Nickel-catalyzed olefin asymmetric hydroamination and migration hydroamination method

Abstract

The invention discloses a method for respectively realizing asymmetric hydroamination and migration hydroamination of olefin by using nickel and ligand combined catalysis, and belongs to the field of organic chemistry and medicinal chemistry. Under the action of a metal nickel source, a chiral ligand, a hydrogen source, an additive and the like, olefin and azide amination reagents protected by different carbonates are used as amine sources to react in an organic solvent, and a series of chiral amine and alkylamine compounds are obtained with excellent enantioselectivity and good yield. Cheap transition metal nickel is used as a catalyst, simple and easily available alkene and carbonic ester protected azide amination reagents are used as raw materials, conditions are mild and simple, functional group compatibility is good, and operation is easy and convenient.

Description

Technical Field

[0001] The method of the invention belongs to the field of organic chemistry and medicinal chemistry, uses nickel and different ligand combinations to catalyze the asymmetric hydrogenation, migratory hydrogenation and migratory asymmetric hydrogenation of olefins, obtains important α-chiral benzylamine intermediates and alkylamine compounds, and has a very wide range of applications. Background Art

[0002] In the past two decades, high-yield metal hydrogen catalysis such as FeH, CoH and CuH has received continuous attention from synthetic chemists. In recent years, NiH catalysis has gradually become a hot topic for synthetic chemists. Since nickel is cheap and easy to obtain, has a variety of oxidation states, and has unique and extensive applications in the field of coupling chemistry, the corresponding NiH catalysis can achieve a variety of conversions of readily available olefins to obtain a series of high value-added products, which has attracted widespread attention from synthetic chemists.

[0003] α-Chiral amines are an important type of structural skeleton and are widely found in active pharmaceutical molecules and natural products. Due to their unique structure and high biological activity, these drugs have attracted widespread attention from chemists. In recent years, many methods for synthesizing α-chiral amine compounds have been developed, among which the hydroamination reaction of olefins is a typical synthetic strategy.

[0004] The reported asymmetric hydrogenation catalyzed by metal hydrogen mainly includes the following:

[0005] As early as 2013, the Buchwald group (S. Zhu, N. Niljianskul, S. L. Buchwald, J. Am. Chem. Soc. 2013, 135, 15746.) and the Miura group (Y. Miki, K. Hirano, T. Satoh, M. Miura, Angew. Chem. Int. Ed. 2013, 52, 10830.) developed a new method for synthesizing α-chiral amine compounds. They broadened the scope of application of copper-catalyzed olefin hydroamination reactions. The olefins can be terminal olefins, internal olefins, or electron-deficient olefins. In addition to dialkylhydroxylamine reagents, electrophilic dioxazolone amide reagents are also applicable.

[0006]

[0007] In 2020, Lu Zhan's research group (X.Shen, X.Chen, J.Chen, Y.Sun, Z.Cheng, Z.Lu, Nat. Commun. 2020, 11, 783.) developed a CoH-catalyzed amination strategy for olefins and aromatic azo esters with good functional group tolerance and high Markovnikov selectivity. On this basis, amides or primary amine compounds can be further obtained through multi-step derivatization experiments.

[0008]

[0009] In addition to Cu, Fe and Co, the hydroamination of olefins catalyzed by abundant metals, Ni-catalyzed hydroamination of olefins has also developed rapidly. Our group has conducted some research on NiH-catalyzed hydroamination of olefins.

[0010] In 2018, Zhu Shaolin's group (J. Xiao, Y. He, F. Ye, S. Zhu, Chem 2018, 4, 1645.) directly used nitroaromatics as amine sources and achieved remote C(sp3)–H bond direct amination to prepare aromatic amine derivatives through nickel-catalyzed remote hydrogenation reaction.

[0011]

[0012] In 2020, the research group of Shaolin Zhu (Y. Zhang, J. He, P. Song, Y. Wang, S. Zhu, CCS Chem. 2020, 2, 2259.) further achieved selective amination of highly active benzyl sites and terminal sites with minimal steric hindrance by regulating ligands using phosphine ligands and nitrogen ligands respectively. By using metal nickel catalysts, combined with silicon hydride as a hydrogen source and a reducing agent, starting from distal and proximal olefins and a mixture of olefin isomers, the regional divergent remote hydrogenation reaction of olefins by alkylhydroxylamine reagents was achieved.

[0013]

[0014] In 2021, Zhu Shaolin's research group (L. Meng, J. Yang, M. Duan, Y. Wang, S. Zhu, Angew. Chem. Int. Ed. 2021, 60, 23584.) used the simple and easy-to-synthesize N,N-Biox ligand to achieve asymmetric hydroarylation, hydroalkylation and hydroamidation of olefins, respectively, with a wide range of substrate applicability.

[0015]

[0016] In 2023, Ding Kuiling's research group (C. Wang, X. Wang, Z. Wang, K. Ding, Org. Lett. 2023, 25, 6577.) developed a nickel-catalyzed enantioselective hydroamination reaction of vinyl aromatics. Under the regulation of the SKP ligand, a variety of α-branched chiral alkylamines were prepared in high yields with high regioselectivity and excellent enantioselectivity.

[0017]

[0018] In the olefin hydroamination reaction developed in recent years, the types of olefins are relatively wide, which can be non-activated olefins or activated in-situ olefins. Through the regulation of ligands, the reaction site can occur in-situ, migrate to the terminal position, or migrate to the more active benzyl position. Compared with CuH catalysis, the advantage of NiH catalysis is that it has a wider range of olefins. In addition to realizing in-situ hydroamination reactions, it can also realize migrated hydroamination reactions. At the same time, the range of electrophilic amination agents is wider. For example, nitroaromatics are only suitable for NiH catalysis, which has not yet been realized by CuH catalysis.

[0019] Zhu Shaolin's research group at Nanjing University has long been committed to nickel-hydrogen catalytic chemistry, achieving the (migratory) asymmetric hydrogen functionalization of a series of olefins, selectively introducing aromatic, alkyl and other functional groups, and further regulating the enantioselectivity of the reaction through chiral ligands. Summary of the invention

[0020] The purpose of the present invention is to provide a nickel-catalyzed asymmetric hydrogenation and migration hydrogenation method for olefins, which has cheap and readily available raw materials, is easy to operate, has a wide substrate range and good functional group compatibility, and has excellent enantioselectivity and good yield. The nickel-hydrogen catalyzed hydrogenation method for olefins of the present invention only needs to use different ligands for regulation, and can respectively realize asymmetric hydrogenation, migration hydrogenation and migration asymmetric hydrogenation of olefins, has a wide range of substrate applications, and provides a new and efficient method for the synthesis of chiral amines and alkylamines.

[0021] The present invention achieves one of the above-mentioned purposes by adopting the following technical scheme: A method for asymmetric hydrogenation of olefins catalyzed by nickel comprises the following steps: in an inert gas, a metal nickel catalyst, a chiral ligand L*, a hydrogen source, and an additive are dissolved in an organic solvent, and then an aromatic olefin is added. or aryl substituted remote olefins or olefins containing a carbonyl directing group or alkyl olefins or α-acrylate substituted olefin and azidation reagent N 3–PG is used as an amine source to obtain a reaction mixture, which is then purified to obtain the target enantiomer-enriched α-aryl-substituted chiral amine product ( or its enantiomer ) or the migration of chiral amine products ( or its enantiomer ) or the chiral amine product containing a carbonyl directing group ( or its enantiomer )or( or its enantiomer ) or alkylamine compounds Or an in situ chiral amine product containing an α-substituted acrylate ( or its enantiomer );

[0022] Among them, R 1 , R 2 is a terminal substituent of an olefin, which is any one of a hydrogen atom, an alkyl group, an aryl group, an ester group, an amide group, an amine group, a protected amine group, and a silyl ether;

[0023] R 3 , R 4 , R 5 , R 6 and R 7 The structure is one of aryl (Aryl), alkyl (Alkyl) or hydrogen atom (H);

[0024] Ar is a substituted aryl or heteroaryl group;

[0025] PG is a carbonate protecting group or p-toluenesulfonyl or diphenylphosphonic acid group;

[0026] The achiral ligand L is any one of the following:

[0027]

[0028] The chiral ligand L* is any one of the following:

[0029]

[0030] The nickel-catalyzed asymmetric hydroamination of olefins can be prepared by any of the following routes: wherein Preparation Route 1:

[0031]

[0032] Preparation route 2:

[0033]

[0034] Preparation route 3:

[0035]

[0036] Preparation route 4:

[0037]

[0038] Preparation route 5:

[0039]

[0040] Preparation route 6:

[0041]

[0042] The chiral ligand L1 * It is a Biox ligand with the structural formula: or its enantiomer or chiral ligand L5 * for or its enantiomer or chiral ligand L6 * Box ligand or its enantiomer Or the chiral ligand L7 is a Pyrox ligand, and the structural formula is: Its enantiomer or its racemic ligand (±) Preferably, preparation route 1:

[0043]

[0044] The molar ratio of olefin 1 to amine source 2 in route 1 is 2.5:1, and NiBr 2 ·DME is a nickel catalyst nickel bromide (II) ·Ethylene glycol dimethyl ether, chiral ligand L1* is or its enantiomer HBpin is the hydrogen source pinacol borane, PCy 3 Tricyclohexylphosphine is an additive, LiI is an additive, Molecular sieve is used as dehydrating agent and toluene is used as solvent;

[0045] Preparation route 2:

[0046]

[0047] The molar ratio of olefin 5 to amine source 2 in route 2 is 2:1, Ni(ClO 4 ) 2 6H 2 O is a nickel catalyst nickel perchlorate (II) hexahydrate, and the chiral ligand L5* is or its enantiomer HBpin is the hydrogen source pinacol borane, LiPF 6 As the additive lithium hexafluorophosphate, Molecular sieves are water removal agents, and THF is tetrahydrofuran solvent;

[0048] Preparation route 3:

[0049]

[0050] The molar ratio of olefin 7 and amine source 2 in route 3 is 2:1, NiCl 2 ·(PCy 3)2 The nickel catalyst is bis(tricyclohexylphosphine)nickel dichloride, and the ligand L6* is or its enantiomer HBpin is the hydrogen source pinacol borane, THF is the solvent tetrahydrofuran;

[0051] Preparation route 4:

[0052]

[0053] The molar ratio of olefin 9 to amine source 2 in route 4 is 2:1, NiCl 2 ·(PCy 3)2 The nickel catalyst is bis(tricyclohexylphosphine)nickel dichloride, and the ligand L6* is or its enantiomer HBpin is the hydrogen source pinacol borane, THF is the solvent tetrahydrofuran;

[0054] Preparation route 5:

[0055]

[0056] The molar ratio of olefin 11 to amine source 2 in route 5 is 2:1. 2 The nickel catalyst is nickel iodide, and the ligand (±)L7 is HBpin is the hydrogen source pinacol borane, KI is the additive potassium iodide, Molecular sieve is a water removal agent, CHCl 3 The solvent is chloroform;

[0057] Preparation route 6:

[0058]

[0059] The molar ratio of olefin 13 and amine source 2 in route 6 is 2:1, NiI 2 It is a nickel catalyst nickel iodide, and the ligand (S,S)-L7* is HBpin is the hydrogen source pinacol borane, KI is the additive potassium iodide, MS molecular sieve as water removal agent Molecular sieve, CHCl 3 The solvent is chloroform;

[0060] Preferably, the metal nickel salt is any one of nickel chloride, nickel chloride hexahydrate, nickel chloride ethylene glycol dimethyl ether complex, nickel bromide, nickel bromide trihydrate, nickel bromide diethylene glycol dimethyl ether complex, nickel bromide ethylene glycol dimethyl ether complex, nickel iodide, nickel iodide hexahydrate, bis-(1,5-cyclooctadiene) nickel complex, nickel nitrate hexahydrate, nickel perchlorate hexahydrate, and nickel tetrafluoroborate hexahydrate;

[0061] The additive is one or more of lithium chloride, sodium chloride, lithium bromide, potassium bromide, magnesium bromide, magnesium bromide hydrate, lithium iodide, sodium iodide, zinc iodide, magnesium iodide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, sodium acetate, potassium acetate, methanol, isopropanol, tert-butanol, hexafluoroisopropanol, benzyl alcohol, acetonitrile, tricyclohexylphosphine, triphenylphosphine, and lithium hexafluorophosphate.

