CN113754689A - 一种镍催化的烯烃不对称氢胺化方法 - Google Patents

一种镍催化的烯烃不对称氢胺化方法 Download PDF

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CN113754689A
CN113754689A CN202110888015.6A CN202110888015A CN113754689A CN 113754689 A CN113754689 A CN 113754689A CN 202110888015 A CN202110888015 A CN 202110888015A CN 113754689 A CN113754689 A CN 113754689A
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朱少林
孟令普
杨竞捷
段美
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Abstract

本发明公开了使用一种镍和配体组合催化实现对烯烃的不对称氢芳胺化、氢烷基胺化以及氢酰胺化，属于有机化学和药物化学领域。本发明在金属镍源、手性配体、氢源、添加剂等作用下，使烯烃与不同的胺源在有机溶剂中进行反应，以优异的对映选择性和良好的收率得到系列手性胺化合物。本发明使用廉价的过渡金属镍作为催化剂，使用简单易得的烯烃和胺源作为原料，条件温和简单，官能团兼容性良好，操作简便。

Description

一种镍催化的烯烃不对称氢胺化方法
技术领域
本发明方法属于有机化学和药物化学领域，使用镍和手性Biox配体组合催化实现烯烃的不对称氢芳胺化、氢烷基胺化以及氢酰胺化，得到三类重要的α-手性苄胺类中间体，适用面非常广泛。
背景技术
在过去的二十年里，廉价金属氢催化如FeH、CoH和CuH开始受到合成化学家们的关注。镍廉价易得，具有多样性的氧化态，在偶联化学领域具有独特而广泛的应用，相应的NiH催化能实现来源易得烯烃的多样性、高附加值的转化，得到系列高附加值的产物。
手性胺以及衍生物在医药、农药和材料化学等领域中方面有着广泛的应用，是我们生活中不可或缺的一类化合物。烯烃来源广泛、易制备，被广泛地用于各种有机合成中。近年来，从烯烃出发，利用金属氢催化的烯烃氢官能团化策略能快速地向分子中引入一系列的官能团，其中烯烃的催化不对称氢胺化是制备手性胺最简洁高效的方法之一。已报道的金属氢催化的不对称氢胺化主要有以下几条：
2013年，Buchwald课题组(S.Zhu,N.Niljianskul,S.L.Buchwald,J.Am.Chem.Soc.2013,135,15746.)和Miura课题组(Y.Miki,K.Hirano,T.Satoh,M.Miura,Angew.Chem.Int.Ed.2013,52,10830.)分别使用铜盐/手性膦配体组合实现了铜氢催化的芳基取代烯烃的不对称氢烷基胺化制备手性烷基胺。
Figure BDA0003194919090000011
Figure BDA0003194919090000012
2018年，Buchwald课题组使用铜盐/手性膦配体组合实现了铜氢催化的芳基取代烯烃的不对称氢芳基胺化制备手性芳基胺(S.Ichikawa,S.Zhu,S.L.Buchwald,Angew.Chem.Int.Ed.2018,57,8714.)。
Figure BDA0003194919090000021
紧接着2018年，Buchwald课题组(Y.Zhou,O.D.Engl,J.S.Bandar,E.D.Chant,S.L.Buchwald,Angew.Chem.Int.Ed.2018,57,6672.)使用铜盐/手性膦配体组合实现了铜氢催化的简单芳基取代烯烃的不对称氢酰基胺化制备手性酰胺，其中烯烃底物局限于β-位没有取代的芳基烯烃。
Figure BDA0003194919090000022
虽然上述铜氢催化的氢胺化策略可以实现特定的α-手性苄胺类产物，包括手性烷基胺、手性芳基胺、手性酰胺的制备，但是缺点是需要使用到结构复杂、合成步骤长、价格较高手性膦配体。
南京大学朱少林课题组长期致力于镍氢催化化学，实现了系列烯烃的(迁移)不对称氢官能团化，选择性引入芳基、烷基等官能团，进一步通过手性配体可以调控反应的对映选择性。本发明发展的镍氢催化的不对称氢胺化合成手性胺的方法只需要使用到结构简单、容易合成的N,N-Biox配体；同时更为廉价易得的硝基芳烃也可以作为胺源。而且简单的N,N-Biox配体可以分别实现了烯烃的不对称氢芳基胺化、不对称氢烷基化、不对称氢酰胺化，底物适用范围广，我们这一发明为手性胺的合成提供了一种全新且高效的方法。
发明内容
本发明的目的是提供新颖的手性胺化合物的合成方法，该方法原料廉价易得，操作简便，底物范围广且官能团兼容性好，具有优异的对映选择性和良好的收率。
本发明实现上述目的之一采用以下技术方案：一种镍催化烯烃的不对称氢胺化方法，包括以下步骤：在惰性气体中，将金属镍类催化剂、手性配体L*、氢源、添加剂溶于有机溶剂中，然后加入烯烃
Figure BDA0003194919090000023
和胺源Ar-NO2、R2R3NOBz，
Figure BDA0003194919090000024
中的一种，得到反应混合物，后处理纯化得到目标产物(
Figure BDA0003194919090000025
或其对映体
Figure BDA0003194919090000026
)；
其中，R1为烯烃的末端取代基，为氢原子、烷基、芳基、酯基、酰胺、胺基、保护的胺基、硅醚中的任一种；
R2结构为芳基(Aryl)、烷基(Alkyl)或氢原子(H)中的一种；
R3结构为芳基(Aryl)、烷基(Alkyl)或氢原子(H)中的一种；
Ar为取代芳基或杂芳基；
所述的手性配体L*为Biox配体，结构式为：
Figure BDA0003194919090000031
或其对映体
Figure BDA0003194919090000032
优选的，制备路线1：
Figure BDA0003194919090000033
路线1中的Ni(BF4)2·6H2O为镍类催化剂四氟硼酸镍(II)六水合物，手性配体L*为
Figure BDA0003194919090000034
或其对映体
Figure BDA0003194919090000035
(MeO)3SiH为氢源三甲氧基硅烷，NaI为添加剂碘化钠，Zn为还原剂锌粉，AlF3为碱三氟化铝，toluene为溶剂甲苯；
制备路线2：
Figure BDA0003194919090000036
路线2中的NiCl2·6H2O为镍类催化剂氯化镍(II)六水合物，手性配体L*为
Figure BDA0003194919090000037
或其对映体
Figure BDA0003194919090000038
(MeO)3SiH为氢源三甲氧基硅烷，NaI为添加剂碘化钠，THF为溶剂为四氢呋喃；
制备路线3：
Figure BDA0003194919090000039
路线3中的NiCl2·6H2O为镍类催化剂氯化镍(II)六水合物，手性配体L*为
Figure BDA00031949190900000310
或其对映体
Figure BDA00031949190900000311
(MeO)3SiH为氢源三甲氧基硅烷，NaI为添加剂1碘化钠，CH3OH为添加剂2甲醇，1,4-dioxane/THF为溶剂1,4-二氧六环/四氢呋喃。
优选的，所述Ar中芳基上的取代基为氢原子、氟原子、氯原子、溴原子、烷氧基、含氟烷基、硫醚、酚羟基、酮、醛、酯基、胺基、保护的胺基、酰胺、芳环、杂芳基的任一种；杂芳基为吡啶、呋喃、噻吩、吡唑、吲哚中的任一种。
优选的，所述金属镍类催化剂是金属镍盐、氢源是硅氢或硼氢频哪醇硼烷或硼烷二甲硫醚、添加剂是碘的无机盐。
优选的，路线1所述的镍催化烯烃的不对称氢芳胺化方法，在–10℃～40℃下和溶剂中，在金属镍类催化剂、手性配体L*、氢源、添加剂、还原剂、碱存在的条件下，烯烃和胺源反应1小时～48小时；所述的金属镍类催化剂、手性配体L*、氢源、添加剂、还原剂、碱、烯烃和胺源的摩尔比是(0–0.20)：(0–0.30)：(1.0–6.0)：(0–3.0)：(1.0–4.0)：(1.0–4.0)：(1.0–4.0)：(1.0–4.0)；所述的反应时间以检测反应完全为止。
优选的，路线2所述的镍催化烯烃的不对称氢烷基胺化方法，在–10℃～40℃下和溶剂中，在金属镍类催化剂、手性配体L*、氢源、添加剂存在的条件下，烯烃和胺源反应1小时～48小时；所述的金属镍类催化剂、手性配体L*、氢源、添加剂、烯烃和胺源的摩尔比是(0–0.20)：(0–0.30)：(1.0–6.0)：(0–3.0)：(1.0–4.0)：(1.0–4.0)；所述的反应时间以检测反应完全为止。
优选的，路线3所述的镍催化烯烃的不对称氢酰胺化方法，在–10℃～40℃下和溶剂中，在金属镍类催化剂、手性配体L*、氢源、添加剂1和添加剂2存在的条件下，烯烃和胺源反应1小时～48小时；所述的金属镍类催化剂、手性配体L*、氢源、添加剂1、添加剂2、烯烃和胺源的摩尔比是(0–0.20)：(0–0.30)：(1.0–4.0)：(0–3.0)：(0–4.0)：(1.0–4.0)；所述的反应时间以检测反应完全为止。
优选的，所述的金属镍盐是氯化镍、氯化镍六水合物、氯化镍乙二醇二甲醚复合物、溴化镍、溴化镍三水合物、溴化镍二乙二醇二甲醚复合物、溴化镍乙二醇二甲醚复合物、双-(1,5-环辛二烯)镍复合物、硝酸镍六水合物、高氯酸镍六水合物、四氟硼酸镍六水合物中的任一种；
所述的氢源为聚甲基氢硅氧烷(PMHS)、三甲氧基硅烷、三乙氧基硅烷、二乙氧基甲基硅烷(DEMS)、苯基硅烷、二苯基硅烷、三苯基硅烷、三乙基硅烷、硼烷二甲硫醚、频哪醇硼烷中的任一种；
所述的添加剂为氯化锂、氯化钠、溴化锂、溴化钾、溴化镁、溴化镁水合物、碘化锂、碘化钠、碘化锌、碘化镁、四丁基氯化铵、四丁基溴化铵、四丁基碘化铵、乙酸钠、乙酸钾、甲醇、异丙醇、叔丁醇、六氟异丙醇、苄醇、乙腈中的一种或多种；
所述的溶剂为四氢呋喃、1,4-二氧六环、乙二醇二甲醚、二乙二醇二乙醚、甲苯、二甲苯、三甲苯、三氟甲苯、1,2-二氯乙烷、氯仿、乙腈、N,N-二甲基乙酰胺、N,N-二甲基甲酰胺、N,N-二甲基丙烯基脲、N-甲基吡咯烷酮、二甲基亚砜、甲醇、乙醇和水中的一种或多种。
优选的，胺源为Ar-NO2反应中还需增加碱，其阳离子为Li+、Na+、K+、Cs+、Mg2+和Al3+中的任一种，阴离子为[CO3]2-、[HCO3]-、[PO4]3-、[HPO4]2-、[H2PO4]-、F-、[OH]-、[CH3COO]-、[OMe]-和[OtBu]-中的任一种。
优选的，所述的烯烃为反式构型的烯烃，结构式如下：
Figure BDA0003194919090000041
有益效果：
1、所述的反应温度为–10℃～40℃，反应条件温和，反应效果良好，能以有优异的收率和对映选择性得到产物。
2、所述的胺源之一为硝基芳烃，这一原料是工业上最基本的芳胺初级原料，我们这一发明成为了第一个以硝基芳烃作为胺源实现不对称胺化。
3、所述的镍催化烯烃的不对称胺化可以通过一种配体同时实现不对称芳胺化、不对称烷基胺化以及不对称酰胺化，适用面广泛。
4、所述的手性配体L*的作用：与金属镍配位，在反应的过程中控制手性，并且镍氢加成到烯烃上的过程不可逆，一旦镍氢加成到烯烃上不会进一步发生β-H消除或者均裂反应。
5、烯烃可以为反式、顺式以及顺反异构，但烯烃为纯反式时，得到的目标产物的对映选择性最优。我们这一发明通过实施例7和实施例8可以看出不同的烯烃的构型反应效果有较大的差异，反式构型的烯烃相比顺式构型的烯烃具有更优异的对映选择性。
6、条件中的手性配体L*与其他手性配体相比，具有更好的收率、更优异的对映选择性。
附图说明
下面结合附图对本发明的作进一步说明。
图1是实例1产物的H谱；
图2是实例1产物的C谱；
图3是实例5产物的H谱；
图4是实例5产物的C谱；
图5是实例13产物的H谱；
图6是实例13产物的C谱；
图7是实例30产物的H谱；
图8是实例30产物的C谱；
图9是实例37产物的H谱；
图10是实例37产物的C谱；
图11是实例49产物的H谱；
图12是实例49产物的C谱；
图13是实例57产物的H谱；
图14是实例57产物的C谱；
图15是实例58产物的H谱；
图16是实例58产物的C谱；
图17是实例60产物的H谱；
图18是实例60产物的C谱。
具体实施方式
通过以下详细说明可以进一步理解本发明的特点和优点。所提供的实施例仅是对本发明方法的说明，而不以任何方式限制本发明揭示的其余内容。
下述实施例中，TBS指
Figure BDA0003194919090000051
NiCl2·6H2O指六水氯化镍，Ni(BF4)2·6H2O指六水四氟硼酸镍，(MeO)3SiH指三甲氧基硅烷，toluene指甲苯，c-hexane指环己烷，1,4-dioxane指1,4二氧六环，L*配体为
Figure BDA0003194919090000052
THF指四氢呋喃，equiv指当量数。
实施例1
Figure BDA0003194919090000053
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv)，氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(38.8mg，黄色油状，产率76％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.28–7.26(m,1H),7.26–7.24(m,1H),6.91(d,J＝8.3Hz,2H),6.88–6.84(m,2H),6.48(d,J＝8.4Hz,2H),4.16(t,J＝6.7Hz,1H),3.79(s,3H),2.20(s,3H),1.92–1.73(m,2H),0.94(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.6,145.0,135.9,129.7,127.7,126.7,114.0,113.9,59.9,55.3,31.6,20.5,10.9；HRMS(ESI)calcd.for C17H21NNaO[M+Na]+m/z 278.1515,found 278.1514；IR(neat,cm-1)2923,1613,1510,1243,1033,805；[α]D 26＝–30.7(c＝1.2,CHCl3)；HPLC analysis CHIRALCELOJ-H column,15％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝17.8min,tR(major)＝21.2min。
实施例2
Figure BDA0003194919090000061
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(59.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(34.7mg,黄色油状，产率68％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.26–7.20(m,1H),6.96–6.86(m,4H),6.79–6.73(m,1H),6.51–6.43(m,2H),4.17(t,J＝6.7Hz,1H),3.79(s,3H),2.19(s,3H),1.91–1.75(m,2H),0.96(t,J＝8.0Hz,3H)；13C NMR(126MHz,CDCl3)δ156.0,145.9,145.1,129.7,129.6,126.7,119.1,113.7,112.5,112.1,60.4,55.3,31.6,20.5,11.0；HRMS(ESI)calcd.for C17H21NNaO[M+Na]+m/z 278.1515,found 278.1512；IR(neat,cm-1)2962,1518,1258,1043,804,699；[α]D 26＝–22.0(c＝1.1,CHCl3)；HPLC analysis CHIRALCEL OJ-Hcolumn,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝24.7min,tR(major)＝33.8min。
实施例3
Figure BDA0003194919090000062
