145.0, 144.8, 141.4, 139.2, 129.8, 129.8, 126.4, 126.0, 123.0, 121.0, 113.7, 113.5, 63.7, 57.0, 53.7, 50.4, 50.2, 48.4, 44.0, 40.1, 38.9, 38.9, 38.3, 37.7, 37.3, 37.0, 33.8, 31.9, 31.9, 31.8, 31.6, 29.7, 24.6, 24.5, 22.9, 21.1, 20.8, 20.4, 19.5, 19.0, 13.3, 13.2.

Claims

1. A process for the copper photocatalyzed amination of an unactivated halogenated hydrocarbon to produce a nitrogen alkylated compound, characterized in that Comprising the following steps, The carbon-nitrogen bond coupling is carried out by stirring under irradiation of LED lamp for 5-50 hours to obtain the nitrogen alkylation product; the reaction formula is as follows: The reaction temperature is 20-30℃, the molar ratio of copper salt to ligand is 1:1, the molar ratio of substrate nitrogen nucleophile, halogenated hydrocarbon and copper salt is 20:30:1, the concentration of base is 0.1M-0.2M, and the reaction time is 5-50 hours; ； It is further characterized in that the pyridine carbene ligand is shown in the following structural formula: in which formula X is a halogen atom; R 1 is a C1-C10 alkyl group, a C1-C10 haloalkyl group, a C1-C10 alkylacyl group, a C1-C10 alkylsulfonyl group, a C1-C10 alkoxycarbonyl group; R 2 is a hydrogen atom, a C1-C10 alkyl group; R 1 and R 2 are joined or not, in the joined case indole, carbazole, pyrrole, indazole; R 3 is a C1-C10 alkyl group, a C1-C10 haloalkyl group, a C1-C10 heteroatom-containing alkyl group; R 1 , R 2 may also be a phenyl group, a furanyl group, a thienyl group, a pyridyl group, a tolyl group, a p-trifluoromethylphenyl group, a p-methoxyphenyl group, a p-methyl-substituted benzoyl group, a 3-pyridylbenzoyl group; The copper salt is CuOAc, CuI, CuBr, CuCl, Cu(OAc)2, Cu(OTf)2, CuBr2, CuCl2. 。 2. The method of claim 1, further characterized by, 3. The method of claim 1, wherein the base is 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), tetramethylguanidine, 2-tert-butyl-1,1,3,3-tetramethylguanidine (BTMG), lithium tert-butoxide or sodium tert-butoxide. The wavelength range of the LED lamp is 365nm-800nm.

4. The method of claim 1, wherein ​

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