[0062] The solvent is one or more of tetrahydrofuran, 1,4-dioxane, toluene, dichloromethane, chloroform, N-methylpyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide.

[0063] The aromatic olefin is a trans-configuration olefin, and its structural formula is as follows: Beneficial effects:

[0064] 1. The reaction temperature is -10°C to 50°C, the reaction conditions are mild, the reaction effect is good, and the product can be obtained with excellent yield and enantioselectivity.

[0065] 2. The olefins are cheap, commercially available, or have a simple synthesis route.

[0066] 3. The nickel-catalyzed olefin hydroamination reaction can realize asymmetric hydroamination, migratory asymmetric hydroamination and migratory (in situ) hydroamination respectively through the regulation of ligands, and has a wide range of applications.

[0067] 4. The chiral ligand L * Function: Coordinate with metallic nickel to control chirality during the reaction, and the process of adding nickel-hydrogen to olefins is irreversible. Once nickel-hydrogen is added to olefins, no further β-H elimination or homolytic cleavage reaction will occur.

[0068] 5. The olefin can be trans, cis, or a mixture of cis and trans, but when the olefin is pure trans, the enantioselectivity of the target product is optimal. It can be seen from Examples 1 and 18 that the configuration reaction effects of different olefins are quite different, and the trans-configuration olefin has a better enantioselectivity than the cis-configuration olefin. The aryl olefin of the present invention is a trans-configuration.

[0069] 6. The hydrogen source is all provided by pinacol borane, and other silicon hydrogen reagents have unsatisfactory effects. In route 1-6, when polymethyl hydrogen siloxane (PMHS), trimethoxysilane, diethoxymethyl silane (DEMS) and phenyl silane are used to replace pinacol borane, no target product is generated. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] The present invention will be further described below in conjunction with the accompanying drawings.

[0071] Figure 1 is the H spectrum of the product of Example 1;

[0072] Figure 2 is the C spectrum of the product of Example 1;

[0073] Figure 3 is the H spectrum of the product of Example 7;

[0074] Figure 4 is the C spectrum of the product of Example 7;

[0075] Figure 5 is the H spectrum of the product of Example 14;

[0076] Figure 6 is the C spectrum of the product of Example 14;

[0077] Figure 7 is the B spectrum of the product of Example 14;

[0078] Figure 8 is the H spectrum of the product of Example 18;

[0079] Fig. 9 is the C spectrum of the product of Example 18;

[0080] Fig.10 is the H spectrum of the product of Example 22;

[0081] Fig.11 is the C spectrum of the product of Example 22;

[0082] Fig.12 is the P spectrum of the product of Example 22;

[0083] Fig.13 is the H spectrum of the product of Example 23;

[0084] Fig.14is the C spectrum of the product of Example 23;

[0085] Fig.15 This is the H spectrum of the product of Example 25.

[0086] Fig.16 is the C spectrum of the product of Example 25;

[0087] Fig.17 This is the H spectrum of the product of Example 26.

[0088] Fig.18 is the C spectrum of the product of Example 26;

[0089] Fig.19 This is the H spectrum of the product of Example 27.

[0090] Fig. 20 is the C spectrum of the product of Example 27;

[0091] Fig.21 This is the H spectrum of the product of Example 33.

[0092] Fig. 22 is the C spectrum of the product of Example 33;

[0093] Fig.23 This is the H spectrum of the product of Example 45.

[0094] Fig.24 is the P spectrum of the product of Example 45;

[0095] Fig.25 This is the C spectrum of the product of Example 45.

[0096] Fig.26 is the H spectrum of the product of Example 49;

[0097] Fig. 27 is the C spectrum of the product of Example 49; DETAILED DESCRIPTION

[0098] The features and advantages of the present invention can be further understood through the following detailed description. The examples provided are merely illustrative of the method of the present invention and are not intended to limit the remainder of the present invention in any way.

[0099] In the following examples, TBS refers to NiBr 2 DME refers to ethylene glycol dimethyl ether nickel bromide, Ni(BF 4 ) 2 6H 2 O refers to nickel tetrafluoroborate hexahydrate, NiCl 2 6H 2 O refers to nickel chloride hexahydrate, Ni(NO 3 ) 2 6H2 O refers to nickel nitrate hexahydrate, Ni(ClO 4 ) 2 6H 2 O refers to nickel perchlorate (II) hexahydrate, NiI 2 refers to nickel iodide, HBpin refers to pinacol borane, Toluene refers to toluene, 1,4-dioxane refers to 1,4-dioxane, THF refers to tetrahydrofuran, equiv refers to equivalent number, L * Ligand is One of them.

[0100] Example 1

[0101]

[0102] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1a, 29.6 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (49.1 mg, white solid, yield 82%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (94%).

[0103] 1 H NMR (400 MHz, CDCl 3 )δ7.45–7.03(m,7H),6.90–6.81(m,2H),5.16–4.98(m,3H),4.62–4.47(m,1H),3.80(s,3H),1.85–1.69(m,2H),0.88(t,J=7.4Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ158.9,155.9,136.7,134.6,130.5,128.6,128.2,127.7,114.1,66.8,56.5,55.4,29.7,10.8; HRMS(ESI)calcd.for C18 H 22 NO 3 [M+H] + m / z 300.1594, found 300.1584; mp79.6–80.6℃; IR(neat,cm -1 )3314,2963,1684,1512,1240,1031,817,696,535;[α] D 27 =–36.4(c=1.16,CHCl 3 );94%ee;HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=13.7min,t R (major) = 19.6min.

[0104] The solvent described in Example 1 is toluene. When DMAc (N,N-dimethylacetamide) is used instead of toluene, both the yield and the enantioselectivity decrease, with the yield decreasing from 82% to 30% and the enantioselectivity decreasing from 94% to 90%.

[0105] Example 2

[0106]

[0107] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1b, 32.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (37.8 mg, white solid, yield 60%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (91%).

[0108] 1 H NMR (500 MHz, CDCl 3 )δ7.43–7.27(m,5H),7.24–7.13(m,4H),5.14–4.99(m,3H),4.61–4.47(m,1H),2.47(s,3H),1.82–1.71(m,2H),0.89(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ155.8,139.5,137.4,136.6,128.6,128.3,127.1,127.0,66.9,56.6,29.6,16.1,10.8; HRMS(ESI)calcd.for C 18 H 22 NO 2 S[M+H] + m / z316.1366, found 316.1358; mp98.3–99.3℃; IR(neat,cm -1 )3313,2930,1681,1532,1237,1043,853,697,511;[α] D 27 =–38.5(c=0.90,CHCl 3 );91%ee;HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=14.3min,t R (major) = 19.3min.

[0109] Example 3

[0110]

[0111] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1c, 42.0 mg, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the lid of the reaction tube, and react at 10°C for 36 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (49.2 mg, white solid, yield 68%) is separated and purified by column chromatography, and the ee value of the target product is measured (91%). 1 H NMR (500 MHz, CDCl 3 )δ7.41–7.26(m,7H),7.25–7.17(m,2H),7.14–7.09(m,1H),7.05–6.93(m,4H), 5.18–4.98(m,3H),4.67–4.50(m,1H),1.86–1.74(m,2H),0.92(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ157.3,156.5,155.9,137.4,136.6,129.8,128.6,128.2,127.9,123.4,119.0,119.0,66.9,56.5,29.7,10.8; HRMS(ESI)calcd.forC 23 H 23 NO 3 Na[M+Na] + m / z 384.1570, found 384.1559; mp84.2–85.0℃; IR(neat,cm -1 )3343,2930,1683,1505,1226,1077,839,692,529;[α] D 27 =–31.1(c=1.26,CHCl 3 ); 91% ee; HPLC analysis IG-3column,n-hexane / iso-propanol=90 / 10,flow rate 1.0mL / min,220nm UV detector,t R (minor)=16.2min,t R (major) = 22.1min.

[0112] Example 4

[0113]

[0114] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1d, 49.6 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (55.8 mg, white solid, yield 70%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (91%). 1 H NMR (500 MHz, CDCl 3 )δ7.43–7.28(m,5H),7.15–7.06(m,2H),6.83–6.76(m,2H),5.15–4.92(m,3H),4.6 2–4.48(m,1H),1.85–1.71(m,2H),0.99(s,9H),0.87(t,J=7.4Hz,3H),0.20(s,6H); 13 C NMR (126 MHz, CDCl 3 )δ155.9,154.9,136.7,135.1,128.6,128.3,128.2,127.6,120.2,66.8,56.5,29.7,25.8,18.3,10.8,-4.3; HRMS(ESI)calcd.forC 23 H 33 NNaO 3 Si[M+Na] + m / z 422.2122, found 422.2112; mp50.2–50.8℃; IR(neat,cm -1 )3304,2929,1688,1509,1248,1041,835,688,523;[α] D 27 =–26.7(c=1.15,CHCl 3 );91%ee;HPLC analysis AD-H column,n-hexane / iso-propanol=90 / 10,flow rate1.0mL / min,220nm UV detector,t R (minor)=5.0min,t R (major) = 5.9min.

[0115] Example 5

[0116]

[0117] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1e, 35.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (45.8 mg, white solid, yield 70%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (93%). 1 H NMR (400 MHz, CDCl 3 )δ7.45–7.15(m,7H),7.08–7.01(m,2H),5.14–5.01(m,3H),4.67–4.54(m,1H),2.29(s,3H),1.82–1.72(m,2H),0.90(t,J=7.4Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ169.6,155.9,149.9,140.1,136.5,130.5,128.6,128.2,127.6,121.7,66.9,56.5,29.6,21.2,10.8; HRMS(ESI)calcd.for C 19 H 21 NO 4 Na[M+Na] +m / z 350.1363, found 350.1353; mp110.3–111.3℃; IR(neat,cm -1 )3319,2929,1751,1686,1537,1225,1083,855,697,527;[α] D 27 =–28.9(c=0.88,CHCl 3 );93%ee;HPLC analysis IG-3column,n-hexane / iso-propanol=90 / 10,flow rate 1.0mL / min,220nm UV detector,t R (minor)=27.0min,t R (major) = 29.2min.