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(59.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(37.2mg,黄色油状，产率73％)，将目标产物测ee值(82％)。1H NMR(500MHz,CDCl3)δ7.28–7.25(m,1H),7.21–7.14(m,1H),6.93–6.84(m,4H),6.50–6.40(m,2H),4.61(t,J＝6.6Hz,1H),3.88(s,3H),2.17(s,3H),1.91–1.72(m,2H),0.95(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ157.2,145.5,131.8,129.7,127.7,127.4,126.2,120.8,113.5,110.6,55.5,54.6,29.7,20.5,11.2；HRMS(ESI)calcd.for C17H21NNaO[M+Na]+m/z 278.1515,found 278.1511；IR(neat,cm-1)2962,2921,1258,1026,804,751；m.p.70.8–72.2℃；[α]D 26＝–4.4(c＝1.5,CHCl3)；HPLC analysisCHIRALCEL OD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝5.7min,tR(major)＝6.9min。
实施例4
Figure BDA0003194919090000063
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(126μL,1.0mmol,5.0equiv)，接着加入上述烯烃(89.6mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(50.1mg,黄色油状，产率76％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.45–7.41(m,2H),7.41–7.36(m,2H),7.36–7.30(m,1H),7.27–7.23(m,2H),6.95–6.87(m,4H),6.45(d,J＝8.4Hz,2H),5.03(s,2H),4.15(t,J＝6.7Hz,1H),2.19(s,3H),1.86–1.72(m,2H),0.93(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ157.9,145.2,137.3,136.4,129.7,128.7,128.1,127.7,127.7,126.6,114.9,113.7,70.2,59.7,31.7,20.5,11.0；HRMS(ESI)calcd.for C23H25NNaO[M+Na]+m/z354.1828,found 354.1825；IR(neat,cm-1)3413,2919,1517,1233,802,761；[α]D 26＝–24.6(c＝1.5,CHCl3)；HPLC analysis CHIRALCEL OD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝12.5min,tR(minor)＝15.8min。
实施例5
Figure BDA0003194919090000071
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(90.4mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(43.3mg,黄色油状，产率65％)，将目标产物测ee值(87％)。1H NMR(500MHz,CD2Cl2)δ7.40–7.32(m,8H),7.32–7.27(m,1H),6.94(d,J＝8.4Hz,2H),6.48(d,J＝8.3Hz,2H),4.25(t,J＝6.8Hz,1H),2.22(s,3H),1.92–1.78(m,2H),1.00(t,J＝7.4Hz,3H)；13C NMR(126MHz,CD2Cl2)δ145.3,144.0,136.4,134.1,131.6,131.2,129.9,129.6,127.9,127.4,126.9,113.9,60.0,31.9,20.4,11.0；HRMS(ESI)calcd.for C22H23NNaS[M+Na]+m/z 356.1443,found 356.1446；IR(neat,cm-1)2962,2921,1517,1014,804,690；[α]D 26＝–46.5(c＝1.4,CHCl3)；HPLC analysis CHIRALCEL AD-Hcolumn,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝15.7min,tR(minor)＝18.1min。
实施例6
Figure BDA0003194919090000072
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(104.9mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(45.7mg,棕色油状，产率62％)，将目标产物测ee值(91％)。1H NMR(500MHz,CD2Cl2)δ7.31–7.26(m,2H),7.25–7.17(m,2H),6.88(d,J＝8.4Hz,2H),6.49(d,J＝8.3Hz,2H),4.72(s,2H),4.21(t,J＝6.8Hz,1H),2.17(s,3H),1.93–1.78(m,2H),0.96–0.90(m,12H),0.09(s,6H)；13C NMR(126MHz,CD2Cl2)δ144.6,143.9,142.2,129.9,128.7,127.5,125.7,125.3,125.1,114.6,65.4,61.1,31.6,26.1,20.5,18.7,11.0,-5.1；HRMS(ESI)calcd.for C23H35NNaOSi[M+Na]+m/z 392.2380,found392.2379；IR(neat,cm-1)2927,2856,1518,1099,835,775；[α]D 26＝–13.5(c＝1.1,CHCl3)；HPLC analysis CHIRALCEL AD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝4.4min,tR(major)＝4.9min。
实施例7
Figure BDA0003194919090000081
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(47.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(27.9mg,黄色油状，产率62％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.41–7.30(m,4H),7.27–7.22(m,1H),6.93(d,J＝6.5Hz,2H),6.56–6.40(m,2H),4.23(t,J＝6.6Hz,1H),2.22(s,3H),1.95–1.77(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ145.2,144.1,129.7,128.6,127.0,126.7,126.5,113.6,60.2,31.7,20.5,11.0；HRMS(ESI)calcd.for C16H19NNa[M+Na]+m/z248.1410,found 248.1409；IR(neat,cm-1)3407,2921,1617,1517,805,699；[α]D 26＝–20.3(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝5.5min,tR(major)＝6.2min。
实施例8
Figure BDA0003194919090000082
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(47.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(27.0mg,黄色油状，产率60％)，将目标产物测ee值(62％)。1H NMR(500MHz,CDCl3)δ7.41–7.30(m,4H),7.27–7.22(m,1H),6.93(d,J＝6.5Hz,2H),6.56–6.40(m,2H),4.23(t,J＝6.6Hz,1H),2.22(s,3H),1.95–1.77(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ145.2,144.1,129.7,128.6,127.0,126.7,126.5,113.6,60.2,31.7,20.5,11.0；HRMS(ESI)calcd.for C16H19NNa[M+Na]+m/z248.1410,found 248.1409；IR(neat,cm-1)3407,2921,1617,1517,805,699；[α]D 26＝–15.6(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝5.5min,tR(major)＝6.2min。
实施例9
Figure BDA0003194919090000083
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(67.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(32.4mg,浅黄色油状，产率59％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.84–7.77(m,4H),7.50–7.39(m,3H),6.87(d,J＝8.2Hz,2H),6.49(d,J＝8.4Hz,2H),4.36(t,J＝6.7Hz,1H),2.16(s,3H),1.94–1.85(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ145.3,141.7,133.6,132.9,129.7,128.4,128.0,127.8,126.6,126.0,125.6,125.4,125.0,113.7,60.4,31.7,20.5,11.0；HRMS(ESI)calcd.for C20H21NNa[M+Na]+m/z298.1566,found 298.1561；IR(neat,cm-1)3411,2922,1518,704,745,477；[α]D 26＝–10.3(c＝1.5,CHCl3)；HPLC analysisCHIRALCEL AD-H column,4％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝8.7min,tR(minor)＝9.8min。
实施例10
Figure BDA0003194919090000091
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(91.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(37.5mg,浅黄色油状，产率56％)，将目标产物测ee值(87％)。1H NMR(500MHz,CDCl3)δ7.59–7.47(m,4H),7.46–7.33(m,4H),6.91(d,J＝8.4Hz,2H),6.47(d,J＝8.4Hz,2H),4.24(t,J＝6.7Hz,1H),2.19(s,3H),1.93–1.78(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ145.1,143.7,139.6,138.6,133.3,129.8,129.0,128.4,127.2,127.2,126.7,113.7,59.9,31.7,20.5,11.0；HRMS(ESI)calcd.for C22H22ClNNa[M+Na]+m/z 358.1333,found 358.1333；IR(neat,cm-1)2940,2864,2167,1517,1014,814；[α]D 26＝–29.2(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL OD-Hcolumn,0.5％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝20.5min,tR(minor)＝26.1min。
实施例11
Figure BDA0003194919090000092
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(71.2mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(37.0mg,棕色油状，产率65％)，将目标产物测ee值(91％)。
1H NMR(500MHz,CDCl3)δ6.94–6.85(m,4H),6.83–6.78(m,1H),6.49–6.44(m,2H),4.12(t,J＝6.7Hz,1H),3.86(s,3H),3.85(s,3H),2.19(s,3H),1.87–1.73(m,2H),0.94(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ149.2,147.9,145.3,136.7,129.7,126.8,118.7,113.8,111.2,109.7,60.3,56.0,31.7,20.5,11.0；HRMS(ESI)calcd.for C18H23NNaO2[M+Na]+m/z 308.1621,found 308.1617；IR(neat,cm-1)2960,2929,1512,1257,1025,803；[α]D 26＝–22.7(c＝0.9,CHCl3)；HPLC analysis CHIRALCEL OD-H column,5％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝14.3min,tR(major)＝15.8min。
实施例12
Figure BDA0003194919090000101
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(73.6mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(30.3mg,棕色油状，产率52％)，将目标产物测ee值(85％)。1H NMR(500MHz,CDCl3)δ7.37–7.29(m,2H),7.06(d,J＝8.6Hz,2H),6.90(d,J＝8.1Hz,2H),6.48(t,J＝74.2Hz,1H),6.44–6.38(m,2H),4.19(t,J＝6.7Hz,1H),3.93(s,1H),2.18(s,3H),1.85–1.79(m,1H),1.79–1.73(m,1H),0.95(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ150.2,145.1,141.5,129.8,128.0,126.7,119.7,116.2(t,J＝259.0Hz),113.5,59.5,31.9,20.5,10.9；19F NMR(471MHz,CDCl3)δ-80.5；HRMS(ESI)calcd.forC18H23NNaO2[M+Na]+m/z 314.1327,found 314.1324；IR(neat,cm-1)2962,1518,1258,1011,865,787；[α]D 26＝–8.6(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,1％iPrOHin n-hexane,0.8mL/min,254nm UV detector,tR(major)＝60.9min,tR(minor)＝71.7min。
实施例13
Figure BDA0003194919090000102
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60.0mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(34.1mg,黄色油状，产率66％)，将目标产物测ee值(87％)。1H NMR(500MHz,CDCl3)δ7.32(d,J＝1.5Hz,1H),6.95(d,J＝8.3Hz,2H),6.54(d,J＝8.4Hz,2H),6.27(dd,J＝3.1,1.8Hz,1H),6.14(d,J＝3.1Hz,1H),4.41(t,J＝6.9Hz,1H),2.21(s,3H),1.94–1.76(m,2H),1.33–1.21(m,6H),0.88(t,J＝6.8Hz,3H)；13CNMR(126MHz,CDCl3)δ156.7,145.0,141.5,129.8,127.1,113.8,110.2,106.0,52.5,35.3,31.7,25.8,22.7,20.5,14.2；HRMS(ESI)calcd.for C17H23NO[M+H]+m/z 280.1672,found280.1668；IR(neat,cm-1)2923,2856,1518,1008,804,729；[α]D 26＝–74.4(c＝0.9,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝9.8min,tR(major)＝11.4min。
