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CN110734378A - 一种高化学及立体选择性制备手性烯丙基胺类化合物的方法 - Google Patents

一种高化学及立体选择性制备手性烯丙基胺类化合物的方法 Download PDF

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CN110734378A
CN110734378A CN201910886513.XA CN201910886513A CN110734378A CN 110734378 A CN110734378 A CN 110734378A CN 201910886513 A CN201910886513 A CN 201910886513A CN 110734378 A CN110734378 A CN 110734378A
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chiral
allylamine
cdcl
nmr
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CN110734378B (zh
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阴国印
龙姣
王鹏
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Wuhan University WHU
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Abstract

本发明公开了一种高化学及立体选择性制备手性烯丙基胺类化合物的方法。在金属试剂Ni(COD)2、手性双膦配体和

Description

一种高化学及立体选择性制备手性烯丙基胺类化合物的方法
技术领域
本发明属于有机合成领域，具体涉及一种高化学及立体选择性制备手性烯丙基胺类化合物的方法及应用。
背景技术
手性胺片段广泛存在于天然产物以及生物活性分子中[a)Lough,W.J.； Wainer,I.W.Chirality in Natural and Applied Science,Blackwell:Oxford,UK,2002；b)Francotte E.；Lindner,W.Chirality in Drug Research,Wiley-VCH:Weinheim, 2006；c)Nugent,T.C.Chiral Amine Synthesis:Methods,Developments and Applications,Wiley-VCH:Weinheim,2010]。基于其重要的应用价值，手性胺的合成在有机化学领域引起了极大的兴趣和广泛的关注[a)Li,W.；Zhang,X. Stereoselective Formation ofAmines,2014；b)Nugent,T.C.；El-Shazly,M.Adv. Synth.Catal.2010,352,753-819；c)Patil,M.D.；Grogan,G.；Bommarius,A.；Yun, H.ACS Catal.2018,8,10985-11015；d)Grogan,G.Curr.Opin.Chem.Biol.2018,43, 15-22]。氢胺化反应是一种含有N-H键的化合物直接向不饱和碳碳双键或者三键加成，从而构建新的C-N键的反应。该反应符合原子经济性和绿色化学的策略，是合成手性胺类化合物最有效的方法之一。
过渡金属催化的联烯，炔烃以及共轭烯烃的不对称氢胺化反应已有报道[a)Lutete,L.M.；Kadota,I.；Yamamoto,Y.J.Am.Chem.Soc.2004,126,1622-1623；b) Cooke,M.L.；Xu,K.；Breit,B.Angew.Chem.Int.Ed.2012,51,10876-10879；c)Xu, K.；Wang,Y.H.；Khakyzadeh,V.；Breit,B.Chem.Sci.2016,7,3313-3316；d)Athira, C.；Changotra,A.；Sunoj,R.B.J.Org.Chem.2018,83,2627-2639；e)Xiong,Y.；Sun, Y.W.；Zhang,G.Z.Tetrahedron Lett.2018,59,347-355；f)Park,S.；Malcolmson,S. J.ACSCatal.2018,8,8468-8476；g)Berthold,D.；Geissler,A.G.A.；Giofre,S.；Breit,B.Angew.Chem.Int.Ed.2019,58,9994-9997],但大都局限在Rh,Pd等贵金属催化剂，而且底物范围较为狭窄，官能团的容忍性较差。此外，为了提高反应的转化率，通常需要使用大过量的不饱和底物。
因此，如何在温和的条件下实现廉价金属催化的高化学及立体选择性不对称氢胺化反应亟待解决。
发明内容
本发明的目的在于提供一种廉价金属催化的高化学及立体选择性制备手性烯丙基胺类化合物的方法，该方法操作简便，原料廉价易得，反应条件温和，底物官能团容忍性好，具有优秀的化学选择性和立体选择性。
本发明实现上述目的采用以下技术方案：