[0118] Example 6

[0119]

[0120] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1f, 34.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (54.0 mg, colorless oil, yield 83%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (92%). 1 H NMR (500 MHz, CDCl 3 )δ7.39–7.27(m,7H),7.23–7.16(m,2H),5.16–5.00(m,3H),4.65–4.56(m,1H),1.88–1.75(m,2H),1.32(s,9H),0.91(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3)δ155.9,150.2,139.4,136.7,128.6,128.3,128.2,126.2,125.6,66.8,56.6,34.6,31.5,29.7,10.9; HRMS(ESI)calcd.for C 21 H 27 NO 2 Na[M+Na] + m / z 348.1934,found 348.1925;IR(neat,cm -1 )3323,2963,1696,1528,1233,1043,833,697,570;[α] D 27 =–30.5(c=1.03,CHCl 3 );92%ee;HPLC analysis IA column, n-hexane / iso-propanol=95 / 5, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=9.8min,t R (major) = 11.9min.

[0121] Example 7

[0122]

[0123] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1 g, 23.6 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the lid of the reaction tube, and react at 10°C for 36 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (40.3 mg, white solid, yield 75%) is separated and purified by column chromatography, and the ee value of the target product is measured (90%). 1 H NMR (500 MHz, CDCl 3)δ7.40–7.30(m,6H),7.30–7.17(m,4H),5.15–4.95(m,3H),4.66–4.54(m,1H),1.86–1.72(m,2H),0.90(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ155.9,142.5,136.6,129.6,128.7,128.6,128.3,127.4,126.5,66.9,57.0,29.8,10.8; HRMS(ESI)calcd.for C 17 H 19 NO 2 Na[M+Na] + m / z 292.1308, found 292.1300; mp57.5–57.7℃; IR(neat,cm -1 )3339,2929,1684,1522,1231,1037,844,694,523;[α] D 27 =–29.1(c=0.74,CHCl 3 );90%ee;HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=11.6min,t R (major) = 14.4min.

[0124] Example 8

[0125]

[0126] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1h, 38.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (38.7 mg, white solid, yield 56%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (91%). 1 H NMR (400 MHz, CDCl 3 )δ7.62–7.55(m,4H),7.47–7.42(m,2H),7.42–7.11(m,8H),5.17–5.02(m,3H),4.72–4.58(m,1H),1.89–1.78(m,2H),0.94(t,J=7.4Hz,3H); 13 CNMR (101MHz, CDCl 3 )δ156.0,141.6,140.9,140.4,136.6,128.9,128.7,128.3,127.5,127.4,127.2,127.0,66.9,56.8,29.8,10.8; HRMS(ESI)calcd.for C 23 H 23 NO 2 Na[M+Na] + m / z368.1621, found 368.1611; mp122.6–123.1℃; IR(neat,cm -1 )3311,2924,1683,1532,1240,1042,838,695,506;[α] D 27 =–32.6(c=0.65,CHCl 3 );91%ee;HPLC analysis OD-H column,n-hexane / iso-propanol=90 / 10,flow rate 1.0mL / min,220nmUV detector,t R (minor)=13.9min,t R (major) = 17.9 min.

[0127] Example 9

[0128]

[0129] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1i, 35.6 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the lid of the reaction tube, and react at 10°C for 36 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (46.1 mg, white solid, yield 70%) is obtained by column chromatography separation and purification, and the ee value of the target product is measured (94%). 1 H NMR (400 MHz, CDCl 3 )δ7.39–7.27(m,5H),6.86–6.70(m,3H),5.14–4.99(m,3H),4.59–4.46(m,1H),3.85(s,6H),1.83–1.69(m,2H),0.89(t,J=7.3Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ155.9,149.2,148.4,136.7,135.3,128.6,128.2,118.5,111.4,110.1,66.8,56.9,56.0,56.0,29.7,10.8; HRMS(ESI)calcd.for C 19 H 23 NO 4 Na[M+Na] + m / z352.1519, found 352.1510; mp103.1–103.8℃; IR(neat,cm -1 )3349,2932,1697,1513,1230,1022,817,692,544;[α] D 27 =–31.5(c=1.11,CHCl 3 );94%ee;HPLC analysis OD-H column,n-hexane / iso-propanol=90 / 10,flow rate 1.0mL / min,220nmUV detector,t R (minor)=17.0min,t R (major) = 21.8min.

[0130] Example 10

[0131]

[0132] Under nitrogen atmosphere, nickel nitrate hexahydrate (4.7 mg, 8 mol%) and chiral ligand L1 were added to the reaction tube. * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1j, 35.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (44.5 mg, colorless oil, yield 68%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (92%). 1 H NMR (500 MHz, CDCl 3 )δ7.46–7.28(m,5H),6.75(s,3H),5.93(s,2H),5.15–4.99(m,3H),4.64– 4.49(m,1H),1.74–1.63(m,2H),1.36–1.24(m,2H),0.91(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ155.8,147.9,146.8,136.9,136.6,128.6,128.3,128.2,119.8,108.4,106.9,101.1,66.8,55.2,39.0,19.5,13.9; HRMS(ESI)calcd.for C 19 H 21 NO 4 Na[M+Na] +m / z 350.1363, found 350.1353; mp57.8–58.8℃; IR(neat,cm -1 )3320,2960,1691,1491,1443,1241,1038,933,698;[α] D 25 =32.0(c=1.08,CHCl 3 ); 92% ee; HPLC analysis OD-H column,n-hexane / iso-propanol=95 / 5,flow rate 0.8mL / min,220nm UV detector,t R (minor)=24.5min,t R (major) = 30.4min.

[0133] Embodiment 11

[0134]

[0135] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1k, 27.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (35.6 mg, white solid, yield 62%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (91%). 1 H NMR (400 MHz, CDCl 3 )δ7.39–7.15(m,7H),7.06–6.95(m,2H),5.15–4.94(m,3H),4.63–4.46(m,1H),1.85–1.70(m,2H),0.89(t,J=7.4Hz,3H); 19 F NMR (376 MHz, CDCl 3 )δ-115.50;13 C NMR (101 MHz, CDCl 3 )δ162.1(d,J=246.4Hz),155.9,138.4,136.6,128.6,128.3,128.2,128.1,115.5(d,J=22.2Hz),67.0,56.5,29.8,10.7; HRMS(ESI)calcd.forC 17 H 18 FNO 2 Na[M+Na] + m / z 310.1214, found 310.1207; mp88.9–90.6℃; IR(neat,cm -1 )3307,2936,1687,1544,1219,1045,827,697,527;[α] D 27 =–25.3(c=1.01,CHCl 3 );91%ee;HPLC analysis OD-H column,n-hexane / iso-propanol=90 / 10,flow rate1.0mL / min,220nm UV detector,t R (minor)=8.2min,t R (major) = 9.8min.

[0136] Example 12

[0137]

[0138] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1 l, 37.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (49.9 mg, white solid, yield 74%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (88%). 1 H NMR (400 MHz, CDCl 3 )δ7.61(d,J=7.8Hz,2H),7.51–7.22(m,7H),5.15–5.03(m,3H),4.74–4.59(m,1H),1.86–1.77(m,2H),0.93(t,J=7.4Hz,3H); 19 F NMR (376 MHz, CDCl 3 )δ-62.47; 13 C NMR (126 MHz, CDCl 3 )δ155.9,146.7,136.4,134.7(q,J=31.5Hz),128.7,128.4,126.8,125.7(q,J =3.8Hz),124.3(q,J=272.2Hz),67.1,56.7,29.7,10.7; HRMS(ESI)calcd.for C 18 H 18 F 3 NO 2 Na[M+Na] + m / z 360.1182, found 360.1172; mp102.4–103.4℃; IR(neat,cm -1 )3304,2921,1686,1542,1265,1044,823,697,521;[α] D 27 =–13.5(c=0.96,CHCl 3 ); 88% ee; HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=8.2min,t R (major) = 10.6min.

[0139] Example 13

[0140]

[0141] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1 m, 35.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (45.3 mg, white solid, yield 69%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (92%). 1 H NMR (400 MHz, CDCl 3 )δ7.98–7.90(m,2H),7.51–7.23(m,7H),5.17(s,1H),5.12–5.01(m,2H), 4.72–4.58(m,1H),3.91(s,3H),1.84–1.76(m,2H),0.89(t,J=7.4Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ167.1,155.9,143.1,136.5,131.4,130.6,128.7,128.7,128.6,128.3,127.4,67.0,56.8,52.3,29.8,10.7; HRMS(ESI)calcd.for C 19 H 21 NO 4 Na[M+Na] + m / z 350.1363, found 350.1353; mp83.5–84.9℃; IR(neat,cm -1 )3342,2946,1715,1682,1523,1275,1086,751,696,546;[α] D 26 =–29.6(c=1.27,CHCl 3 ); 92% ee; HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=20.4min,t R (major) = 25.5min.

[0142] Embodiment 14

[0143]

[0144] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1n, 48.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (52.2 mg, white solid, yield 66%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (91%). 1 H NMR (500 MHz, CDCl 3 )δ7.74–7.68(m,2H),7.41–7.26(m,7H),5.14–5.01(m,3H),4.65–4.55(m,1H),1.85–1.75(m,2H),1.35(s,12H),0.89(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ155.8,141.8,136.6,134.0,132.5,129.8,128.6,128.3,128.2,128.1,84.0,66.8,57.2,30.0,25.0,25.0,10.9; 11 B NMR (160MHz, CDCl 3 )δ35.91; HRMS(ESI)calcd.for C 23 H 30 BnN4 [M+Na] + m / z 418.2160, found 418.2150; mp124.8–125.7℃; IR(neat,cm -1 )3316,2974,1689,1536,1238,1039,852,678,544;[α] D 26 =–26.7(c=1.19,CHCl 3 );91%ee;HPLC analysis IA column, n-hexane / iso-propanol=98 / 2, flow rate 0.8mL / min, 220nm UV detector, t R (minor)=14.9min,t R (major) = 19.7min.

[0145] Embodiment 15

[0146]

[0147] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1n, 27.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 0°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (31.6 mg, white solid, yield 55%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (90%). 1 H NMR (500 MHz, CDCl 3 )δ7.38–7.30(m,7H),6.32(s,1H),5.14–5.07(m,2H),4.83(s,1H),4.72– 4.63(m,1H),1.76–1.68(m,2H),1.38–1.29(m,4H),0.89(t,J=6.8Hz,3H);13 CNMR (126MHz, CDCl 3 )δ155.9,143.5,139.2,136.6,128.7,128.3,128.3,127.2,109.0,66.9,47.5,35.4,28.2,22.5,14.1; HRMS(ESI)calcd.for C 17 H 21 NO 3 Na[M+Na] + m / z 310.1413, found 310.1406; mp113.8–114.3℃; IR(neat,cm -1 )3303,2954,1682,1544,1256,1053,777,695,580;[α] D 26 =–30.5(c=0.42,CHCl 3 );90%ee;HPLC analysis ICcolumn,n-hexane / iso-propanol=98 / 2,flow rate 1.0mL / min,220nm UV detector,t R (minor)=13.9min,t R (major) = 18.8min.