实施例14
Figure BDA0003194919090000111
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(66.4mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(38.2mg,棕色油状，产率70％)，将目标产物测ee值(84％)。1H NMR(500MHz,CD2Cl2)δ7.27(dd,J＝5.0,3.0Hz,1H),7.13–7.09(m,1H),7.03(dd,J＝5.0,1.2Hz,1H),6.90(d,J＝8.1Hz,2H),6.50–6.44(m,2H),4.43(t,J＝6.8Hz,1H),2.18(s,3H),1.82–1.72(m,2H),1.47–1.38(m,1H),1.35–1.25(m,5H),0.89(t,J＝7.1Hz,3H)；13C NMR(126MHz,CD2Cl2)δ146.6,145.8,129.9,126.7,126.5,126.1,120.9,113.7,54.6,38.2,32.1,26.3,23.0,20.4,14.2；HRMS(ESI)calcd.for C17H23NO[M+H]+m/z296.1443,found 296.1440；IR(neat,cm-1)2960,2925,1517,1258,1011,784；[α]D 26＝–32.5(c＝0.7,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,5％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝12.2min,tR(major)＝14.1min。
实施例15
Figure BDA0003194919090000112
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(59.6mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(32.2mg,棕色油状，产率63％)，将目标产物测ee值(80％)。1H NMR(500MHz,CDCl3)δ8.09(d,J＝2.3Hz,1H),7.57(dd,J＝8.5,2.4Hz,1H),6.91(d,J＝8.3Hz,2H),6.69(d,J＝8.5Hz,1H),6.48(d,J＝8.2Hz,2H),4.17(t,J＝6.8Hz,1H),3.91(s,3H),2.19(s,3H),1.95–1.83(m,1H),1.83–1.73(m,1H),0.93(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ163.6,145.6,144.1,137.1,131.4,129.8,127.6,114.3,111.1,58.0,53.5,31.2,20.5,10.8；HRMS(ESI)calcd.for C16H20N2NaO[M+Na]+m/z279.1468,found 279.1465；IR(neat,cm-1)3403,2923,1489,1279,1025,805；[α]D 26＝–1.6(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝15.0min,tR(minor)＝17.1min。
实施例16
Figure BDA0003194919090000121
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(126μL,1.0mmol,5.0equiv)，接着加入上述烯烃(73.6mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应48小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(36.6mg,棕色油状，产率63％)，将目标产物测ee值(86％)。1H NMR(500MHz,CDCl3)δ7.89–7.86(m,1H),7.70(d,J＝1.5Hz,1H),7.65–7.60(m,2H),7.45–7.39(m,2H),6.89(d,J＝8.1Hz,2H),6.50–6.36(m,3H),4.23(t,J＝6.7Hz,1H),2.18(s,3H),1.91–1.78(m,2H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ141.1,139.2,129.8,127.7,126.9,119.6,113.9,107.6,59.9,31.7,20.5,10.9；HRMS(ESI)calcd.for C19H21N3Na[M+Na]+m/z314.1628,found 314.1627；IR(neat,cm-1)3353,2920,1519,1029,798,758；[α]D 26＝–32.0(c＝1.0,CHCl3)；HPLC analysisCHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝15.2min,tR(minor)＝19.4min。
实施例17
Figure BDA0003194919090000122
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(126μL,1.0mmol,5.0equiv)，接着加入上述烯烃(64.8mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应48小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(38.7mg,棕色油状，产率72％)，将目标产物测ee值(90％)。1H NMR(500MHz,CD2Cl2)δ7.26–7.24(m,2H),6.89–6.84(m,4H),6.49–6.47(m,2H),4.25(t,J＝6.9Hz,1H),3.77(s,3H),2.17(s,3H),1.89–1.78(m,1H),1.78–1.67(m,1H),1.47–1.37(m,1H),1.33–1.28(m,1H),0.93(t,J＝7.4Hz,3H)；13C NMR(126MHz,CD2Cl2)δ159.1,144.8,136.3,129.8,128.0,114.5,114.1,58.5,55.6,41.1,20.5,19.9,14.1；HRMS(ESI)calcd.for C18H23NNaO[M+Na]+m/z 292.1672,found 292.1670；IR(neat,cm-1)2956,2929,1509,1242,1033,804；[α]D 26＝–30.2(c＝1.4,CHCl3)；HPLC analysisCHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝7.6min,tR(major)＝8.3min。
实施例18
Figure BDA0003194919090000123
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(126μL,1.0mmol,5.0equiv)，接着加入上述烯烃(52.0mg,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(27.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应48小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(26.6mg,棕色油状，产率56％)，将目标产物测ee值(85％)。1H NMR(500MHz,CDCl3)δ7.41(d,J＝7.5Hz,1H),7.21–7.09(m,3H),7.02(d,J＝8.2Hz,2H),6.64(d,J＝7.3Hz,2H),4.60(t,J＝4.9Hz,1H),2.88–2.72(m,2H),2.26(s,3H),2.05–1.95(m,2H),1.93–1.85(m,1H),1.83–1.73(m,1H)；13C NMR(126MHz,CDCl3)δ137.8,137.8,130.0,129.5,129.4,129.2,127.3,127.2,126.2,113.4,51.6,29.5,28.8,20.6,19.5；HRMS(ESI)calcd.for C17H19NNa[M+Na]+m/z 260.1410,found 260.1411；IR(neat,cm-1)2962 1616 1258 1083,1009,784；[α]D 26＝–6.0(c＝1.5,CHCl3)；HPLCanalysis CHIRALCEL OD-H column,6％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝6.6min,tR(major)＝7.7min。
实施例19
Figure BDA0003194919090000131
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(126μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(39.0mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(42.2mg,黑色油状，产率67％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.25(d,J＝8.6Hz,2H),7.00(d,J＝8.5Hz,2H),6.90–6.81(m,2H),6.49(d,J＝8.5Hz,2H),4.16(t,J＝6.7Hz,1H),3.79(s,3H),3.65(s,3H),3.46(s,2H),1.87–1.73(m,2H),0.94(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ172.8,158.6,146.6,135.8,130.0,127.6,122.4,114.0,113.6,59.4,55.3,52.0,40.4,31.7,10.9；HRMS(ESI)calcd.for C19H23NO3[M+H]+m/z 314.1751,found 314.1751；IR(neat,cm-1)3358,2919,1510,1244,1139,802；[α]D 26＝–21.5(c＝0.9,CHCl3)；HPLCanalysis CHIRALCEL OJ-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝24.3min,tR(major)＝27.1min。
实施例20
Figure BDA0003194919090000132
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(35.8mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应36小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(38.0mg,棕色油状，产率64％)，将目标产物测ee值(92％)。1H NMR(500MHz,CD2Cl2)δ7.29–7.24(m,2H),6.92–6.85(m,4H),6.54–6.48(m,2H),4.19(t,J＝6.8Hz,1H),3.79(s,3H),3.52(s,2H),2.09(s,3H),1.91–1.82(m,1H),1.81–1.74(m,1H),0.95(t,J＝7.4Hz,3H)；13C NMR(126MHz,CD2Cl2)δ207.2,159.0,146.7,136.2,130.4,127.9,123.3,114.1,113.9,59.6,55.6,50.2,32.0,29.3,11.0；HRMS(ESI)calcd.for C19H23NO2[M+H]+m/z 320.1621,found 320.1623；IR(neat,cm-1)3386,2921,1510,1244,1030,822；[α]D 26＝–35.7(c＝1.1,CHCl3)；HPLC analysis CHIRALCELOD-H column,8％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝44.9min,tR(major)＝47.8min。
实施例21
Figure BDA0003194919090000141
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(53.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(48.5mg,黄色油状，产率63％)，将目标产物测ee值(90％)。1H NMR(500MHz,CD2Cl2)δ7.27–7.23(m,2H),7.02(d,J＝8.4Hz,2H),6.88–6.84(m,2H),6.51–6.46(m,2H),4.53(s,2H),4.19(t,J＝6.8Hz,1H),3.77(s,3H),1.91–1.71(m,2H),0.96–0.92(t,J＝7.4Hz,3H),0.91(s,9H),0.07(s,6H)；13C NMR(126MHz,CD2Cl2)δ159.0,147.1,136.4,130.3,128.1,127.9,114.1,113.5,65.4,59.5,55.6,32.0,26.2,18.7,11.0,-5.1；HRMS(ESI)calcd.for C23H35NNaO2Si[M+Na]+m/z 408.2329,found408.2324；IR(neat,cm-1)2961,1613,1510,1257,1007,776；[α]D 26＝–31.7(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL OD-H column,1％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(major)＝8.5min,tR(minor)＝9.2min。
实施例22
Figure BDA0003194919090000142
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(47.4mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(59.6mg,黄色油状，产率84％)，将目标产物测ee值(90％)。1H NMR(500MHz,CD2Cl2)δ7.29–7.22(m,2H),7.04(t,J＝7.6Hz,1H),6.89–6.82(m,2H),6.74(d,J＝7.1Hz,1H),6.67–6.63(m,1H),6.49(dd,J＝8.1,2.4Hz,1H),4.19(t,J＝6.8Hz,1H),4.13(s,1H),3.77(s,3H),1.91–1.81(m,1H),1.81–1.71(m,1H),0.95(t,J＝7.4Hz,3H),0.91(t,J＝7.9Hz,9H),0.71(q,J＝7.9Hz,6H)；13C NMR(126MHz,CD2Cl2)δ159.0,147.2,138.2,136.6,128.6,128.0,123.2,119.6,114.2,114.0,59.5,55.6,32.1,11.0,7.6,3.7；HRMS(ESI)calcd.for C22H33NNaOSi[M+Na]+m/z 378.2224,found378.2222；IR(neat,cm-1)3409,2953,2873,1509,1243,715；[α]D 26＝–6.9(c＝1.4,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,1％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝29.2min,tR(major)＝38.5min。
实施例23
Figure BDA0003194919090000151