一种高化学及立体选择性制备手性烯丙基胺类化合物的方法，包括以下步骤：在金属试剂Ni(COD)2(二(1，5-环辛二烯)镍)、手性双膦配体和酸添加剂作用下，将1,3-共轭二烯、胺溶于有机溶剂中并进行反应，经柱层析分离纯化得到手性烯丙基胺类化合物；
所述方法合成路线如下：
优选地，所述1,3-共轭二烯为1-芳基或烷基取代的1,3-丁二烯，进一步优选地，取代基R包括：苯基、2-甲氧基苯基、4-甲氧基苯基、4-氟苯基、4-三氟甲基苯基、4-二甲氨基苯基、2-呋喃基、环己基。
优选地，所述胺包括：正丁胺、2-苯乙胺、环丙胺、环己胺、糠胺、2-(1- 环己烯基)乙胺、烯丙基胺、(±)-四氢糠胺、N,N-二甲基乙二胺、苄胺、甘氨酸甲酯、(S)-1-苯乙胺、苯胺、4-甲基苯胺、4-溴-苯胺、乙醇胺、N-苄基乙二胺、 2-羟基苄胺、4-氨基苯乙醇、色胺、4-氨基苄胺、吗啉、硫代吗啉、哌啶、四氢吡咯、吲哚啉、四氢异喹啉、1-(2-嘧啶基)哌嗪、N-甲基烯丙基胺、N-甲基苄胺、二苄胺、乙二胺、N-甲基苯胺。
优选地，所述的手性双膦配体为(S)-BIANP、(S)-SegPhos、(S)-SKP、(R)-SDP、(R)-DIOP、(S,S)-BDPP、(RC,SP)-DuanPhos、(S,S)-Me-DuPhos中的任一种，其具体结构如下所示：
Figure BDA0002207447730000031
优选地，所述的
Figure BDA0002207447730000032
酸添加剂为苯甲酸、苯丙酸、苯基磷酸、邻苯二甲酸、对甲苯磺酸、对苯二甲酸、萘乙酸、邻羟基苯甲酸中的任一种，其具体结构如下所示：
Figure BDA0002207447730000033
优选地，所述的有机溶剂为甲醇、乙醇、异丙醇、三氟乙醇、六氟异丙醇、甲苯、三氟甲苯、二氯甲烷、1,2-二氯乙烷、氯仿、乙醚、1,4-二氧六环、四氢呋喃、甲基叔丁基醚、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、 N-甲基吡咯烷酮、乙酸乙酯、乙腈、苄腈、乙二醇二甲醚、正己烷中的一种。
优选地，所述手性烯丙基胺类化合物的制备方法具体步骤如下：在惰性气体中，将金属试剂Ni(COD)2、手性双膦配体溶于干燥的有机溶剂中，然后加入1,3- 共轭二烯、胺以及
Figure BDA0002207447730000035
酸添加剂，得到反应混合物，随后将上述反应混合物密封并从惰性气体中取出，反应完全后，减压浓缩除去有机溶剂，再经柱层析分离纯化得到目标产物手性烯丙基胺类化合物：
Figure BDA0002207447730000034
优选地，金属试剂Ni(COD)2：手性双膦配体：
Figure BDA0002207447730000042
酸添加剂：1,3-共轭二烯：胺：有机溶剂的用量比为0.01mmol：0.01mmol：0.01mmol：0.2mmol： 0.3mmol：1.0mL。
本发明还提供一种手性烯丙基胺类化合物，采用上述的方法制备得到。
与现有技术相比，本发明具有以下优势及特点：
1.本发明公开的合成手性烯丙基胺类化合物的方法，以廉价金属镍 /
Figure BDA0002207447730000043
酸为共催化剂，使用的原料简单易得，操作简便。
2.本发明公开的合成手性烯丙基胺类化合物的方法，反应条件十分温和，在室温下即可进行。
3.本发明公开的合成手性烯丙基胺类化合物的方法，底物范围十分宽广，无论是富电子还是贫电子芳基烯烃底物，杂芳基烯烃甚至烷基取代的烯烃都能很好兼容，无论是一级胺还是二级胺，芳香胺还是脂肪胺都能十分高效地转化，产率高达99％。
4.本发明公开的合成手性烯丙基胺类化合物的方法，具有优异的化学选择性以及立体选择性，对于含有两个亲核位点的胺类底物，能很好地识别反应位点，并且ee值高达99％。
5.本发明公开的合成手性烯丙基胺类化合物的方法，能进行克级规模的放大，并且催化剂负载能降到1％以下。
6.本发明公开的合成手性烯丙基胺类化合物的方法，对于地氯雷他定等药物分子也能高效反应，为药物分子的衍生化及合成复杂药物分子提供了新的方法。
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优势及特点。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，手性化合物的旋光值用Perkin Elmer 343旋光仪测得，ee值通过Agilent 1260Series高效液相色谱仪检测确定，HRMS用Waters Micromass GCT质谱仪检测。
实施例1
Figure BDA0002207447730000041