[0148] Example 16

[0149]

[0150] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1p, 33.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (33.0 mg, white solid, yield 52%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (87%). 1 H NMR (500 MHz, CDCl 3 )δ7.42–7.29(m,5H),7.29–7.27(m,1H),7.11(s,1H),7.00(d,J=5.0Hz,1H),5.16–5.05(m ,2H),4.91(s,1H),4.84–4.74(m,1H),1.78(s,2H),1.36–1.24(m,6H),0.90–0.83(m,3H); 13 C NMR (126 MHz, CDCl 3 )δ155.9,136.6,128.7,128.3,126.3,126.2,121.0,66.9,51.3,36.3,31.6,25.8,22.6,14.1; HRMS(ESI)calcd.forC 18 H 23 NO 2 SNa[M+Na] + m / z 340.1341, found 340.1334; mp64.2–64.6℃; IR(neat,cm -1 )3325,2919,1682,1529,1247,1051,836,695,576;[α] D 26 =–27.9(c=0.33,CHCl 3 ); 87% ee; HPLC analysis IC column, n-hexane / iso-propanol=95 / 5, flow rate 0.8mL / min, 220nm UV detector, t R (minor)=11.8min,t R (major) = 15.2min.

[0151] Embodiment 17

[0152]

[0153] Under nitrogen atmosphere, ethylene glycol dimethyl ether nickel bromide (5.0 mg, 8 mol%), chiral ligand L1 * (7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (10 mg) were dissolved in 1.2 mL of dry toluene and stirred at 25 °C for 10 minutes before adding the above olefin (1q, 29.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 88.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (64 mg, 0.50 mmol, 2.5 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (39.1 mg, colorless oil, yield 65%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (90%). 1 H NMR (400 MHz, CDCl 3 )δ8.09(s,1H),7.47(d,J=8.6Hz,1H),7.39–7.19(m,5H),6.71(d,J=8.6Hz,1H),5.12– 5.01(m,3H),4.62–4.47(m,1H),3.92(s,3H),1.84–1.70(m,2H),0.89(t,J=7.3Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ163.6,155.8,145.1,137.2,136.4,130.7,128.6,128.3,111.0,67.0,54.4,53.6,29.3,10.7; HRMS(ESI)calcd.forC 17 H 21 N 2 O 3 [M+H] + m / z 301.1547,found 301.1536;IR(neat,cm -1 )3324,2966,1695,1494,1284,1028,831,698;[α] D 26 =–24.6(c=1.42,CHCl 3 );90%ee;HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UVdetector, t R (minor)=16.1min,t R (major) = 21.2min.

[0154] Embodiment 18

[0155]

[0156] Under nitrogen atmosphere, nickel chloride hexahydrate (2.4 mg, 5 mol%) and chiral ligand L1 were added to the reaction tube. * (4.5mg, 7mol%), potassium iodide (3.3mg, 0.020mmol), Molecular sieves (10 mg) were dissolved in 1.0 mL of dry 1,4-dioxane and stirred at 25 °C for 10 minutes before adding the above olefin (1r, 26.0 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.50 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (38.2 mg, colorless oil, yield 68%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (85%). 1 H NMR (500 MHz, CDCl 3 )δ7.44–7.29(m,6H),7.21–7.06(m,3H),5.26–5.12(m,2H),5.06–4.79(m,2H),2.85–2.71(m,2H),2.12–2.02(m,1H),1.90–1.79(m,3H); 13 C NMR (126 MHz, CDCl 3 )δ156.0,137.5,136.8,136.7,129.2,128.8,128.7,128.2,127.4,126.3,66.8,49.4,30.6,29.3,20.0; HRMS(ESI)calcd.for C 18 H 19 NO 2 Na[M+Na] + m / z304.1308, found 304.1299; mp70.5–71.5℃; IR(neat,cm-1 )3320,2940,1685,1514,1238,1065,695,450;[α] D 26 =–26.9(c=0.89,CHCl 3 ); 85% ee; HPLC analysis AD-H column,n-hexane / iso-propanol=90 / 10,flowrate 1.0mL / min,220nm UV detector,t R (minor)=9.1min,t R (major) = 10.6min.

[0157] Embodiment 19

[0158]

[0159] Under nitrogen atmosphere, nickel nitrate hexahydrate (4.7 mg, 8 mol%) and chiral ligand L1 were added to the reaction tube. * (6.3 mg, 10 mol%), potassium iodide (5.0 mg, 0.030 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (6 mg) were dissolved in 1.0 mL of dry 1,4-dioxane and stirred at 25 °C for 10 minutes before adding the above olefin (1a, 29.6 mg, 0.20 mmol, 1.0 equiv), BocN 3 (2b, 72 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (46 mg, 0.36 mmol, 1.8 equiv), cover the reaction tube, and react at 10°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (37.2 mg, white solid, yield 70%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (91%). 1 H NMR (400 MHz, CDCl 3 )δ7.21–7.14(m,2H),6.88–6.82(m,2H),4.74(s,1H),4.46(s,1H),3.79(s,3H),1.79–1.69(m,2H),1.41(s,9H),0.87(t,J=7.4Hz,3H); 13 C NMR (101 MHz, CDCl 3)δ158.8,155.2,134.9,127.6,114.0,79.3,56.0,55.4,29.9,28.5,10.8; HRMS(ESI)calcd.for C 15 H 23 NO 3 Na[M+Na] + m / z288.1570, found 288.1562; mp105.5–106.0℃; IR(neat,cm -1 )3370,2972,1682,1513,1241,1034,827,627,538;[α] D 27 =–45.3(c=0.64,CHCl 3 );91%ee;HPLC analysis AD-H column, n-hexane / iso-propanol=99 / 1, flow rate 0.8mL / min, 220nm UV detector, t R (minor)=29.8min,t R (major) = 32.7 min.

[0160] Embodiment 20

[0161]

[0162] Under nitrogen atmosphere, nickel nitrate hexahydrate (4.7 mg, 8 mol%) and chiral ligand L1 were added to the reaction tube. * (6.3 mg, 10 mol%), potassium iodide (5.0 mg, 0.030 mmol), tricyclohexylphosphine (5.6 mg, 0.020 mmol), Molecular sieves (6 mg) were dissolved in 1.0 mL of dry 1,4-dioxane and stirred at 25 °C for 10 minutes before adding the above olefin (1a, 29.6 mg, 0.20 mmol, 1.0 equiv), CO 2 E 3 (2c, 57.5 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (46 mg, 0.36 mmol, 1.8 equiv), cover the reaction tube, and react at 10°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (34.2 mg, white solid, yield 72%) was obtained by column chromatography separation and purification. The ee value of the target product was measured (92%). 1 H NMR (500 MHz, CDCl 3)δ7.21–7.14(m,2H),6.88–6.84(m,2H),4.89(s,1H),4.60–4.42(m,1H),4.12–4.04( m,2H),3.79(s,3H),1.81–1.71(m,2H),1.21(t,J=7.1Hz,3H),0.88(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ158.8,156.1,134.9,127.7,114.0,60.8,56.3,55.4,29.7,14.7,10.8; HRMS(ESI)calcd.for C 13 H 19 NO 3 Na[M+Na] + m / z260.1257, found 260.1249; mp70.2–71.2℃; IR(neat,cm -1 )3336,2930,1686,1514,1235,1082,778,635,561;[α] D 27 =–58.1(c=0.93,CHCl 3 );92%ee;HPLC analysis OD-H column,n-hexane / iso-propanol=95 / 5,flow rate 0.8mL / min,220nm UV detector,t R (minor)=13.5min,t R (major) = 16.3min.

[0163] Embodiment 21

[0164]

[0165] Under nitrogen atmosphere, nickel nitrate hexahydrate (4.7 mg, 8 mol%) and chiral ligand L1 were added to the reaction tube. * (6.3 mg, 10 mol%), lithium iodide (2.7 mg, 0.020 mmol, 10 mol%), tricyclohexylphosphine (5.6 mg, 0.020 mmol, 10 mol%), Molecular sieves (10 mg) were dissolved in 1.0 mL of dry 1,4-dioxane and stirred at 25 °C for 10 minutes before adding the above olefin (1a, 29.6 mg, 0.20 mmol, 1.0 equiv), TrocN 3(2d, 43.4 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 10°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (34.2 mg, colorless oil, yield 50%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (94%). 1 H NMR (500 MHz, CDCl 3 )δ7.23–7.18(m,2H),6.89–6.85(m,2H),5.23–5.14(m,1H),4.77–4.62(m,2H ),4.59–4.52(m,1H),3.80(s,3H),1.90–1.77(m,2H),0.91(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ159.1,154.0,134.0,127.7,114.2,94.7,77.4,56.9,55.4,29.5,10.8; HRMS(ESI)calcd.for C 13 H 16 NO 3 Na[M+Na] + m / z362.0088,found 362.0078;IR(neat,cm -1 )3020,1734,1613,1510,1214,908,753,668;[α] D 25 =–44.2(c=0.53,CHCl 3 );94%ee;HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=8.9min,t R (major) = 10.3min.

[0166] Embodiment 22

[0167]

[0168] Under nitrogen atmosphere, nickel chloride hexahydrate (4.8 mg, 10 mol%) and chiral ligand L1 were added to the reaction tube. *(7.6 mg, 12 mol%), lithium iodide (2.7 mg, 0.020 mmol, 10 mol%), dissolved in dry 1.0 mL toluene / 1,4-dioxane (1:1, 0.5 mL + 0.5 mL), stirred at 25 ° C for 10 minutes, then added with the above olefin (1a, 29.6 mg, 0.20 mmol, 1.0 equiv), DPPA (2e, 137.6 mg, 0.50 mmol, 2.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), covered the lid of the reaction tube, and reacted at 15 ° C for 36 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and the target product (61.6 mg, colorless oil, yield 78%) was obtained by column chromatography separation and purification, and the ee value of the target product was measured (91%). 1 H NMR (500 MHz, CDCl 3 )δ7.31–7.27(m,2H),7.22–7.18(m,4H),7.16–7.07(m,4H),7.02–6.98(m,2H),6.80–6.77(m,2H ),4.28–4.21(m,1H),3.78(s,3H),3.72–3.66(m,1H),1.82–1.71(m,2H),0.79(t,J=7.4Hz,3H); 31 P NMR (202 MHz, CDCl 3 )δ-2.2; 13 C NMR (126 MHz, CDCl 3 )δ158.8,151.0(d,J=6.3Hz),151.0(d,J=7.6Hz),135.3(d,J=3.8Hz),129.6(d,J=23.9Hz),127.7,124.8(d,J=23 .9Hz),120.3(d,J=5.0Hz),120.2(d,J=5.0Hz),113.9,57.7,55.4,31.8(d,J=7.6Hz),10.7; HRMS(ESI)calcd.for C 22 H 25 NO 4 P[M+H] + m / z398.1516, found 398.1506; mp113.8–114.3℃; IR(neat,cm -1 )3350,2926,1613,1491,1195,1024,932,686,508;[α] D 27 =–36.1(c=1.35,CHCl 3);91%ee;HPLC analysis AD-Hcolumn,n-hexane / iso-propanol=80 / 20,flow rate 1.0mL / min,220nm UV detector,t R (minor)=11.9min,t R (major) = 13.9min.