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(50.6mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(47.4mg黄色油状，产率64％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.27–7.21(m,2H),6.87–6.82(m,2H),6.62–6.56(m,2H),6.45–6.40(m,2H),4.09(t,J＝6.7Hz,1H),3.78(s,3H),1.90–1.81(m,1H),1.81–1.71(m,1H),0.94(s,9H),0.91(t,J＝7.4Hz,3H),0.12(s,6H)；13C NMR(126MHz,CDCl3)δ158.6,147.6,141.8,135.9,127.8,120.6,114.9,113.9,60.6,55.3,31.6,25.9,18.3,10.9,-4.4；HRMS(ESI)calcd.for C22H33NNaO2Si[M+Na]+m/z394.2173,found 394.2169；IR(neat,cm-1)2953,1612,1510,1257,1007,775；[α]D 26＝–25.5(c＝1.2,CHCl3)；HPLCanalysis CHIRALCEL OJ-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(major)＝8.1min,tR(minor)＝14.5min。
实施例24
Figure BDA0003194919090000152
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(30.6mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(34.7mg,黄色油状，产率64％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.30–7.23(m,2H),6.91–6.84(m,2H),6.74–6.67(m,2H),6.54–6.46(m,2H),4.13(t,J＝6.0Hz,1H),3.80(s,3H),3.71(s,3H),1.92–1.72(m,2H),0.95(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.6,152.0,141.8,136.1,127.7,114.8,114.8,114.0,60.2,55.9,55.3,31.8,10.9；HRMS(ESI)calcd.for C17H21NNaO2[M+Na]+m/z 294.1465,found 294.1465；IR(neat,cm-1)3403,2930,1507,1230,1032,816；[α]D 26＝–26.3(c＝1.3,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝37.7min,tR(minor)＝43.8min。
实施例25
Figure BDA0003194919090000161
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(45.8mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(40.2mg,黄色油状，产率58％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.42–7.34(m,4H),7.32–7.28(m,1H),7.26–7.23(m,2H),6.86(d,J＝8.5Hz,2H),6.76(d,J＝8.8Hz,2H),6.53(d,J＝8.8Hz,2H),4.94(s,2H),4.11(t,J＝6.7Hz,1H),3.79(s,3H),1.94–1.84(m,1H),1.84–1.74(m,1H),0.92(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,151.7,141.1,137.7,135.3,128,6,127.9,127.9,127.6,116.0,115.4,114.0,70.9,60.9,55.3,31.4,10.9；HRMS(ESI)calcd.forC23H25NNaO2[M+Na]+m/z 370.1778,found 370.1777；IR(neat,cm-1)3413,2919,1517,1233,802,761；[α]D 26＝–27.4(c＝1.3,CHCl3)；HPLC analysis CHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝15.9min,tR(minor)＝20.0min。
实施例26
Figure BDA0003194919090000162
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(43.0mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(43.4mg,黄色油状，产率65％)，将目标产物测ee值(90％)。1H NMR(500MHz,CD2Cl2)δ7.33–7.25(m,4H),7.01(t,J＝7.4Hz,1H),6.94–6.86(m,4H),6.84–6.78(m,2H),6.60–6.54(m,2H),4.18(t,J＝6.8Hz,1H),3.80(s,3H),1.95–1.84(m,1H),1.84–1.75(m,1H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CD2Cl2)δ159.4,159.1,148.0,144.2,135.9,129.9,128.1,122.4,121.2,117.5,114.9,114.2,60.3,55.6,31.9,11.0；HRMS(ESI)calcd.for C22H23NNaO2[M+Na]+m/z 356.1621,found356.1620；IR(neat,cm-1)3361,2919,1506,1223,825,691；[α]D 26＝–33.3(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝10.0min,tR(major)＝12.1min。
实施例27
Figure BDA0003194919090000171
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(33.8mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(35.6mg,黑色油状，产率62％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.25–7.20(m,2H),7.16–7.08(m,2H),6.88–6.79(m,2H),6.49(d,J＝8.3Hz,2H),4.15(t,J＝6.8Hz,1H),3.78(s,3H),2.36(s,3H),1.93–1.71(m,2H),0.92(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,145.9,135.3,131.3,127.7,124.6,114.4,114.0,59.7,55.3,31.5,19.1,10.9；HRMS(ESI)calcd.forC17H21NNaOS[M+Na]+m/z 310.1236,found 310.1231；IR(neat,cm-1)2962,1597,1498,1257,1010,795；[α]D 26＝–37.5(c＝0.5,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,5％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝59.7min,tR(minor)＝65.7min。
实施例28
Figure BDA0003194919090000172
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(30.0mg,1.0equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(46.2mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在15℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(39.4mg,棕色油状，产率56％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ:7.31–7.25(m,4H),7.24–7.19(m,2H),7.15–7.08(m,3H),6.93–6.88(m,2H),6.59–6.53(m,2H),4.22(t,J＝6.8Hz,1H),3.82(s,3H),1.94–1.77(m,2H),0.97(t,J＝7.4Hz,3H)；13C NMR(126MHz,CH2Cl2)δ:159.1,148.6,140.5,136.4,135.8,129.1,127.9,127.4,125.5,118.5,114.3,114.2,59.3,55.6,32.0,11.0；HRMS(ESI)calcd.for C22H23NNaOS[M+Na]+m/z 372.1393,found 372.1390；IR(neat,cm-1)2961,2923,1258,1082,1010,789；[α]D 26＝–45.4(c＝1.0,CHCl3)；HPLC analysisCHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝11.0min,tR(major)＝13.3min。
实施例29
Figure BDA0003194919090000173
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(24.6mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(36.7mg,黄色油状，产率76％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.27–7.24(m,2H),7.12–7.05(m,2H),6.88–6.83(m,2H),6.63(m,1H),6.52(d,J＝7.7Hz,2H),4.18(t,J＝6.7Hz,1H),3.79(s,3H),1.88–1.72(m,2H),0.94(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.6,147.5,135.9,129.2,127.7,117.3,114.0,113.5,59.4,55.3,31.7,10.9；HRMS(ESI)calcd.forC16H19NNaO[M+Na]+m/z 264.1359,found 264.1354；IR(neat,cm-1)3401,2929,1613,1254,761,692；[α]D 26＝–13.2(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝10.2min,tR(minor)＝13.4min。
实施例30
Figure BDA0003194919090000181
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基芳烃(30.6mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(41.7mg,黄色油状，产率77％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.29–7.26(m,2H),7.02(t,J＝8.1Hz,1H),6.90–6.86(m,2H),6.24(dd,J＝7.9,2.1Hz,1H),6.19(dd,J＝8.0,1.6Hz,1H),6.12(t,J＝2.2Hz,1H),4.19(t,J＝6.8Hz,1H),3.81(s,3H),3.72(s,3H),1.93–1.74(m,2H),0.95(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ160.7,158.6,148.8,135.7,129.9,127.7,114.0,106.8,102.6,99.6,59.6,55.4,55.1,31.6,10.9；HRMS(ESI)calcd.for C17H21NO2[M+H]+m/z272.1645,found 272.1640；IR(neat,cm-1)3401,2920,1610,1508,1160,825；[α]D 26＝–21.2(c＝1.2,CHCl3)；HPLC analysis CHIRALCEL OD-H column,15％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝9.9min,tR(minor)＝20.4min。
实施例31
Figure BDA0003194919090000182
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基苯(39.8mg,0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(39.3mg,黄色油状，产率62％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.54–7.49(m,2H),7.42–7.35(m,4H),7.30(d,J＝8.5Hz,2H),7.26–7.22(m,1H),6.90(d,J＝8.5Hz,2H),6.63(d,J＝8.4Hz,2H),4.25(t,J＝6.7Hz,1H),3.81(s,3H),1.97–1.76(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,146.9,141.4,135.7,130.2,128.7,127.9,127.7,126.4,126.1,114.1,113.8,59.4,55.3,31.7,11.0；HRMS(ESI)calcd.for C22H23NNaO[M+Na]+m/z 340.1672,found 340.1671；m.p.111.0–112.6℃；IR(neat,cm-1)3414,2926,1608,1246,761,693；[α]D 26＝–68.7(c＝1.2,CHCl3)；HPLC analysis CHIRALCEL AD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝11.9min,tR(minor)＝13.6min。
实施例32
Figure BDA0003194919090000191
氮气氛下，将氯化镍(II)六水合物(4.7mg,10mol％)，手性配体L*(9.5mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的c-hexane/1,4-dioxane(2:1,0.5mL)中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，乙醇(23μL，2.0equiv)接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基苯(31.4mg,0.20mmol,溶于c-hexane/1,4-dioxane(2:1,0.5mL)中),注射完毕后在15℃下反应36小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(32.4mg,黄色油状，产率59％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.25–7.20(m,2H),7.05–7.00(m,2H),6.89–6.83(m,2H),6.47–6.41(m,2H),4.14(t,J＝6.7Hz,1H),3.79(s,3H),1.90–1.71(m,2H),0.94(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,146.0,135.3,129.0,127.6,121.9,114.6,114.1,59.5,55.3,31.6,10.9；HRMS(ESI)calcd.for C16H18ClNNaO[M+Na]+m/z 298.0969,found 298.0964；IR(neat,cm-1)3412,2962,1495,1244,1031,811；[α]D 26＝–26.7(c＝1.0,CHCl3)；HPLCanalysis CHIRALCEL OJ-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(major)＝19.5min,tR(minor)＝23.6min.