在充满氩气的手套箱中，将二(1，5-环辛二烯)镍与(S,S)-Me-DuPhos以1:1 的摩尔比混合，溶于干燥的甲苯中，制成浓度为0.01M的溶液(络合一次可开多个反应，按实际需要量制备催化剂溶液)，预搅拌0.5h。随后取该催化剂溶液 1mL，向其中加入1-苯基-1,3-丁二烯(26μL，0.2mmol)，正丁胺(30μL，0.3mmol) 以及邻苯二甲酸(1.7mg，0.01mmol)，将反应小瓶密封并从手套箱中取出，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产物(S,E)-N-butyl-4-phenylbut-3-en-2-amine，无色油状液体，产率93％；ee> 99％；[α]D 25＝-60.3(c＝1.0,CHCl3)；HPLC检测使用Chiralpak AD-H色谱柱,流动相为正己烷：异丙醇(体积比为99:1)，流速为0.6mL/min,检测波长为254nm, 保留时间tR＝9.2min(major),9.7min(minor)；1H NMR(400MHz,CDCl3)δ 7.39-7.36(m,2H),7.33-7.29(m,2H),7.24-7.19(m,1H),6.46(d,J＝15.9Hz,1H), 6.08(dd,J＝15.9,8.0Hz,1H),3.39-3.32(m,1H),2.67-2.53(m,2H),1.52-1.43(m, 2H),1.38-1.29(m,2H),1.25(d,J＝6.5Hz,3H),0.91(t,J＝7.3Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.1,134.4,129.7,128.5,127.2,126.2,56.4,47.3,32.4, 22.0,20.5,14.0ppm；HRMS(ESI)calculated[M+Na]+for C14H21NNa＝226.1566, found:226.1565.
实施例2
Figure BDA0002207447730000051
在充满氩气的手套箱中，将二(1，5-环辛二烯)镍与(S,S)-Me-DuPhos以1:1 的摩尔比混合，溶于干燥的甲苯中，制成浓度为0.01M的溶液(络合一次可开多个反应，按实际需要量制备催化剂溶液)，预搅拌0.5h。随后取该催化剂溶液 1mL，向其中加入1-苯基-1,3-丁二烯(26μL，0.2mmol)，2-苯乙胺(38μL，0.3 mmol)以及邻苯二甲酸(1.7mg，0.01mmol)，将反应小瓶密封并从手套箱中取出，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产物(S,E)-N-phenethyl-4-phenylbut-3-en-2-amine，淡黄色油状液体，产率99％；ee＝92％；[α]D 25＝-76.8(c＝1.0,CHCl3)；HPLC检测使用Chiralpak AD-H色谱柱,流动相为正己烷：异丙醇(体积比为99:1)，流速为0.6mL/min,检测波长为254nm,保留时间tR＝13.9min(major),15.0min(minor)；1H NMR (400MHz,CDCl3)δ7.37-7.34(m,2H),7.32-7.26(m,4H),7.23-7.18(m,4H),6.44 (d,J＝15.9Hz,1H),6.05(dd,J＝15.9,8.0Hz,1H),3.41-3.34(m,1H),2.96-2.79(m, 4H),1.23(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ139.9,136.9, 133.9,129.9,128.7,128.5,128.4,127.3,126.2,126.1,56.2,48.8,36.4,21.9ppm； HRMS(ESI)calculated[M+Na]+for C18H21NNa＝274.1566,found:274.1563.
实施例3
Figure BDA0002207447730000061
在充满氩气的手套箱中，将二(1，5-环辛二烯)镍与(S,S)-Me-DuPhos以1:1 的摩尔比混合，溶于干燥的甲苯中，制成浓度为0.01M的溶液(络合一次可开多个反应，按实际需要量制备催化剂溶液)，预搅拌0.5h。随后取该催化剂溶液 1mL，向其中加入1-苯基-1,3-丁二烯(26μL，0.2mmol)，环丙胺(21μL，0.3mmol) 以及邻苯二甲酸(1.7mg，0.01mmol)，将反应小瓶密封并从手套箱中取出，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产物(S,E)-N-(4-phenylbut-3-en-2-yl)cyclopropanamine，无色油状液体，产率 61％；ee>99％；[α]D 25＝-91.8(c＝1.0,CHCl3)；HPLC检测使用Chiralpak OJ-H 色谱柱,流动相为正己烷：异丙醇(体积比为95:5)，流速为0.5mL/min,检测波长为254nm,保留时间tR＝10.5min(major),10.9min(minor)；1H NMR(400 MHz,CDCl3)δ7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.49(d,J＝ 15.9Hz,1H),6.12(dd,J＝15.9,7.9Hz,1H),3.52-3.45(m,J＝6.7Hz,1H), 2.18-2.13(m,1H),2.02(br,s 1H),1.25(d,J＝6.5Hz,3H),0.47-0.33(m,4H)ppm；13C NMR(100MHz,CDCl3)δ137.2,134.4,129.4,128.5,127.2,126.2,56.5,28.6, 21.8,6.6,6.4ppm；HRMS(ESI)calculated[M+Na]+for C13H17NNa＝210.1253, found:210.1254.