[0169] Embodiment 23

[0170]

[0171] Under nitrogen atmosphere, nickel perchlorate (II) hexahydrate (7.3 mg, 0.020 mmol, 10 mol%), chiral ligand L5 (18.5 mg, 0.030 mmol, 15 mol%), and lithium hexafluorophosphate (91.1 mg, 0.60 mmol, 3.0 equiv) were added to the reaction tube. Molecular sieves (40 mg) were dissolved in 2.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (5a, 30 μL, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (87 μL, 0.60 mmol, 3.0 equiv), cover the lid of the reaction tube, and react at 30°C for 12 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (40.0 mg, white solid, yield 71%) was separated and purified by column chromatography, and the rr value (95:5) and ee value (90%) of the target product were measured. 1 H NMR (500 MHz, CDCl 3 )δ7.44–7.09(m,10H),5.16–4.94(m,3H),4.74–4.62(m,1H),1.84–1.66(m,2H),1.39–1.25(m,2H),0.92(t,J=7.4Hz,3H); 13 CNMR (126MHz, CDCl 3 )δ155.8,142.8,136.6,128.7,128.6,128.3,128.3,127.4,126.5,66.9,55.4,39.0,19.5,13.9; HRMS(ESI)calcd.for C 18 H 21 NO 2 Na[M+Na] +m / z 306.1464, found306.1457; mp79.5–80.4℃; IR(neat,cm -1 )3348,2960,2868,1683,1528,1250,1103,1023,757,698;[α] D 25 =26.4(c=1.00,CHCl 3 );90%ee;HPLC analysis AD-H column,n-hexane / iso-propanol=95 / 5,flow rate 0.8mL / min,210nm UV detector,t R (minor)=23.8min,t R (major) = 21.6min.

[0172] Embodiment 24

[0173]

[0174] Under nitrogen atmosphere, nickel perchlorate (II) hexahydrate (7.3 mg, 0.020 mmol, 10 mol%), chiral ligand L5 (18.5 mg, 0.030 mmol, 15 mol%), and lithium hexafluorophosphate (91.1 mg, 0.60 mmol, 3.0 equiv) were added to the reaction tube. Molecular sieves (40 mg) were dissolved in 2.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (5a, 30 μL, 0.20 mmol, 1.0 equiv), TsN 3 (2f, 78.9 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (87 μL, 0.60 mmol, 3.0 equiv), cover the lid of the reaction tube, and react at 30°C for 12 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (44.8 mg, white solid, yield 74%) was separated and purified by column chromatography, and the rr value (>99:1) and ee value (94%) of the target product were measured. 1 H NMR (500 MHz, CDCl 3)δ7.53(d,J=8.1Hz,2H),7.17–7.07(m,5H),7.03–6.97(m,2H),5.08(d,J=7.3Hz,1H),4.27 (q,J=7.4Hz,1H),2.35(s,3H),1.79–1.62(m,2H),1.31–1.12(m,2H),0.83(t,J=7.4Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ143.0,141.2,137.8,129.4,128.5,127.4,127.2,126.6,58.2,39.9,21.6,19.2,13.7; HRMS(ESI)calcd.for C 17 H 21 NNaO 2 S[M+Na] + m / z 326.1185, found 326.1182; mp99.5–100.5℃; IR(neat,cm -1 )3267,2928,1450,1317,1158,1093,701;[α] D 30 = +22.2 (c = 1.10, CHCl 3 );94%ee;HPLC analysis OD-H column,n-hexane / iso-propanol=80 / 20,flowrate 1.0mL / min,220nm UV detector,t R (major)=5.1min,t R (minor)=7.1min.

[0175] Embodiment 25

[0176]

[0177] Under nitrogen atmosphere, bis(tricyclohexylphosphine)nickel dichloride (13.8 mg, 0.020 mmol, 10 mol%) and chiral ligand L6 (14.4 mg, 0.024 mmol, 12 mol%) were added to the reaction tube and dissolved in 2.0 mL of dry tetrahydrofuran. After stirring at 25 °C for 10 minutes, the above olefin (7a, 32.2 mg, 0.20 mmol, 1.0 equiv) and CbzN were added. 3(2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the lid of the reaction tube, and react at 25°C for 24 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (55.0 mg, white solid, yield 88%) is separated and purified by column chromatography, and the rr value (93:7) and ee value (94%) of the target product are measured. 1 H NMR (500 MHz, CDCl 3 )δ9.88(s,1H),7.59–7.54(m,2H),7.35–7.23(m,8H),7.03–6.98(m,1H),4.99(s,2 H),4.03–3.92(m,1H),2.54–2.49(m,1H),2.40–2.35(m,1H),1.10(d,J=6.6Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ169.0,155.3,139.2,137.2,128.7,128.4,127.8,127.7,123.1,119.2,65.1,44.2,43.4,20.5; HRMS(ESI)calcd.for C 18 H 20 N 2 NaO 3 [M+Na] + m / z 335.1366, found335.1367; mp184.3–185.3℃; IR(neat,cm -1 )3297,1687,1657,1534,1444,1263,1059,757;[α] D 31 =+0.38 (c=0.66, MeOH); 94%ee; HPLC analysis AD-H column, n-hexane / iso-propanol=90 / 10, flow rate 1.0mL / min, 220nm UV detector, t R (minor)=10.7min,t R (major) = 15.4min.

[0178] Embodiment 26

[0179]

[0180] Under nitrogen atmosphere, bis(tricyclohexylphosphine)nickel dichloride (13.8 mg, 0.020 mmol, 10 mol%) and chiral ligand L6 (14.4 mg, 0.024 mmol, 12 mol%) were added to the reaction tube and dissolved in 2.0 mL of dry tetrahydrofuran. After stirring at 25 °C for 10 minutes, the above olefin (9a, 32.2 mg, 0.20 mmol, 1.0 equiv) and CbzN were added. 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 25°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (58.0 mg, white solid, yield 93%) was separated and purified by column chromatography. The rr value (>99:1) and ee value (96%) of the target product were measured. 1 H NMR (500 MHz, CDCl 3 )δ7.76(d,J=7.7Hz,2H),7.49–7.45(m,1H),7.41–7.35(m,2H),7.30–7.26(m,5H),7.22(s,1H), 5.30(d,J=7.8Hz,1H),5.05(s,2H),4.02–3.93(m,1H),3.53–3.42(m,2H),1.21(d,J=6.8Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ168.1,157.2,136.4,134.2,131.6,128.6,128.6,128.2,128.0,127.1,66.9,47.5,46.95,18.7; HRMS(ESI)calcd.for C 18 H 20 N 2 NaO 3 [M+Na] + m / z 335.1366, found 335.1357; mp155.4–156.4℃; IR(neat,cm -1 )3313,1689,1633,1541,1323,1268,1068,756;[α] D 31 = +23.5 (c = 0.36, CHCl 3 ); 96% ee; HPLC analysis AD-H column,n-hexane / iso-propanol=90 / 10,flow rate 1.0mL / min,220nmUV detector,t R (minor)=11.8min,t R (major) = 17.9 min.

[0181] Embodiment 27

[0182]

[0183] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11a, 16.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (42.3 mg, colorless oil, yield 90%) was obtained by column chromatography separation and purification. The target product was measured for rr value (96:4). 1 H NMR (500 MHz, CDCl 3 )δ7.38–7.28(m,5H),5.18–5.07(m,2H),4.84(s,1H),3.29–3.09(m,2H),1.53–1.43(m,2H),1.34–1.23(m,6H),0.88(t,J=7.0Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ156.5,136.8,128.6,128.2,128.1,66.6,41.2,31.5,30.0,26.5,22.6,14.1; HRMS(ESI)calcd.for C 14 H 21 NO 2 Na[M+Na] + m / z 258.1464,found 258.1455;IR(neat,cm -1)3329,2927,2856,1691,1537,1247,1139,734,697.

[0184] Embodiment 28

[0185]

[0186] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL) and stirred at 25 °C for 10 minutes before adding the above olefin (11b, 30.4 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (43.1 mg, colorless oil, yield 71%) was obtained by column chromatography separation and purification. The target product was measured for rr value (97:3). 1 H NMR (400 MHz, CDCl 3 )δ7.38–7.28(m,5H),5.15–5.08(m,2H),4.87(s,1H),3.22–3.14(m,2H),1. 71–1.66(m,4H),1.52–1.45(m,2H),1.31–1.14(m,11H),0.90–0.82(m,2H); 13 C NMR (101 MHz, CDCl 3 )δ156.5,136.8,128.5,128.1,128.1,66.6,41.2,37.6,37.5,33.5,30.0,27.1,26.8,26.6,26.5; HRMS(ESI)calcd.for C 19 H 29 NO 2 Na[M+Na] + m / z326.2090,found 326.2083;IR(neat,cm -1 )3339,2920,2850,1697,1531,1248,1026,733,696.

[0187] Embodiment 29

[0188]

[0189] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11c, 28.0 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (40.5 mg, colorless oil, yield 89%) was obtained by column chromatography separation and purification. The rr value of the target product was measured (96:4). 1 H NMR (500 MHz, CDCl 3 )δ7.40–7.28(m,5H),5.18–5.06(m,2H),4.76(s,1H),3.19(q,J=6.7Hz,2 H),1.54–1.45(m,2H),1.35–1.21(m,6H),1.18–1.11(m,2H),0.86(s,9H); 13 C NMR (126 MHz, CDCl 3 )δ156.5,136.8,128.6,128.2,128.2,66.7,44.3,41.3,30.4,30.4,30.1,29.5,26.9,24.6; HRMS(ESI)calcd.for C 18 H 29 NO 2 Na[M+Na] + m / z 314.2090,found314.2083;IR(neat,cm -1 )3334,2930,2860,1697,1532,1245,1025,734,696.