实施例33
Figure BDA0003194919090000192
氮气氛下，将氯化镍(II)六水合物(4.7mg,10mol％)，手性配体L*(9.5mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的c-hexane/1,4-dioxane(2:1 0.5mL)中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，乙醇(23μL，2.0equiv)接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基苯(40.0mg,0.2mmol,溶于c-hexane/1,4-dioxane(2:1,0.5mL)中),注射完毕后在15℃下反应36小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(32.2mg,黄色油状，产率52％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.23–7.18(m,2H),7.17–7.11(m,2H),6.87–6.82(m,2H),6.41–6.35(m,2H),4.12(t,J＝6.7Hz,1H),3.78(s,3H),1.87–1.71(m,2H),0.93(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,146.6,137.7,135.3,131.9,127.6,115.0,114.1,59.3,55.4,31.7,10.9；HRMS(ESI)calcd.for C16H18BrNNaO[M+Na]+m/z 342.0464,found 342.0466；IR(neat,cm-1)2960,2925,1593,1493,1244,809；[α]D 26＝–24.3(c＝1.0,CHCl3)；HPLCanalysis CHIRALCEL OD-H column,5％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(minor)＝8.9min,tR(major)＝10.0min。
实施例34
Figure BDA0003194919090000201
氮气氛下，将氯化镍(II)六水合物(4.7mg,10mol％)，手性配体L*(9.5mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的c-hexane/1,4-dioxane(2:1 0.5mL)中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，乙醇(23μL，2.0equiv)接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基苯(37.8mg,0.2mmol,溶于c-hexane/1,4-dioxane(2:1 0.5mL)中),注射完毕后在15℃下反应36小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(32.5mg，黄色油状，产率53％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.25–7.20(m,2H),6.89–6.84(m,4H),6.49–6.44(m,2H),6.32(t,J＝75.0Hz,1H),4.12(t,J＝6.7Hz,1H),3.79(s,3H),1.88–1.73(m,2H),0.93(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,145.4,142.4,135.4,130.1,127.6,121.4,116.7(t,J＝258.6Hz),114.1,59.8,55.4,31.7,10.9；19F NMR(471MHz,CDCl3)δ-78.0；HRMS(ESI)calcd.for C17H19F2NNaO2[M+Na]+m/z 330.1276,found 330.1277；IR(neat,cm-1)2924,1518,1248,1069,1025,820；[α]D 26＝–10.2(c＝0.8,CHCl3)；HPLC analysis CHIRALCELOD-H column,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝7.3min,tR(major)＝8.1min。
实施例35
Figure BDA0003194919090000202
氮气氛下，将氯化镍(II)六水合物(4.7mg,10mol％)，手性配体L*(9.5mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的c-hexane/1,4-dioxane(2:1 0.5mL)中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，乙醇(23μL，2.0equiv)接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基苯(38.2mg,0.2mmol,溶于c-hexane/1,4-dioxane(2:1 0.5mL)中),注射完毕后在15℃下反应36小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(26.5mg，黄色油状，产率43％)，将目标产物测ee值(89％)。1H NMR(500MHz,CDCl3)δ7.31(d,J＝8.6Hz,2H),7.25–7.20(m,2H),6.90–6.84(m,2H),6.54(d,J＝8.5Hz,2H),4.21(t,J＝6.8Hz,1H),3.79(s,3H),1.92–1.77(m,2H),0.95(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ158.9,149.8,134.8,127.6,127.4,126.6(q,J＝3.8Hz),125.1(q,J＝270.3Hz),114.2,112.8,59.2,55.4,31.5,10.9；19F NMR(471MHz,CDCl3)δ-61.0；HRMS(ESI)calcd.for C17H18F3NO[M+H]+m/z 309.1340,found 309.1341；IR(neat,cm-1)2963,1614,1510,1099,1066,821；[α]D 26＝–10.3(c＝1.0,CHCl3)；HPLC analysisCHIRALCEL OJ-H column,15％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝13.7min,tR(minor)＝16.1min。
实施例36
Figure BDA0003194919090000211
氮气氛下，将氯化镍(II)六水合物(4.7mg,10mol％)，手性配体L*(9.5mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的c-hexane/1,4-dioxane(2:1 0.5mL)中，搅拌10分钟后加入(MeO)3SiH(136μL,1.1mmol,5.5equiv)，乙醇(23μL，2.0equiv)接着加入上述烯烃(60μL,0.40mmol)并置于0℃下，用注射器慢慢注入硝基苯(36.2mg,0.2mmol,溶于c-hexane/1,4-dioxane(2:1 0.5mL)中),注射完毕后在15℃下反应36小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(32.3mg，深黄色油状，产率54％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.37–7.27(m,2H),7.26–7.21(m,2H),7.12(t,J＝7.9Hz,1H),6.88–6.81(m,2H),6.70(d,J＝7.7Hz,1H),4.22(t,J＝6.8Hz,1H),3.85(s,3H),3.77(s,3H),1.93–1.76(m,2H),0.92(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ167.5,158.8,146.7,134.6,131.0,129.2,127.8,119.0,118.4,115.2,114.1,60.0,55.3,52.1,31.3,10.9；HRMS(ESI)calcd.for C18H21NNaO3[M+Na]+m/z 322.1414,found 322.1412；IR(neat,cm-1)2961,2925,1257,1011,795,684；[α]D 26＝–14.8(c＝1.4,CHCl3)；HPLC analysis CHIRALCEL AD-Hcolumn,10％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(minor)＝21.2min,tR(major)＝25.7min。
实施例37
Figure BDA0003194919090000212
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.50mmol,2.5equiv)，接着加入上述烯烃(30μL,0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(56.4mg,无色液体，产率82％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.49–7.44(m,4H),7.40–7.33(m,4H),7.31–7.24(m,2H),7.22–7.16(m,2H),6.99–6.94(m,2H),3.88(s,3H),3.87–3.83(m,2H),3.61(t,J＝7.5Hz,1H),3.20(d,J＝13.8Hz,2H),2.18–2.05(m,1H),1.89–1.76(m,1H),0.97(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.6,140.7,131.2,130.1,128.8,128.3,126.8,113.3,63.1,55.3,53.7,24.6,11.9；HRMS(ESI)calcd.for C24H27NNaO[M+Na]+m/z 368.1985,found368.1984；IR(neat,cm-1)2929,2857,1453,1009,731,696；[α]D 26＝–102.3(c＝1.2,CHCl3)；HPLC analysis CHIRALCEL OJ-H column,10％EtOH in n-hexane,0.8mL/min,220nm UVdetector,tR(major)＝7.2min,tR(minor)＝13.3min。
实施例38
Figure BDA0003194919090000213
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(29.6mg,0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(56.6mg,无色液体，产率82％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.45–7.40(m,4H),7.36–7.28(m,5H),7.26–7.21(m,2H),6.88–6.81(m,2H),6.80–6.76(m,1H),3.88–3.81(m,5H),3.58(t,J＝7.5Hz,1H),3.20(d,J＝13.9Hz,2H),2.14–2.02(m,1H),1.87–1.75(m,1H),0.94(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ159.4,140.9,140.6,128.9,128.9,128.3,126.8,121.6,115.2,112.0,63.9,55.3,53.8,24.5,11.9；HRMS(ESI)calcd.for C24H27NO[M+H]+m/z 368.1985,found368.1979；IR(neat,cm-1)2962,1452,1258,1010,787,696；[α]D 26＝–78.8(c＝1.5,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UVdetectorx,tR(major)＝5.4min,tR(minor)＝7.0min。
实施例39
Figure BDA0003194919090000221
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(29.6mg,0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(60.8mg,无色液体，产率88％)，将目标产物测ee值(84％)。1H NMR(500MHz,CDCl3)δ:7.40(d,J＝7.5Hz,4H),7.36–7.25(m,6H),7.25–7.19(m,2H),7.01(t,J＝7.4Hz,1H),6.94(d,J＝8.2Hz,1H),4.25(t,J＝7.7Hz,1H),3.85(d,J＝14.0Hz,2H),3.71(s,3H),3.24(d,J＝14.0Hz,2H),2.16–2.01(m,1H),1.85–1.71(m,1H),0.92(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.4,141.3,129.4,128.8,128.1,128.0,127.9,126.5,120.0,110.6,57.0,55.0,54.3,25.2,11.8；HRMS(ESI)calcd.for C24H27NNaO[M+Na]+m/z 368.1985,found 368.1980；IR(neat,cm-1)2954,2923,1452,1237,1028,740；[α]D 26＝–16.9(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝5.0min,tR(minor)＝6.2min。
实施例40
Figure BDA0003194919090000222
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(45.2mg,0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(56.4mg,无色液体，产率82％)，将目标产物测ee值(86％)。1H NMR(500MHz,CD2Cl2)δ7.61–7.33(m,14H),7.31–7.20(m,5H),3.83(d,J＝13.9Hz,2H),3.60(t,J＝7.4Hz,1H),3.21(d,J＝13.9Hz,2H),2.17–2.02(m,1H),1.87–1.75(m,1H),0.94(t,J＝7.3Hz,3H)；13C NMR(126MHz,CD2Cl2)δ140.8,138.9,136.3,134.2,131.3,131.0,130.3,129.6,129.1,128.6,127.4,127.1,63.8,54.1,24.3,11.9；HRMS(ESI)calcd.for C29H29NS[M+H]+m/z 446.1913,found 446.1912；IR(neat,cm-1)2960,2929,1492,1453,742,697；[α]D 26＝–113.0(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL AD-Hcolumn,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝5.7min,tR(minor)＝6.6min。
实施例41
Figure BDA0003194919090000231
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(52.5mg,0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(78.1mg,无色液体，产率85％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.42(d,J＝7.5Hz,4H),7.36–7.30(m,5H),7.26–7.20(m,4H),7.10(d,J＝7.5Hz,1H),4.80(s,2H),3.83(d,J＝13.9Hz,2H),3.60(t,J＝7.5Hz,1H),3.17(d,J＝13.9Hz,2H),2.14–2.03(m,1H),1.87–1.75(m,1H),0.98(s,9H),0.93(t,J＝7.3Hz,3H),0.14(s,6H)；13C NMR(126MHz,CDCl3)δ141.1,140.7,139.1,128.9,128.3,127.9,127.8,126.8,126.7,124.8,65.3,63.9,53.8,26.1,24.5,18.6,11.9,-5.0；HRMS(ESI)calcd.for C30H41NNaOSi[M+Na]+m/z 482.2850,found 482.2856；IR(neat,cm-1)2928,2855,1254,1027,835,697；[α]D 26＝–85.2(c＝1.2,CHCl3)；HPLC analysisCHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝3.9min,tR(minor)＝4.7min。
实施例42
Figure BDA0003194919090000232
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(23.6mg,0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(47.3mg,无色液体，产率75％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.47–7.37(m,6H),7.36–7.29(m,5H),7.28–7.22(m,4H),3.85(d,J＝13.9Hz,2H),3.62(t,J＝7.5Hz,1H),3.18(d,J＝13.9Hz,2H),2.18–2.01(m,1H),1.90–1.76(m,1H),0.95(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ140.6,139.1,129.1,128.9,128.3,128.0,127.0,126.8,63.9,53.8,24.4,11.9；HRMS(ESI)calcd.forC23H25NNa[M+Na]+m/z 338.1879,found 338.1879；IR(neat,cm-1)2961,2929,1493,1452,740,696；[α]D 26＝–72.5(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝4.7,tR(minor)＝5.8min。
实施例43
Figure BDA0003194919090000241
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率65％)，将目标产物测ee值(86％)。1H NMR(500MHz,CDCl3)δ7.42–7.29(m,10H),7.26–7.21(m,2H),7.16(d,J＝7.9Hz,2H),3.81(d,J＝13.8Hz,2H),3.59(t,J＝7.5Hz,1H),3.15(d,J＝13.8Hz,2H),2.13–2.01(m,1H),1.84–1.72(m,1H),0.92(t,J＝7.2Hz,3H)；13C NMR(126MHz,CDCl3)δ140.3,137.7,132.7,130.4,128.8,128.4,128.2,126.9,63.3,53.8,24.1,11.8；HRMS(ESI)calcd.for C23H24ClNNa[M+Na]+m/z372.1489,found 372.1485；IR(neat,cm-1)29611,2931,1512,1258,1027,697；[α]D 26＝–108.5(c＝0.9,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝4.7min,tR(minor)＝6.1min。
实施例44
Figure BDA0003194919090000242
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率62％)，将目标产物测ee值(87％)。1H NMR(500MHz,CDCl3)δ7.51(d,J＝8.3Hz,2H),7.42–7.37(m,4H),7.33(t,J＝7.6Hz,4H),7.24(t,J＝7.3Hz,2H),7.10(d,J＝8.3Hz,2H),3.81(d,J＝13.9Hz,2H),3.57(t,J＝7.5Hz,1H),3.15(d,J＝13.8Hz,2H),2.13–2.00(m,1H),1.83–1.71(m,1H),0.92(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ140.3,138.2,131.2,130.7,128.8,128.4,127.0,120.9,63.3,53.7,24.1,11.8；HRMS(ESI)calcd.for C23H24BrN[M+H]+m/z 394.1165,found 394.1167；IR(neat,cm-1)3358,2962,1258,1010,792,696；[α]D 26＝–106.7(c＝1.2,CHCl3)；HPLCanalysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(major)＝4.8min,tR(minor)＝6.3min。
实施例45
Figure BDA0003194919090000243
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率73％)，将目标产物测ee值(87％)。1H NMR(500MHz,CDCl3)δ7.42–7.37(m,4H),7.36–7.28(m,4H),7.25–7.18(m,4H),7.15–7.08(m,2H),6.54(t,J＝74.2Hz,1H),3.80(d,J＝13.8Hz,2H),3.59(t,J＝7.5Hz,1H),3.15(d,J＝13.9Hz,2H),2.13–1.99(m,1H),1.83–1.72(m,1H),0.91(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ150.25,140.35,136.51,130.35,128.81,128.38,126.93,118.97,116.2(t,J＝259.1Hz),63.20,53.75,24.20,11.81；19F NMR(471MHz,CDCl3)δ-80.49；HRMS(ESI)calcd.forC24H25F2NO[M+H]+m/z 381.1904,found；IR(neat,cm-1)2966,1525,1254,1023,795,696；[α]D 26＝–102.5(c＝1.3,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝5.8min,tR(minor)＝7.2min。
实施例46
Figure BDA0003194919090000251
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(浅黄色液体，产率68％)，将目标产物测ee值(86％)。1H NMR(500MHz,CDCl3)δ:7.49–7.38(m,5H),7.37–7.29(m,4H),7.26–7.20(m,2H),6.48–6.34(m,1H),6.23–6.10(m,1H),3.88(d,J＝13.8Hz,2H),3.71(t,J＝6.4Hz,1H),3.21(d,J＝13.9Hz,2H),2.00–1.87(m,1H),1.84–1.70(m,1H),1.51–1.38(m,1H),1.35–1.23(m,3H),1.20–1.09(m,2H),0.85(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ:155.4,141.6,140.6,129.0,128.3,126.8,109.7,107.8,55.4,54.5,31.7,31.0,26.4,22.7,14.2；HRMS(ESI)calcd.for C24H29NNaO[M+Na]+m/z 370.2141,found 370.2145；IR(neat,cm-1)2950,2852,1447,1025,788,685；[α]D 26＝–102.9(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OD-Hcolumn,0％iPrOH in n-hexane,1.0mL/min,215nm UV detector,tR(minor)＝8.6min,tR(major)＝14.2min。
实施例47
Figure BDA0003194919090000252
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(浅黄色液体，产率67％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.44–7.37(m,4H),7.36–7.29(m,5H),7.26–7.21(m,2H),7.08–7.05(m,1H),7.04–7.00(m,1H),3.81(d,J＝13.9Hz,2H),3.79–3.76(m,1H),3.19(d,J＝13.8Hz,2H),2.09–1.96(m,1H),1.81–1.68(m,1H),1.52–1.40(m,1H),1.34–1.18(m,6H),0.87(t,J＝7.1Hz,3H)；13C NMR(126MHz,CDCl3)δ141.1,140.6,128.9,128.3,128.3,126.9,124.8,122.4,57.3,53.9,32.1,32.0,26.8,22.8,14.2；HRMS(ESI)calcd.for C24H29NNaS[M+Na]+m/z 386.1913,found 386.1910；IR(neat,cm-1)2955,2856,1453,1027,783,696；[α]D 26＝–62.8(c＝1.4,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝4.7min,tR(minor)＝5.0min。
实施例48
Figure BDA0003194919090000261
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色液体，产率65％)，将目标产物测ee值(89％)。1H NMR(500MHz,CDCl3)δ7.95(d,J＝2.4Hz,1H),7.75(s,1H),7.70(d,J＝8.4Hz,2H),7.41(d,J＝7.8Hz,4H),7.36–7.28(m,6H),7.26–7.19(m,2H),6.50–6.47(m,1H),3.84(d,J＝13.8Hz,2H),3.65(t,J＝7.5Hz,1H),3.18(d,J＝13.8Hz,2H),2.17–2.05(m,1H),1.90–1.78(m,1H),0.94(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ141.1,140.4,139.2,137.6,130.0,128.8,128.4,126.9,126.9,118.9,107.7,63.4,53.8,24.2,11.8；HRMS(ESI)calcd.for C26H27N3[M+H]+m/z 381.2205,found；IR(neat,cm-1)2961,1523,1258,1027,796,697；[α]D 26＝–104.6(c＝1.3,CHCl3)；HPLC analysis CHIRALCEL AD-H column,1％iPrOH in n-hexane,0.5mL/min,254nm UV detector,tR(major)＝35.4min,tR(minor)＝38.2min。
实施例49
Figure BDA0003194919090000262
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(浅黄色液体，产率84％)，将目标产物测ee值(86％)。1H NMR(500MHz,CDCl3)δ7.46(s,1H),7.40(d,J＝7.6Hz,4H),7.32(t,J＝7.8Hz,5H),7.26–7.20(m,2H),6.40(s,1H),3.84(t,J＝7.3Hz,1H),3.78(d,J＝13.8Hz,2H),3.64(t,J＝6.7Hz,2H),3.24(d,J＝13.8Hz,2H),2.29–2.18(m,1H),1.98–1.88(m,1H),0.83(s,9H),-0.03(d,J＝13.7Hz,6H)；13C NMR(126MHz,CDCl3)δ142.8,140.7,140.3,128.8,128.4,126.9,122.4,110.9,61.1,54.1,50.4,35.5,26.1,18.4,-5.2,-5.3；HRMS(ESI)calcd.for C27H37NNaO2Si[M+Na]+m/z 458.2486,found 458.2480；IR(neat,cm-1)2951,2855,1254,1094,833,697；[α]D 26＝–35.2(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝4.6min,tR(minor)＝4.8min。
实施例50
Figure BDA0003194919090000271
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(95.2mg,0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(浅黄色液体，产率70％)，将目标产物测ee值(90％)。1H NMR(500MHz,CDCl3)δ7.43–7.36(m,6H),7.33(t,J＝7.4Hz,5H),7.26–7.19(m,4H),3.85(d,J＝13.8Hz,2H),3.69(t,J＝7.5Hz,1H),3.61(s,3H),3.12(d,J＝13.8Hz,2H),2.60–2.49(m,1H),2.47–2.28(m,2H),2.15–2.02(m,1H)；13C NMR(126MHz,CDCl3)δ174.2,140.1,137.9,129.1,128.9,128.4,128.2,127.4,127.0,61.3,53.7,51.6,31.8,26.6；HRMS(ESI)calcd.for C25H27NNaO2[M+Na]+m/z396.1934,found 396.1935；IR(neat,cm-1)3027,2949,1735,1435,744,697；[α]D 26＝–71.4(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL AD-Hcolumn,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝8.2min,tR(minor)＝10.0min。
实施例51
Figure BDA0003194919090000272
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色液体，产率83％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.45–7.38(m,2H),7.36–7.30(m,4H),7.26–7.21(m,1H),7.19–7.12(m,2H),6.96–6.85(m,4H),3.85(s,3H),3.81(s,3H),3.81–3.72(m,2H),3.57(t,J＝7.4Hz,1H),3.13(dd,J＝21.4,13.8Hz,2H),2.14–2.00(m,1H),1.85–1.73(m,1H),0.93(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.5,140.9,132.6,131.3,130.1,129.9,128.8,128.3,126.7,113.7,113.3,63.0,55.4,55.3,53.6,53.0,24.5,11.9；HRMS(ESI)calcd.forC25H29NNaO2[M+Na]+m/z 398.2091,found 398.2097；IR(neat,cm-1)2920,1509,1245,1034,806,697；[α]D 26＝–104.1(c＝1.2,CHCl3)；HPLC analysis CHIRALCEL OD-H column,1％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝7.3min,tR(minor)＝7.9min。
实施例52
Figure BDA0003194919090000273
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率78％)，将目标产物测ee值(92％)。1H NMR(500MHz,CD2Cl2)δ:7.44–7.40(m,2H),7.38–7.32(m,4H),7.27–7.22(m,3H),7.20–7.14(m,2H),6.96–6.91(m,2H),3.84(s,3H),3.78(dd,J＝23.2,13.9Hz,2H),3.54(t,J＝7.5Hz,1H),3.15(t,J＝14.6Hz,2H),2.49(s,3H),2.12–2.02(m,1H),1.85–1.74(m,1H),0.92(t,J＝7.3Hz,3H)；13C NMR(126MHz,CD2Cl2)δ:159.0,141.1,138.1,136.8,131.5,130.4,129.7,129.1,128.5,127.0,126.9,113.6,63.6,55.6,54.3,53.4,24.7,16.2,12.0；HRMS(ESI)calcd.for C25H29NNaOS[M+Na]+m/z 414.1862,found 414.1857；IR(neat,cm-1)2958,2927,1509,1247,798,698；[α]D 26＝–94.6(c＝1.2,CHCl3)；92％ee；HPLC analysis CHIRALCELAD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝7.2min,tR(minor)＝8.2min。
实施例53
Figure BDA0003194919090000281
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率86％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.60–7.48(m,4H),7.39(d,J＝7.6Hz,2H),7.33(t,J＝7.4Hz,2H),7.28–7.20(m,1H),7.16–7.10(m,2H),6.96–6.90(m,2H),3.85(s,3H),3.84–3.78(m,2H),3.53(t,J＝7.5Hz,1H),3.21(dd,J＝24.2,14.1Hz,2H),2.12–2.00(m,1H),1.86–1.74(m,1H),0.92(t,J＝7.2Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,145.1,140.2,130.9,130.1,129.2,128.9,128.8,128.4,127.7,125.2(q,J＝3.6Hz),124.5(q,J＝271.9Hz),113.5,63.6,55.4,53.9,53.5,24.6,11.9；19F NMR(471MHz,CDCl3)δ:-62.2；HRMS(ESI)calcd.forC25H26F3NNaO[M+Na]+m/z 436.1859,found 436.1858；IR(neat,cm-1)3359,3183,2918,1323,1065,697；[α]D 26＝–76.7(c＝0.9,CHCl3)；HPLC analysis CHIRALCEL AD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝5.2min,tR(minor)＝6.5min。