[0190] Embodiment 30

[0191]

[0192] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL) and stirred at 25 °C for 10 minutes before adding the above olefin (11d, 36.8 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the lid of the reaction tube, and react at 35°C for 24 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (46.9 mg, colorless oil, yield 70%) is separated and purified by column chromatography, and the rr value of the target product is measured (96:4). 1 H NMR (500 MHz, CDCl 3 )δ7.38–7.28(m,5H),5.16–5.07(m,2H),4.83(t,J=4.9Hz,1H),4.77(s,1H),3.99–3.92(m,2H),3.87–3.8 0(m,2H),3.24–3.10(m,2H),1.68–1.60(m,2H),1.52–1.44(m,2H),1.43–1.36(m,2H),1.33–1.24(m,8H); 13 C NMR (126 MHz, CDCl 3 )δ156.5,136.8,128.6,128.2,128.2,104.8,66.7,64.9,41.2,34.0,30.0,29.5,29.5,29.2,26.8,24.1; HRMS(ESI)calcd.forC 19 H 29 NO 4 Na[M+Na] + m / z 358.1989, found 358.1971; IR(neat,cm -1 )3335,2928,2855,1702,1533,1248,1118,1026,737,697.

[0193] Embodiment 31

[0194]

[0195] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL) and stirred at 25 °C for 10 minutes before adding the above olefin (11e, 49.7 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (70.3 mg, white solid, yield 88%) was obtained by column chromatography separation and purification. The target product was measured for rr value (98:2). 1 H NMR (500 MHz, CDCl 3 )δ7.39–7.29(m,5H),5.18–5.06(m,2H),4.71(s,1H),3.22–3.10(m,2H),1.80–1.66(m,8H),1 .56–1.45(m,2H),1.33–1.26(m,2H),1.20–1.08(m,6H),1.03–0.91(m,6H),0.89–0.78(m,7H); 13 C NMR (126 MHz, CDCl 3 )δ156.5,136.8,128.7,128.3,128.2,66.7,43.6,43.5,41.6,40.0,37.8,37.8,34.5,33.8,33.7,30.2,30.1,27.6,20.2,14.6; HRMS(ESI)calcd.forC 26 H 41 NO 2 Na[M+Na] + m / z 422.3029, found 422.3018; mp102.9–103.2℃; IR(neat,cm -1 )3323,2905,2844,1691,1540,1264,1146,1026,731,692.

[0196] Embodiment 32

[0197]

[0198] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL) and stirred at 25 °C for 10 minutes before adding the above olefin (11f, 33.2 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 25°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (44.4 mg, colorless oil, yield 70%) was obtained by column chromatography separation and purification. The target product was measured for rr value (95:5). 1 H NMR (500 MHz, CDCl 3 )δ7.40–7.30(m,5H),7.13–7.09(m,1H),6.93–6.90(m,1H),6.79–6.76(m,1H),5.18–5.08(m,2H),4.76(s ,1H),3.23–3.13(m,2H),2.82(t,J=7.6Hz,2H),1.71–1.63(m,2H),1.55–1.46(m,2H),1.41–1.32(m,4H); 13 C NMR (126 MHz, CDCl 3 )δ156.5,145.6,136.8,128.6,128.2,128.2,126.8,124.1,122.9,66.7,41.1,31.7,30.0,29.9,28.8,26.6; HRMS(ESI)calcd.forC 18 H 23 NNaO 2 S[M+Na] + m / z 340.1342,found 340.1333;IR(neat,cm -1 )3341,2931,2856,1700,1532,1250,1134,1026,736,695.

[0199] Embodiment 33

[0200]

[0201] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11 g, 40.4 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (38.2 mg, white solid, yield 54%) was obtained by column chromatography separation and purification. The target product was measured for rr value (95:5). 1 H NMR (500 MHz, CDCl 3 )δ7.40–7.25(m,7H),7.22–7.15(m,3H),5.19–5.08(m,2H),4.75(s,1H),3.23–3.13( m,2H),2.64–2.59(m,2H),1.66–1.59(m,2H),1.54–1.45(m,2H),1.37–1.23(m,10H); 13 C NMR (126 MHz, CDCl 3 )δ156.5,143.0,136.8,128.6,128.5,128.3,128.2,128.2,125.7,66.7,41.2,36.1,31.6,30.1,29.6,29.5,29.4,29.4,26.8; HRMS(ESI)calcd.for C 23 H 31 NO 2 Na[M+Na] + m / z 376.2247, found 376.2238; mp54.2–55.2℃; IR(neat,cm -1 )3326,2921,2850,1688,1544,1258,1140,1026,746,696.

[0202] Embodiment 34

[0203]

[0204] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL) and stirred at 25 °C for 10 minutes before adding the above olefin (11 h, 42.8, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the lid of the reaction tube, and react at 35°C for 24 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (55.5 mg, colorless oil, yield 76%) is separated and purified by column chromatography, and the rr value of the target product is measured (97:3). 1 H NMR (400 MHz, CDCl 3 )δ7.33–7.19(m,5H),5.07–5.00(m,2H),4.78(s,1H),3.52(t,J=6.5Hz,2H),3.16–3.07(m,2H),1.46–1.24(m,8H),0.83(s,9H),-0.02(s,6H); 13 C NMR (101 MHz, CDCl 3 )δ156.5,136.8,128.6,128.2,128.1,66.6,63.2,41.1,32.8,30.0,26.6,26.1,25.6,18.4,-5.2; HRMS(ESI)calcd.for C 20 H 36 NO 3 Si[M+H] + m / z 366.2459,found 366.2449;IR(neat,cm -1 )3337,2944,2855,1597,1319,1155,813,666,551.

[0205] Embodiment 35

[0206]

[0207] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11i, 34.2, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (27.1 mg, colorless oil, yield 42%) was obtained by column chromatography separation and purification. The target product was measured for rr value (96:4). 1 H NMR (500 MHz, CDCl 3 )δ7.37–7.31(m,5H),5.12–5.07(m,2H),4.82(s,1H),4.55(s,1H),3.24–3.17(m,2H),3.16–3.06(m,2H),1.56–1.48(m,4H),1.44(s,9H); 13 C NMR (126 MHz, CDCl 3 )δ156.6,156.1,136.7,128.7,128.4,128.3,67.1,66.8,40.9,40.3,28.6,27.5,27.4; HRMS(ESI)calcd.forC 17 H 26 N 2 O 4 Na[M+Na] + m / z 345.1785,found 345.1788;IR(neat,cm -1 )3337,2923,2855,1682,1525,1236,1120,1018,695,489.

[0208] Embodiment 36

[0209]

[0210] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (11j, 26.4, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 25°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (40.2 mg, colorless oil, yield 71%) was obtained by column chromatography separation and purification. 1 H NMR (500 MHz, CDCl 3 )δ7.40–7.25(m,7H),7.24–7.06(m,3H),5.19–5.08(m,2H),4.82(s,1H),3.24–3.14(m,1H),3.1 2–2.96(m,1H),2.75–2.63(m,1H),2.44–2.36(m,1H),2.02–1.88(m,1H),0.90(d,J=6.7Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ156.7,140.3,136.7,129.2,128.6,128.4,128.2,126.1,66.8,46.9,41.0,35.8,17.5; HRMS(ESI)calcd.for C 18 H 21 NO 2 Na[M+Na] + m / z306.1464,found 306.1456;IR(neat,cm -1 )3335,2957,1700,1527,1244,1139,1006,740,699.

[0211] Embodiment 37

[0212]

[0213] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (11k, 22.4, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 25°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (39.5 mg, colorless oil, yield 84%) was obtained by column chromatography separation and purification. 1 H NMR (500 MHz, CDCl 3 )δ7.41–7.28(m,5H),5.19–5.05(m,2H),4.91(s,1H),3.25–3.13(m,1H),3.0 5–2.90(m,1H),1.66–1.40(m,2H),0.91(d,J=6.9Hz,3H),0.87–0.77(m,6H); 13 C NMR (126 MHz, CDCl 3 )δ156.6,136.8,128.5,128.1,128.1,66.6,45.2,39.2,29.8,20.5,17.8,13.4; HRMS(ESI)calcd.for C 14 H 21 NO 2 Na[M+Na] + m / z258.1464,found 258.1458;IR(neat,cm -1 )3336,2959,2874,1698,1534,1253,1138,1007,736,697.

[0214] Embodiment 38

[0215]

[0216] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (11 l, 28.4, 0.20 mmol, 1.0 equiv), CbzN 3(2a, 70.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 25°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (31.1 mg, colorless oil, yield 53%) was obtained by column chromatography separation and purification. 1 H NMR (500 MHz, CDCl 3 )δ7.38–7.28(m,5H),5.24–5.07(m,3H),3.41–3.33(m,1H),3.30–3.24(m,1H),2.62–2.53(m,1H),1.43(s,9H),1.14(d,J=7.2Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ174.8,156.6,136.7,128.6,128.2,81.0,66.8,43.6,40.8,28.2,14.9; HRMS(ESI)calcd.for C 16 H 23 NO 4 Na[M+Na] + m / z 316.1519,found316.1512;IR(neat,cm -1 )3353,2977,1724,1523,1368,1248,1153,751,698.

[0217] Embodiment 39

[0218]

[0219] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (49.8 mg, 0.30 mmol, 1.5 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11 m, 16.4, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 53.1 mg, 0.30 mmol, 1.5 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (37.8 mg, white solid, yield 81%) was obtained by column chromatography separation and purification. 1H NMR (500 MHz, CDCl 3 )δ7.39–7.29(m,5H),5.18–5.04(m,2H),4.74–4.58(m,1H),3.57–3.33(m,1H),2.00–1. 88(m,2H),1.73–1.67(m,2H),1.64–1.56(m,1H),1.41–1.28(m,2H),1.21–1.08(m,3H); 13 C NMR (126 MHz, CDCl 3 )δ155.7,136.8,128.6,128.3,128.2,66.6,50.0,33.5,25.6,24.9; HRMS(ESI)calcd.for C 14 H 19 NO 2 Na[M+Na] + m / z 256.1308, found 256.1298; mp89.4–90.4℃; IR(neat,cm -1 )3318,2932,2854,1685,1535,1233,1044,777,693.

[0220] Embodiment 40

[0221]

[0222] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (11a, 16.8, 0.20 mmol, 1.0 equiv), BocN 3 (2b, 57.2 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 25°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (30.2 mg, colorless oil, yield 75%) was obtained by column chromatography separation and purification. The rr value of the target product was measured (>99:1). 1 H NMR (400 MHz, CDCl 3)δ4.54(s,1H),3.12–3.01(m,2H),1.48–1.43(m,2H),1.42(s,9H),1.30–1.23(m,6H),0.89–0.81(m,3H); 13 C NMR (101 MHz, CDCl 3 )δ156.1,79.0,40.7,31.6,30.1,28.5,26.6,22.7,14.1; HRMS(ESI)calcd.for C 11 H 23 NO 2 Na[M+Na] + m / z 224.1621,found 224.1616;IR(neat,cm -1 )3344,2963,1686,1529,1365,1247,1171,754.

[0223] Embodiment 41

[0224]

[0225] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (11a, 16.8, 0.20 mmol, 1.0 equiv), N 3 CO 2 Et (2c, 46 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the lid of the reaction tube, and react at 25°C for 24 hours. After the reaction is completed, the reaction solvent is removed by concentration under reduced pressure, and the target product (25.6 mg, colorless oil, yield 74%) is separated and purified by column chromatography, and the rr value of the target product is measured (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ4.66(s,1H),4.16–4.05(m,2H),3.19–3.07(m,2H),1.51–1.43(m,2H),1.31–1.20(m,9H),0.90–0.84(m,3H); 13 C NMR (126 MHz, CDCl 3)δ156.8,60.7,41.1,31.6,30.1,26.5,22.7,14.8,14.1; HRMS(ESI)calcd.for C 9 H 20 NO 2 [M+H] + m / z 174.1489,found 174.1486;IR(neat,cm -1 )3335,2930,2859,1697,1537,1251,1046,779.

[0226] Embodiment 42

[0227]

[0228] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11a, 16.8 mg, 0.20 mmol, 1.0 equiv), FmocN 3 (2d, 106 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (54.9 mg, white solid, yield 85%) was obtained by column chromatography separation and purification. The target product was measured for rr value (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ7.77(d,J=7.5Hz,2H),7.60(d,J=7.5Hz,2H),7.44–7.37(m,2H),7.35–7.28(m,2H),4.74(s,1H ),4.47–4.36(m,2H),4.30–4.18(m,1H),3.25–3.05(m,2H),1.54–1.24(m,8H),0.94–0.86(m,3H); 13 C NMR (126 MHz, CDCl 3)δ156.5,144.2,141.5,127.8,127.1,125.2,120.1,66.6,47.5,41.2,31.6,30.1,26.5,22.7,14.2; HRMS(ESI)calcd.for C 21 H 25 NO 2 Na[M+Na] + m / z 346.1777, found 346.1768; mp111.5–112.8℃; IR(neat,cm -1 )3334,2923,2854,1689,1542,1446,1262,1144,737,645.

[0229] Embodiment 43

[0230]

[0231] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in dry chloroform (1.0 mL), stirred at 25 °C for 10 minutes, and then the above olefin (11a, 16.8 mg, 0.20 mmol, 1.0 equiv), TrocN 3 (2e, 86.8 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 35°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (40.2 mg, colorless oil, yield 73%) was obtained by column chromatography separation and purification, and the rr value of the target product was measured (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ4.96(s,1H),4.77–4.68(m,2H),3.27–3.19(m,2H),1.58–1.49(m,2H),1.37–1.27(m,6H),0.93–0.86(m,3H); 13 C NMR (126 MHz, CDCl 3 )δ154.7,95.8,74.6,41.5,31.5,29.9,26.5,22.7,14.1; HRMS(ESI)calcd.for C 9 H 17 Cl3 NO 2 [M+H] + m / z 276.0320,found 276.0314;IR(neat,cm -1 )3337,2927,2856,1713,1542,1245,1146,817,724,568.

[0232] Embodiment 44

[0233]

[0234] Under nitrogen atmosphere, nickel iodide (5.0 mg, 8 mol%) and ligand (±)-L7 (6.3 mg, 10 mol%) were added to the reaction tube and dissolved in 1.0 mL of dry chloroform. After stirring at 25 °C for 10 minutes, the above olefin (11a, 16.8 mg, 0.20 mmol, 1.0 equiv) and TsN were added. 3 (2f, 57.6 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv), cover the reaction tube, and react at 50°C for 24 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (41.8 mg, white solid, yield 82%) was obtained by column chromatography separation and purification. The target product was measured for rr value (96:4). 1 H NMR (400 MHz, CDCl 3 )δ7.77–7.73(m,2H),7.32–7.27(m,2H),4.85–4.70(m,1H),2.90(q,J=6.8Hz, 2H),2.41(s,3H),1.47–1.38(m,2H),1.26–1.15(m,6H),0.82(t,J=6.9Hz,3H); 13 C NMR (101 MHz, CDCl 3 )δ143.3,137.0,129.7,127.1,43.2,31.2,29.5,26.2,22.4,21.5,13.9; HRMS(ESI)calcd.for C 13 H 21 NNaO 2 S[M+Na] + m / z 278.1185, found278.1177; mp62.7–63.5℃; IR(neat,cm -1 )3280,2923,2855,1597,1419,1319,1155,812,666,551.

[0235] Embodiment 45

[0236]

[0237] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran, stirred at 25°C for 10 minutes, and then the above olefin (11a, 16.8, 0.20 mmol, 1.0 equiv), DPPA (2 g, 110 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv) were added, the lid of the reaction tube was covered, and the reaction was carried out at 35°C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and the target product (54.6 mg, colorless oil, yield 82%) was obtained by column chromatography separation and purification, and the rr value of the target product was measured (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ7.35–7.29(m,4H),7.29–7.24(m,4H),7.19–7.11(m,2H),3.55–3.40(m,1H) ,3.08–3.01(m,2H),1.47–1.40(m,2H),1.28–1.19(m,6H),0.89–0.83(m,3H); 31 P NMR (202 MHz, CDCl 3 )δ-0.42; 13 C NMR (126 MHz, CDCl 3 )δ151.0(d,J=6.3Hz),129.7,124.9,120.3(d,J=5.0Hz),41.9(d,J=1.3Hz),31.4(d,J=6.3Hz),31.4,26.2,22.6,14.1; HRMS(ESI)calcd.forC 18 H 25 NO 3 P[M+H] + m / z 334.1567,found 334.1556;IR(neat,cm -1 )3220,2929,2858,1591,1489,1191,922,758,688,503.

[0238] Embodiment 46

[0239]

[0240] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran, stirred at 25°C for 10 minutes, and then the above olefin (11c, 28.0, 0.20 mmol, 1.0 equiv), DPPA (2 g, 110 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv) were added, the lid of the reaction tube was covered, and the reaction was carried out at 35°C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and the target product (52.9 mg, colorless oil, yield 68%) was obtained by column chromatography separation and purification, and the rr value of the target product was measured (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ7.35–7.30(m,4H),7.28–7.25(m,4H),7.18–7.14(m,2H),3.27–3.18(m, 1H),3.10–3.02(m,2H),1.48–1.42(m,2H),1.28–1.11(m,8H),0.85(s,9H); 31 P NMR (202 MHz, CDCl 3 )δ-0.55; 13 CNMR (126MHz, CDCl 3 )δ151.0(d,J=6.3Hz),129.8,125.0,120.3(d,J=5.0Hz),44.2,41.9(d,J=1.3Hz),31.6(d,J=6.3Hz),30.4,30.2,29.5,26.7,24.5; HRMS(ESI)calcd.forC 22 H 33 NO 3 P[M+H] + m / z 390.2193,found 390.2181;IR(neat,cm -1 )3226,2931,2861,1592,1195,928,767,689.

[0241] Embodiment 47

[0242]

[0243] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran, stirred at 25°C for 10 minutes, and then the above olefin (11n, 16.8, 0.20 mmol, 1.0 equiv), DPPA (2 g, 110 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv) were added, the lid of the reaction tube was covered, and the reaction was carried out at 35°C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and the target product (56.0 mg, colorless oil, yield 84%) was obtained by column chromatography separation and purification, and the rr value of the target product was measured (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ7.36–7.30(m,4H),7.28–7.24(m,4H),7.18–7.13(m,2H),3.52–3.41(m,1H) ,3.08–3.01(m,2H),1.49–1.41(m,2H),1.29–1.19(m,6H),0.88–0.83(m,3H); 31 P NMR (202 MHz, CDCl 3 )δ-0.42; 13 C NMR (126 MHz, CDCl 3 )δ151.0(d,J=6.3Hz),129.7,124.9,120.3(d,J=5.0Hz),41.9(d,J=1.3Hz),31.4(d,J=6.3Hz),31.4,26.2,22.6,14.1; HRMS(ESI)calcd.forC 18 H 25 NO 3 P[M+H] + m / z 334.1567,found 334.1557;IR(neat,cm -1 )3220,2929,2858,1591,1489,1191,922,758,688,503.

[0244] Embodiment 48

[0245]

[0246] Under nitrogen atmosphere, nickel iodide (3.2 mg, 5 mol%), ligand (±)-L7 (5.0 mg, 8 mol%), and potassium iodide (66.4 mg, 0.40 mmol, 2.0 equiv) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran, stirred at 25°C for 10 minutes, and then the above olefin (11o, 39.6, 0.20 mmol, 1.0 equiv), DPPA (2 g, 110 mg, 0.40 mmol, 2.0 equiv) and pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv) were added, the lid of the reaction tube was covered, and the reaction was carried out at 35°C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and the target product (55.5 mg, colorless oil, yield 62%) was obtained by column chromatography separation and purification, and the rr value of the target product was measured (>99:1). 1 H NMR (500 MHz, CDCl 3 )δ7.34–7.30(m,4H),7.26–7.23(m,4H),7.17–7.13(m,2H),4.04(t,J=6.8Hz,2H),3.25–3.18(m ,1H),3.08–3.02(m,2H),2.03(s,3H),1.64–1.57(m,2H),1.47–1.41(m,2H),1.34–1.21(m,12H); 31 P NMR (202 MHz, CDCl 3 )δ-0.55; 13 C NMR (126 MHz, CDCl 3 )δ171.3,151.0(d,J=7.6Hz),129.7,124.9,120.3(d,J=5.0Hz),64.7,41.9(d,J=1.3Hz) ,31.5(d,J=6.3Hz),29.5,29.5,29.3,29.2,28.7,26.6,26.0,21.1; HRMS(ESI)calcd.for C 24 H 35 NO 5 P[M+H] + m / z448.2248,found 448.2231;IR(neat,cm -1 )3226,2927,2855,1737,1591,1239,1194,767,690.

[0247] Embodiment 49

[0248]

[0249] Under nitrogen atmosphere, nickel iodide (5 mg, 8 mol%) and ligand (S,S)-L7 (6.3 mg, 10 mol%) were added to the reaction tube. Molecular sieves (20 mg) were dissolved in 1.0 mL of dry tetrahydrofuran and stirred at 25 °C for 10 minutes before adding the above olefin (11w, 20 mg, 0.20 mmol, 1.0 equiv), CbzN 3 (2a, 70.8 mg, 0.40 mmol, 2.0 equiv), pinacol borane (51.2 mg, 0.40 mmol, 2.0 equiv) and trimethylsilyl chloride (15.3 mg, 0.14 mmol, 0.7 equiv), cover the reaction tube, and react at 0°C for 36 hours. After the reaction, the reaction solvent was removed by concentration under reduced pressure, and the target product (30.6 mg, colorless oil, yield 61%) was obtained by column chromatography separation and purification. 1 H NMR (500 MHz, CDCl 3 )δ7.39–7.28(m,5H),5.20(s,1H),5.09(s,2H),3.68(s,3H),3.44–3.28(m,2H),2.76–2.65(m,1H),1.18(d,J=7.2Hz,3H); 13 C NMR (126 MHz, CDCl 3 )δ175.8,156.6,136.6,128.7,128.3,128.2,66.9,52.0,43.5,40.0,14.9; HRMS(ESI)calcd.for C 13 H 17 NNaO 4 [M+Na] + m / z 274.1050,found 274.1049;IR(neat,cm -1 )3364,2950,1733,1700,1523,1241,1007,699;[α] D 31 = +19.4 (c = 0.41, CHCl 3 ); 87% ee; HPLC analysis OB-H column,n-hexane / iso-propanol=95 / 5,flowrate 1.0mL / min,220nm UV detector,t R (major)=30.1min,t R (minor)=38.1min.