实施例54
Figure BDA0003194919090000282
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色液体，产率88％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.42(dd,J＝7.2,1.7Hz,1H),7.39–7.35(m,2H),7.33(t,J＝7.5Hz,2H),7.26–7.21(m,2H),7.15–7.10(m,2H),7.07(t,J＝8.7Hz,1H),6.95–6.91(m,2H),3.85(s,3H),3.75(dd,J＝41.1,13.9Hz,2H),3.52(t,J＝7.5Hz,1H),3.14(dd,J＝22.3,13.9Hz,2H),2.10–1.98(m,1H),1.86–1.74(m,1H),0.91(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,157.0(d,J＝247.0Hz),140.2,137.8(d,J＝3.6Hz),130.9,130.6,130.0,128.8,128.4,128.2(d,J＝6.9Hz),127.0,120.7(d,J＝17.5Hz),116.3(d,J＝20.9Hz),113.5,63.5,55.3,53.9,52.8,24.6,11.9；19F NMR(471MHz,CDCl3)δ-118.6；HRMS(ESI)calcd.forC24H25ClFNNaO[M+Na]+m/z 420.1501,found 420.1501；IR(neat,cm-1)2962,1258,1009,863,788,697；[α]D 26＝–85.1(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL AD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝5.4min,tR(minor)＝6.4min。
实施例55
Figure BDA0003194919090000291
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色液体，产率79％)，将目标产物测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.43–7.35(m,3H),7.31(t,J＝7.5Hz,2H),7.24–7.15(m,3H),6.94–6.87(m,2H),6.31(t,J＝2.4Hz,1H),6.17(d,J＝3.1Hz,1H),3.82(s,3H),3.80–3.73(m,2H),3.52(t,J＝7.3Hz,1H),3.32(dd,2H),2.12–1.99(m,1H),1.79–1.66(m,1H),0.84(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ158.6,153.9,141.7,140.6,132.4,129.9,128.7,128.3,126.8,113.5,110.2,108.1,64.7,55.4,53.9,46.2,25.4,11.5；19F NMR(471MHz,CDCl3)δ:-62.25；HRMS(ESI)calcd.for C22H25NNaO2[M+Na]+m/z358.1778,found 358.1774；IR(neat,cm-1)2928,1510,1250,1011,805,731；[α]D 26＝–98.1(c＝1.0,CHCl3)；HPLCanalysis CHIRALCEL AD-H column,1％iPrOH in n-hexane,0.8mL/min,254nm UVdetector,tR(major)＝6.5min,tR(minor)＝6.9min。
实施例56
Figure BDA0003194919090000292
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(浅黄色液体，产率87％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.45(d,J＝7.6Hz,2H),7.33(t,J＝7.5Hz,2H),7.26–7.21(m,2H),7.20–7.14(m,2H),6.96–6.88(m,4H),3.93(d,J＝14.4Hz,1H),3.88–3.82(m,4H),3.62(t,J＝7.5Hz,1H),3.46(d,J＝14.4Hz,1H),3.19(d,J＝14.0Hz,1H),2.13–2.01(m,1H),1.82–1.71(m,1H),0.93(t,J＝7.8Hz,3H)；13C NMR(126MHz,CDCl3)δ158.7,145.3,140.4,131.2,130.1,128.8,128.4,126.9,126.4,125.1,124.7,113.4,63.2,55.4,53.6,48.6,24.9,11.8；HRMS(ESI)calcd.for C22H25NNaOS[M+Na]+m/z 374.1549,found 374.1555；IR(neat,cm-1)3029,2960,1510,1252,1029,696；[α]D 26＝–85.8(c＝1.0,CHCl3)；HPLC analysisCHIRALCEL OD-H column,2％iPrOH in n-hexane,0.8mL/min,254nm UV detector,tR(major)＝5.5min,tR(minor)＝6.0min。
实施例57
Figure BDA0003194919090000301
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率83％)，将目标产物测ee值(95％)。1H NMR(500MHz,CDCl3)δ7.40–7.35(m,2H),7.32(t,2H),7.23(t,1H),7.13–7.08(m,2H),6.91–6.85(m,2H),3.82(s,3H),3.76(d,J＝14.2Hz,1H),3.50(t,J＝7.4Hz,1H),3.14(d,J＝14.2Hz,1H),2.29(dd,J＝12.5,9.4Hz,1H),2.05(d,J＝13.2Hz,1H),2.00–1.88(m,2H),1.80–1.60(m,5H),1.56–1.43(m,1H),1.24–1.08(m,3H),0.88(t,3H),0.81–0.69(m,2H)；13CNMR(126MHz,CDCl3)δ158.4,141.4,131.7,130.1,128.8,128.2,126.6,113.2,64.0,56.5,55.3,54.8,35.9,32.0,32.0,27.1,26.5,26.3,24.6,12.0；HRMS(ESI)calcd.forC24H33NNaO[M+Na]+m/z 374.2454,found 374.2452；IR(neat,cm-1)2921,1510,1254,1027,800,697；[α]D 26＝–95.6(c＝1.2,CHCl3)；HPLC analysis CHIRALCEL AD-H column(doublecolumn),0.5％iPrOH in n-hexane,0.5mL/min,254nm UV detector,tR(major)＝17.4min,tR(minor)＝20.8min。
实施例58
Figure BDA0003194919090000302
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(浅黄色液体，产率90％)，将目标产物测ee值(84％)。1H NMR(500MHz,CDCl3)δ7.16–7.04(m,2H),6.92–6.82(m,2H),3.80(s,3H),3.48(t,1H),2.13–2.05(m,2H),1.96–1.89(m,2H),1.89–1.79(m,1H),1.78–1.65(m,3H),0.92(d,J＝6.5Hz,6H),0.88(t,J＝7.3Hz,3H),0.80(d,J＝6.6Hz,6H)；13C NMR(126MHz,CDCl3)δ158.3,132.4,130.1,113.1,65.0,59.2,55.3,26.6,24.4,21.1,21.0,12.2；HRMS(ESI)calcd.forC18H31NNaO[M+Na]+m/z 300.2298,found 300.2293；IR(neat,cm-1)2962,1608,1510,1248,833,772；[α]D 26＝–23.1(c＝0.8,CHCl3)；1H NMR analysis of the amine with(R)-O-acetylmandelic acid and(S)-O-acetylmandelic acid,repectively.It indicated84％ee。
实施例59
Figure BDA0003194919090000303
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的THF(1.0mL,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，接着加入上述烯烃(0.20mmol,1.0equiv)以及N-OBz(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(无色液体，产率72％)，将目标产物测dr值(95:5)。1H NMR(500MHz,CDCl3)δ7.44(d,J＝7.4Hz,2H),7.34–7.27(m,5H),7.26–7.21(m,3H),7.20–7.13(m,2H),6.92–6.87(m,2H),4.07(q,J＝6.8Hz,1H),3.82(s,3H),3.78(d,J＝14.9Hz,1H),3.62(d,J＝14.9Hz,1H),3.58(dd,J＝9.8,4.9Hz,1H),1.81–1.73(m,1H),1.57–1.50(m,1H),1.12(d,J＝6.8Hz,3H),0.63(t,J＝7.3Hz,3H)；13C NMR(126MHz,CD2Cl2)δ158.9,145.8,143.3,135.2,129.9,128.3,128.2,128.2,128.2,126.8,126.5,113.8,65.4,56.7,55.5,50.9,25.9,14.5,12.0；HRMS(ESI)calcd.for C25H29NNaO[M+Na]+m/z 382.2141,found382.2143；IR(neat,cm-1)2956,1609,1510,1249,1027,698；[α]D 26＝–2.4(c＝1.0,CHCl3)；1H NMR analysis indicated 95:5dr。
实施例60
Figure BDA0003194919090000311
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/THF(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，CH3OH(20μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率80％)，将目标产物测ee值(92％)。1H NMR(500MHz,CD2Cl2)δ7.84–7.77(m,2H),7.57–7.51(m,1H),7.48–7.42(m,2H),7.36–7.30(m,2H),6.95–6.86(m,2H),6.67(s,1H),5.05–4.95(m,1H),3.82(s,3H),1.99–1.89(m,2H),0.98(t,J＝7.4Hz,3H)；13C NMR(126MHz,CD2Cl2)δ166.9,159.2,135.4,135.0,131.7,128.9,128.1,127.2,114.2,55.6,55.3,29.7,11.1；HRMS(ESI)calcd.for C17H19NNaO2[M+Na]+m/z 292.1308,found 292.1303；IR(neat,cm-1)3327,2966,1629,1511,1245,692；[α]D 23＝–31.3(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL OD-Hcolumn,10％EtOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝6.9min,tR(major)＝7.8min。
实施例61
Figure BDA0003194919090000312
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/THF(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，CH3OH(20μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率74％)，将目标产物测ee值(93％)。1H NMR(500MHz,CDCl3)δ7.81–7.73(m,2H),7.51–7.46(m,1H),7.44–7.38(m,2H),7.39–7.30(m,4H),7.29–7.25(m,1H),6.42(s,1H),5.14–5.05(m,1H),2.01–1.88(m,2H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ167.0,142.2,134.8,131.6,128.8,128.7,127.5,127.0,126.8,55.5,29.3,11.0；HRMS(ESI)calcd.for C16H17NNaO[M+Na]+m/z 262.1202,found 262.1198；IR(neat,cm-1)3320,2963,1633,1526,1489,699；m.p.111.3–113.2℃；[α]D 23＝–23.2(c＝0.8,CHCl3)；HPLC analysis CHIRALCEL OD-Hcolumn,10％iPrOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝9.2min,tR(major)＝14.5min。
实施例62
Figure BDA0003194919090000321
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/DMA(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，tBuOH(46μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率79％)，将目标产物测ee值(92％)。1H NMR(500MHz,CDCl3)δ7.80–7.72(m,2H),7.54–7.45(m,1H),7.44–7.36(m,2H),6.93–6.82(m,3H),6.31(d,J＝7.8Hz,1H),5.09–4.94(m,1H),3.87(s,3H),3.86(s,3H),2.03–1.86(m,2H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ166.9,149.2,148.5,134.9,134.8,131.6,128.7,127.0,118.6,111.4,110.6,56.1,55.3,29.2,11.1；HRMS(ESI)calcd.for C18H21NNaO3[M+Na]+m/z 322.1414,found 322.1410；IR(neat,cm-1)3312,2928,1630,1515,1261,1141；m.p.133.5–135.0℃；[α]D 23＝–19.2(c＝1.1,CHCl3)；HPLC analysis CHIRALCEL AD-H column,15％EtOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝8.6min,tR(major)＝15.4min。
实施例63
Figure BDA0003194919090000322
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/DMA(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，tBuOH(46μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率67％)，将目标产物测ee值(88％)。1H NMR(500MHz,CDCl3)δ7.78–7.73(m,2H),7.54–7.39(m,5H),7.25–7.19(m,2H),6.36(d,J＝7.9Hz,1H),5.14–4.79(m,1H),1.96–1.85(m,2H),0.96(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ167.0,141.4,134.5,131.9,131.7,128.8,128.5,127.0,121.3,55.0,29.2,10.9；HRMS(ESI)calcd.for C16H16BrNNaO[M+Na]+m/z 340.0307,found 340.0304；IR(neat,cm-1)3294,2969,1632,1529,1488,691；m.p.167.2–167.8℃；[α]D 23＝–6.0(c＝1.0,CHCl3)；HPLC analysis CHIRALCEL OD-H column,20％iPrOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝5.4min,tR(major)＝7.3min。
实施例64
Figure BDA0003194919090000331
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/DMA(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，tBuOH(46μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率70％)，将目标产物测ee值(89％)。1H NMR(500MHz,CDCl3)δ7.77–7.68(m,2H),7.30–7.26(m,2H),6.93–6.86(m,4H),6.16(d,J＝7.6Hz,1H),5.16–4.91(m,1H),3.84(s,3H),3.79(s,3H),2.00–1.84(m,2H),0.94(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ166.3,162.3,159.0,134.5,128.8,128.0,127.2,114.2,113.9,55.6,55.4,54.9,29.2,11.0；HRMS(ESI)calcd.forC18H21NNaO3[M+Na]+m/z 322.1414,found 322.1412；IR(neat,cm-1)3326,2930,1626,1505,1245,1030；m.p.175.9–176.4℃；[α]D 23＝–2.7(c＝0.5,CHCl3)；HPLC analysis CHIRALCELOD-H column,15％iPrOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝10.9min,tR(major)＝14.1min。
实施例65
Figure BDA0003194919090000332
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/DMA(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，tBuOH(46μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率59％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.72–7.64(m,2H),7.41–7.33(m,2H),7.28–7.25(m,2H),6.90–6.83(m,2H),6.29(d,J＝8.0Hz,1H),5.09–4.86(m,1H),3.79(s,3H),2.03–1.83(m,2H),0.93(t,J＝7.4Hz,3H)；13C NMR(126MHz,CDCl3)δ165.8,159.1,137.7,134.0,133.2,128.9,128.5,128.0,114.2,55.4,55.1,29.1,11.0；HRMS(ESI)calcd.forC17H18ClNNaO2[M+Na]+m/z 326.0918,found 326.0915；IR(neat,cm-1)3320,2963,1634,1514,1265,735；m.p.151.7–153.2℃；[α]D 23＝–6.7(c＝0.5,CHCl3)；HPLC analysisCHIRALCEL OD-H column,15％iPrOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝6.9min,tR(major)＝9.6min。
实施例66
Figure BDA0003194919090000341
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/DMA(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，tBuOH(46μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率65％)，将目标产物测ee值(91％)。1H NMR(500MHz,CDCl3)δ7.83(d,J＝8.1Hz,2H),7.64(d,J＝8.0Hz,2H),7.31–7.24(m,2H),6.92–6.84(m,2H),6.50(s,1H),5.19–4.82(m,1H),3.79(s,3H),2.02–1.86(m,2H),0.94(t,J＝7.3Hz,3H)；13C NMR(126MHz,CDCl3)δ165.7,159.1,138.1,133.9,133.2(q,J＝32.8Hz),128.0,127.5,125.7(q,J＝3.8Hz),123.8(q,J＝272.6Hz),114.3,55.4,55.3,29.1,11.0；19F NMR(471MHz,CDCl3)δ-63.0；HRMS(ESI)calcd.for C18H18F3NNaO2[M+Na]+m/z 360.1182,found 360.1180；IR(neat,cm-1)3315,2963,1634,1514,1265,735；[α]D 23＝–20.7(c＝1.2,CHCl3)；HPLC analysis CHIRALCEL OD-H column,15％iPrOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝5.9min,tR(major)＝8.9min。
实施例67
Figure BDA0003194919090000342
氮气氛下，将氯化镍(II)六水合物(2.4mg,5mol％)，手性配体L*(4.4mg,7mol％)，碘化钠(4.5mg,0.15equiv)溶于干燥的1,4-dioxane/THF(4:1,0.20M)中，搅拌10分钟后加入(MeO)3SiH(64μL,0.5mmol,2.5equiv)，CH3OH(20μL,2.4equiv),接着加入上述烯烃(0.20mmol,1.0equiv)以及恶唑酮(0.30mmol,1.5equiv)后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(白色固体，产率69％)，将目标产物测ee值(92％)。1H NMR(500MHz,CD2Cl2)δ7.29–7.23(m,2H),7.21–7.15(m,3H),7.13–7.08(m,2H),6.86–6.81(m,2H),5.71(s,1H),4.79–4.69(m,1H),3.78(s,3H),2.91(t,J＝7.6Hz,2H),2.54–2.38(m,2H),1.72–1.68(m,2H),0.80(t,J＝7.4Hz,3H)；13C NMR(126MHz,CD2Cl2)δ171.4,159.1,141.5,135.1,128.8,128.7,128.0,126.5,114.1,55.6,54.6,38.8,32.0,29.5,10.9；HRMS(ESI)calcd.for C19H23NNaO2[M+Na]+m/z 320.1621,found320.1619；IR(neat,cm-1)3290,2930,1640,1511,1245,699；m.p.111.9–112.3℃；[α]D 23＝–51.5(c＝0.7,CHCl3)；HPLC analysis CHIRALCEL OD-H column,10％iPrOH in n-hexane,1.0mL/min,254nm UV detector,tR(minor)＝15.2min,tR(major)＝20.1min。
对比例1
Figure BDA0003194919090000343
氮气氛下，将碘化镍水合物(8.4mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率62％)，将目标产物测ee值(93％)。结论：碘化镍水合物代替四氟硼酸镍(II)六水合物结果显示：对映选择性虽无影响，但收率降低了14％。
对比例2
Figure BDA0003194919090000351
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L1*(7.6mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率29％)，将目标产物测ee值(60％)。结论：手性配体L1*代替手性配体L*结果显示:对映选择性差、收率降低明显。
对比例3
Figure BDA0003194919090000352
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L2*(7.6mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率14％)，将目标产物测ee值(33％)。结论：手性配体L2*代替手性配体L*结果显示:对映选择性差、收率降低明显。
对比例4
Figure BDA0003194919090000353
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L3*(7.6mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率14％)，将目标产物测ee值(33％)。结论：手性配体L3*代替手性配体L*结果显示:对映选择性非常差、收率降低明显。
对比例5
Figure BDA0003194919090000354
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(7.6mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)2MeSiH(123μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率10％)，将目标产物测ee值(89％)。结论：二甲氧基甲基硅氢代替三甲氧基硅氢结果显示：对映选择性影响不大，但收率降低过于明显。
对比例6
Figure BDA0003194919090000361
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锰(26.4mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率32％)，将目标产物测ee值(87％)。结论：还原剂锰粉代替锌粉结果显示：对映选择性影响不大，但收率降低明显。
对比例7
Figure BDA0003194919090000362
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钾(16.6mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在0℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率18％)，将目标产物测ee值(85％)。结论：添加剂碘化钾代替碘化钠结果显示：对映选择性影响不大，但收率降低明显。
对比例8
Figure BDA0003194919090000363
氮气氛下，将四氟硼酸镍(II)六水合物(6.8mg,10mol％)，手性配体L*(8.2mg,13mol％)，碘化钠(15.0mg,0.5equiv)，锌(31.0mg,2.4equiv),氟化铝(62.0mg,3.7equiv)溶于干燥的0.5mL甲苯中，搅拌10分钟后加入(MeO)3SiH(127μL,1.0mmol,5.0equiv)，接着加入上述烯烃并置于0℃下，用注射器慢慢注入硝基芳烃(0.20mmol,1.0equiv，溶于0.5mL甲苯),注射完毕后在25℃下反应24小时。反应结束后，减压浓缩除去反应溶剂，柱层析分离纯化得到目标产物(黄色油状，产率58％)，将目标产物测ee值(87％)。结论：反应温度25℃代替0℃结果显示：对映选择性有轻微降低，收率也有降低。

Claims (10)

1.一种镍催化烯烃的不对称氢胺化方法，其特征在于，包括以下步骤：在惰性气体中，将金属镍类催化剂、手性配体L*、氢源、添加剂溶于有机溶剂中，然后加入烯烃
Figure FDA0003194919080000011
和胺源Ar-NO2、R2R3NOBz、
Figure FDA0003194919080000012
中的一种，得到反应混合物，后处理纯化得到目标产物(
Figure FDA0003194919080000013
或其对映体
Figure FDA0003194919080000014
)；
其中，R1为烯烃的末端取代基，为氢原子、烷基、芳基、酯基、酰胺、胺基、保护的胺基、硅醚中的任一种；
R2结构为芳基(Aryl)、烷基(Alkyl)或氢原子(H)中的一种；
R3结构为芳基(Aryl)、烷基(Alkyl)或氢原子(H)中的一种；
Ar为取代芳基或杂芳基；
所述的手性配体L*为Biox配体，结构式为：
Figure FDA0003194919080000015
或其对映体
Figure FDA0003194919080000016
2.根据权利要求1所述的镍催化烯烃的不对称氢胺化方法，其特征在于：
制备路线1：
Figure FDA0003194919080000017
路线1中的Ni(BF4)2·6H2O为镍类催化剂四氟硼酸镍(II)六水合物，手性配体L*为
Figure FDA0003194919080000018
或其对映体
Figure FDA0003194919080000019
(MeO)3SiH为氢源三甲氧基硅烷，NaI为添加剂碘化钠，Zn为还原剂锌粉，AlF3为碱三氟化铝，toluene为溶剂甲苯；
制备路线2：
Figure FDA00031949190800000110
路线2中的NiCl2·6H2O为镍类催化剂氯化镍(II)六水合物，手性配体L*为
Figure FDA00031949190800000111
或其对映体
Figure FDA00031949190800000112
(MeO)3SiH为氢源三甲氧基硅烷，NaI为添加剂碘化钠，THF为溶剂为四氢呋喃；
制备路线3：
Figure FDA0003194919080000021
路线3中的NiCl2·6H2O为镍类催化剂氯化镍(II)六水合物，手性配体L*为
Figure FDA0003194919080000022
或其对映体
Figure FDA0003194919080000023
(MeO)3SiH为氢源三甲氧基硅烷，NaI为添加剂1碘化钠，CH3OH为添加剂2甲醇，1,4-dioxane/THF为溶剂1,4-二氧六环/四氢呋喃。
3.根据权利要求1所述的镍催化烯烃的不对称氢胺化方法，其特征在于：所述Ar中芳基上的取代基为氢原子、氟原子、氯原子、溴原子、烷氧基、含氟烷基、硫醚、酚羟基、酮、醛、酯基、胺基、保护的胺基、酰胺、芳环、杂芳基的任一种；杂芳基为吡啶、呋喃、噻吩、吡唑、吲哚中的任一种。
4.根据权利要求1所述的镍催化烯烃的不对称氢胺化方法，其特征在于：所述金属镍类催化剂是金属镍盐、氢源是硅氢或硼氢频哪醇硼烷或硼烷二甲硫醚、添加剂是碘的无机盐。
5.根据权利要求2所述的镍催化烯烃的不对称氢胺化方法，其特征在于：路线1所述的镍催化烯烃的不对称氢芳胺化方法，在–10℃～40℃下和溶剂中，在金属镍类催化剂、手性配体L*、氢源、添加剂、还原剂、碱存在的条件下，烯烃和胺源反应1小时～48小时；所述的金属镍类催化剂、手性配体L*、氢源、添加剂、还原剂、碱、烯烃和胺源的摩尔比是(0–0.20)：(0–0.30)：(1.0–6.0)：(0–3.0)：(1.0–4.0)：(1.0–4.0)：(1.0–4.0)：(1.0–4.0)；所述的反应时间以检测反应完全为止。
6.根据权利要求2所述的镍催化烯烃的不对称氢胺化方法，其特征在于：路线2所述的镍催化烯烃的不对称氢烷基胺化方法，在–10℃～40℃下和溶剂中，在金属镍类催化剂、手性配体L*、氢源、添加剂存在的条件下，烯烃和胺源反应1小时～48小时；所述的金属镍类催化剂、手性配体L*、氢源、添加剂、烯烃和胺源的摩尔比是(0–0.20)：(0–0.30)：(1.0–6.0)：(0–3.0)：(1.0–4.0)：(1.0–4.0)；所述的反应时间以检测反应完全为止。
7.根据权利要求2所述的镍催化烯烃的不对称氢胺化方法，其特征在于：路线3所述的镍催化烯烃的不对称氢酰胺化方法，在–10℃～40℃下和溶剂中，在金属镍类催化剂、手性配体L*、氢源、添加剂1和添加剂2存在的条件下，烯烃和胺源反应1小时～48小时；所述的金属镍类催化剂、手性配体L*、氢源、添加剂1、添加剂2、烯烃和胺源的摩尔比是(0–0.20)：(0–0.30)：(1.0–4.0)：(0–3.0)：(0–4.0)：(1.0–4.0)；所述的反应时间以检测反应完全为止。
8.根据权利要求1所述的镍催化烯烃的不对称氢胺化方法，其特征在于，所述的金属镍盐是氯化镍、氯化镍六水合物、氯化镍乙二醇二甲醚复合物、溴化镍、溴化镍三水合物、溴化镍二乙二醇二甲醚复合物、溴化镍乙二醇二甲醚复合物、双-(1,5-环辛二烯)镍复合物、硝酸镍六水合物、高氯酸镍六水合物、四氟硼酸镍六水合物中的任一种；
所述的氢源为聚甲基氢硅氧烷(PMHS)、三甲氧基硅烷、三乙氧基硅烷、二乙氧基甲基硅烷(DEMS)、苯基硅烷、二苯基硅烷、三苯基硅烷、三乙基硅烷、硼烷二甲硫醚、频哪醇硼烷中的任一种；
所述的添加剂为氯化锂、氯化钠、溴化锂、溴化钾、溴化镁、溴化镁水合物、碘化锂、碘化钠、碘化锌、碘化镁、四丁基氯化铵、四丁基溴化铵、四丁基碘化铵、乙酸钠、乙酸钾、甲醇、异丙醇、叔丁醇、六氟异丙醇、苄醇、乙腈中的一种或多种；
所述的溶剂为四氢呋喃、1,4-二氧六环、乙二醇二甲醚、二乙二醇二乙醚、甲苯、二甲苯、三甲苯、三氟甲苯、1,2-二氯乙烷、氯仿、乙腈、N,N-二甲基乙酰胺、N,N-二甲基甲酰胺、N,N-二甲基丙烯基脲、N-甲基吡咯烷酮、二甲基亚砜、甲醇、乙醇和水中的一种或多种。
9.根据权利要求1所述的镍催化烯烃的不对称氢胺化方法，其特征在于：胺源为Ar-NO2反应中还需增加碱，其阳离子为Li+、Na+、K+、Cs+、Mg2+和Al3+中的任一种，阴离子为[CO3]2-、[HCO3]-、[PO4]3-、[HPO4]2-、[H2PO4]-、F-、[OH]-、[CH3COO]-、[OMe]-和[OtBu]-中的任一种。
10.根据权利要求1所述的镍催化烯烃的不对称氢胺化方法，其特征在于：所述的烯烃为反式构型的烯烃，结构式如下：
Figure FDA0003194919080000031
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