Claims

1. A method for the asymmetric hydroamination of olefins by nickel catalysis, characterized in that: The following steps are involved: In an inert gas, a metal nickel catalyst, an achiral ligand L or a chiral ligand L*, a hydrogen source, and an additive are dissolved in an organic solvent, and then an aromatic olefin is added. Aryl substituted remote olefins Olefins containing carbonyl directing groups Alkyl Olefins or α-acrylate substituted olefin and an azidoamine compound N3–PG as an amine source, PG being a carbonate protecting group, p-toluenesulfonyl or diphenylphosphonic acid group, to obtain a reaction mixture, which is then post-treated and purified to obtain the target: Enantiomerically enriched α-aryl substituted chiral amine products or its enantiomer Migration of chiral amine products or its enantiomer Migration of chiral amine products containing carbonyl directing groups or its enantiomer or its enantiomer Alkylamine compounds In situ chiral amine products containing α-substituted acrylates or its enantiomer Among them, R 1 , R 2 is a terminal substituent of an olefin, which is any one of a hydrogen atom, an alkyl group, an aryl group, an ester group, an amide group, an amine group, a protected amine group, and a silyl ether; R 3 , R 4 , R 5 , R 6 and R 7 The structure is one of aryl (Aryl), alkyl (Alkyl) or hydrogen atom (H); When Ar is an aryl group, the substituent on the aryl group is any one of a chlorine atom, a (hetero)aryl group, a (fluorinated) alkyl group, a (thio) ether, a ketone, an aldehyde, an ester, an amide, and a cyano group; when Ar is a heteroaryl group, it is any one of pyridine and pyrimidine, and the substituent on the heteroaryl group is any one of a chlorine atom, a fluorine atom, a (fluorinated) alkyl group, and an alkoxy group; The achiral ligand L is any one of the following: The chiral ligand L* is any one of the following: The solvent is one or more of ethyl acetate, acetonitrile, ether, ethanol, acetone, toluene, ethylbenzene, trifluorotoluene, mesitylene, N-methylpyrrolidone, ethylene glycol dimethyl ether, dichloromethane, dichloroethane, chloroform, tetrahydrofuran, 1,4-dioxane, and 1,3-dioxolane; The nickel-catalyzed asymmetric hydroamination of olefins can be prepared by any of the following routes: Preparation route 1: Preparation route 2: Preparation route 3: Preparation route 4: Preparation route 5: Preparation route 6:

2. The method for asymmetric hydroamination of olefins by nickel catalysis according to claim 1, characterized in that: The metal nickel catalyst is metal nickel salt, hydrogen source borohydride pinacol borane, the additive is inorganic salt of iodine, phosphine salt or lithium salt, and the organic solvent is tetrahydrofuran, toluene or dichloromethane.

3. The method for asymmetric hydroamination of olefins catalyzed by nickel according to claim 1, characterized in that: The nickel-catalyzed asymmetric hydroamination of olefins can be prepared by any of the following routes: Preparation route 1: The molar ratio of olefin 1 to amine source 2 in route 1 is 2.5:1, NiBr2·DME is a nickel catalyst nickel bromide (II)·ethylene glycol dimethyl ether, and the chiral ligand L1* is or its enantiomer HBpin is the hydrogen source pinacol borane, PCy3 is the additive tricyclohexylphosphine, LiI is the additive, Molecular sieve is used as dehydrating agent and toluene is used as solvent; Preparation route 2: The molar ratio of olefin 5 and amine source 2 in route 2 is 2:1, Ni(ClO4)2·6H2O is nickel catalyst nickel perchlorate (II) hexahydrate, and the chiral ligand L5* is or its enantiomer HBpin is the hydrogen source pinacol borane, LiPF6 is the additive lithium hexafluorophosphate, Molecular sieves are water removal agents, and THF is tetrahydrofuran solvent; Preparation route 3: The molar ratio of olefin 7 and amine source 2 in route 3 is 2:1, NiCl2·(PCy 3)2 The nickel catalyst is bis(tricyclohexylphosphine)nickel dichloride, and the ligand L6* is or its enantiomer HBpin is the hydrogen source pinacol borane, THF is the solvent tetrahydrofuran; Preparation route 4: The molar ratio of olefin 9 and amine source 2 in route 4 is 2:1, NiCl2·(PCy 3)2 The nickel catalyst is bis(tricyclohexylphosphine)nickel dichloride, and the ligand L6* is or its enantiomer HBpin is the hydrogen source pinacol borane, THF is the solvent tetrahydrofuran; Preparation route 5: The molar ratio of olefin 11 and amine source 2 in route 5 is 2:1, NiI2 is nickel catalyst nickel iodide, and ligand (±)L7 is HBpin is the hydrogen source pinacol borane, KI is the additive potassium iodide, Molecular sieve is the dehydrating agent, CHCl3 is the solvent chloroform; Preparation route 6: The molar ratio of olefin 13 and amine source 2 in route 6 is 2:1, NiI2 is a nickel catalyst nickel iodide, and the ligand (S,S)-L7* is HBpin is the hydrogen source pinacol borane, KI is the additive potassium iodide, MS molecular sieve as water removal agent molecular sieves, CHCl3 as solvent and chloroform.

4. The method for asymmetric hydroamination of olefins catalyzed by nickel according to claim 1, characterized in that: The azide compound N3-PG is any one of CbzN3, BocN3, CO2EtN3, TrocN3, DPPA, FmocN3, and TsN3.

5. The method for asymmetric hydroamination of olefins catalyzed by nickel according to claim 1, characterized in that: The nickel-catalyzed asymmetric hydrogenation method of olefins described in route 1, at -10°C to 50°C and in a solvent, in the presence of a metal nickel catalyst, a chiral ligand L*, a hydrogen source, an additive, and a molecular sieve, the olefin and the amine source react for 1 hour to 48 hours; the molar ratio of the metal nickel catalyst, the chiral ligand L*, the hydrogen source, the additive, the molecular sieve, the olefin and the amine source is (0.001-0.20): (0.001-0.30): (1.0-6.0): (0.01-3.0): (1.0-4.0): (1.0-4.0): (1.0-4.0): (1.0-4.0); The nickel-catalyzed selective distal asymmetric hydrogenation method of olefins described in route 2 is to react olefins and amine sources for 1 hour to 48 hours in a solvent at -10°C to 50°C in the presence of a metal nickel catalyst, a chiral ligand L*, a hydrogen source, an additive, and a molecular sieve; the molar ratio of the metal nickel catalyst, the chiral ligand L*, the hydrogen source, the additive, the molecular sieve, the olefin, and the amine source is (0.001-0.20): (0.001-0.30): (1.0-6.0): (0.01-3.0): (1.0-4.0): (1.0-4.0): (1.0-4.0): (1.0-4.0); The nickel-catalyzed migratory asymmetric hydrogenation reaction of olefinic amides described in route 3 is carried out at -10°C to 50°C in a solvent in the presence of a metal nickel catalyst, a chiral ligand L*, a hydrogen source, an additive, and a molecular sieve, and the olefin and the amine source are reacted for 1 hour to 48 hours; the molar ratio of the metal nickel catalyst, the chiral ligand L*, the hydrogen source, the additive, the molecular sieve, the olefin and the amine source is (0.001-0.20): (0.001-0.30): (1.0-6.0): (0.01-3.0): (1.0-4.0): (1.0-4.0): (1.0-4.0): (1.0-4.0); The nickel-nickel-catalyzed migratory asymmetric hydrogenation reaction of olefinic amides described in route 4 is carried out at -10°C to 50°C in a solvent in the presence of a metal nickel catalyst, a chiral ligand L*, a hydrogen source, an additive, and a molecular sieve, and the olefin and the amine source are reacted for 1 hour to 48 hours; the molar ratio of the metal nickel catalyst, the chiral ligand L*, the hydrogen source, the additive, the molecular sieve, the olefin and the amine source is (0.001-0.20):(0.001-0.30):(1.0-6.0):(0.01-3.0):(1.0-4.0):(1.0-4.0):(1.0-4.0):(1.0-4.0); The nickel-catalyzed migratory hydrogen aromatic amination method of olefins described in route 5 comprises reacting olefins and amine sources for 1 hour to 48 hours in a solvent at -10°C to 50°C in the presence of a metal nickel catalyst, a ligand (±)L, a hydrogen source, an additive, and a molecular sieve; the molar ratio of the metal nickel catalyst, the ligand (±)L, the hydrogen source, the additive, the molecular sieve, the olefin, and the amine source is (0.001-0.20):(0.001-0.30):(1.0-6.0):(0.01-3.0):(1.0-4.0):(1.0-4.0):(1.0-4.0):(1.0-4.0); The nickel-catalyzed asymmetric hydroarylation method of olefins described in route 6 comprises reacting olefins and amine sources for 1 hour to 48 hours in a solvent at -10°C to 50°C in the presence of a metal nickel catalyst, a ligand L*, a hydrogen source, an additive, and a molecular sieve; the molar ratio of the metal nickel catalyst, the chiral ligand L*, the hydrogen source, the additive, the molecular sieve, the olefin, and the amine source is (0.001-0.20):(0.001-0.30):(1.0-6.0):(0.01-3.0):(1.0-4.0):(1.0-4.0):(1.0-4.0):(1.0-4.0).

6. The method for asymmetric hydroamination of olefins catalyzed by nickel according to claim 1, characterized in that: The metal nickel salt is any one of nickel chloride, nickel chloride hexahydrate, nickel chloride ethylene glycol dimethyl ether complex, nickel bromide, nickel bromide trihydrate, nickel bromide diethylene glycol dimethyl ether complex, nickel bromide ethylene glycol dimethyl ether complex, nickel iodide, nickel iodide hexahydrate, bis-(1,5-cyclooctadiene) nickel complex, nickel nitrate hexahydrate, nickel perchlorate hexahydrate, and nickel tetrafluoroborate hexahydrate; The hydrogen source is borohydride pinacol borane; The additive is one or more of lithium chloride, sodium chloride, lithium bromide, potassium bromide, magnesium bromide, magnesium bromide hydrate, lithium iodide, sodium iodide, zinc iodide, magnesium iodide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, sodium acetate, potassium acetate, methanol, isopropanol, tert-butanol, hexafluoroisopropanol, benzyl alcohol, acetonitrile, tricyclohexylphosphine, triphenylphosphine, and lithium hexafluorophosphate; The solvent is one or more of tetrahydrofuran, 1,4-dioxane, toluene, dichloromethane, chloroform, and N-methylpyrrolidone.

7. The method for asymmetric hydroamination of olefins catalyzed by nickel according to claim 1, characterized in that: The specific preparation method reaction route is as follows:

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