实施例4
Figure BDA0002207447730000062
在充满氩气的手套箱中，将二(1，5-环辛二烯)镍与(S,S)-Me-DuPhos以1:1 的摩尔比混合，溶于干燥的甲苯中，制成浓度为0.01M的溶液(络合一次可开多个反应，按实际需要量制备催化剂溶液)，预搅拌0.5h。随后取该催化剂溶液 1mL，向其中加入1-苯基-1,3-丁二烯(26μL，0.2mmol)，环己胺(34μL，0.3mmol) 以及邻苯二甲酸(1.7mg，0.01mmol)，将反应小瓶密封并从手套箱中取出，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产物(S,E)-N-(4-phenylbut-3-en-2-yl)cyclohexanamine，淡黄色油状液体，产率76％,ee＝91％；[α]D 25＝-66.1(c＝1.0,CHCl3)；HPLC检测使用Chiralpak AD-H色谱柱,流动相为正己烷：异丙醇(体积比为99:1)，流速为0.6mL/min,检测波长为254nm,保留时间tR＝8.7min(major),9.5min(minor)；1H NMR(400 MHz,CDCl3)δ7.49-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.44(d,J＝ 15.9Hz,1H),6.07(dd,J＝15.9,8.1Hz,1H),3.59-3.52(m,1H),2.55-2.48(m,1H), 2.01-1.97(m,1H),1.84-1.58(m,3H),1.69(br,s,1H),1.26-0.98(m,9H)ppm；13C NMR(100MHz,CDCl3)δ137.1,134.8,129.3,128.5,127.2,126.2,53.5,52.5,34.4, 33.2,26.1,25.3,25.0,22.5ppm；HRMS(ESI)calculated[M+Na]+for C16H23NNa＝ 252.1723,found:252.1722.
实施例5
Figure BDA0002207447730000071
在充满氩气的手套箱中，将二(1，5-环辛二烯)镍与(S,S)-Me-DuPhos以1:1 的摩尔比混合，溶于干燥的甲苯中，制成浓度为0.01M的溶液(络合一次可开多个反应，按实际需要量制备催化剂溶液)，预搅拌0.5h。随后取该催化剂溶液 1mL，向其中加入1-苯基-1,3-丁二烯(26μL，0.2mmol)，糠胺(28μL，0.3mmol) 以及邻苯二甲酸(1.7mg，0.01mmol)，将反应小瓶密封并从手套箱中取出，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产物(S,E)-N-(furan-2-ylmethyl)-4-phenylbut-3-en-2-amine，淡黄色油状液体，产率99％；ee＝99％；[α]D 25＝-49.2(c＝1.0,CHCl3)；HPLC检测使用ChiralpakOD-H色谱柱,流动相为正己烷：异丙醇(体积比为99:1)，流速为0.5mL/min,检测波长为254nm,保留时间tR＝17.0min(minor),20.0min(major)；1H NMR(400 MHz,CDCl3)δ7.40-7.36(m,3H),7.33-7.30(m,2H),7.25-7.21(m,1H),6.49(d,J＝ 15.9Hz,1H),6.31(dd,J＝3.1,1.9Hz,1H),6.16(dd,J＝3.1,0.5Hz,1H),6.07(dd,J ＝15.9,8.1Hz,1H),3.83(d,J＝14.4Hz,1H),3.73(d,J＝14.4Hz,1H),3.42-3.35(m, 1H),1.26(d,J＝6.4Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ153.9,141.8, 137.0,133.7,130.5,128.5,127.4,126.3,110.1,106.8,55.3,43.8,22.0ppm；HRMS (ESI)calculated[M+H]+for C15H18NO＝228.1383,found:228.1380.
实施例6克级规模反应
Figure BDA0002207447730000081
在充满氩气的手套箱中，将二(1，5-环辛二烯)镍(13.8mg,0.05mmol)与 (S,S)-Me-DuPhos(15.3mg,0.05mmol)溶于5mL干燥的甲苯中，预搅拌0.5h。随后向该催化剂溶液加入1-苯基-1,3-丁二烯(650μL，5.0mmol)，2-(1-环己烯基)乙胺(1043μL，7.5mmol)以及邻苯二甲酸(41.5mg，0.25mmol)，将反应瓶密封并从手套箱中取出，在25℃下反应96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产物 (S,E)-N-(2-(cyclohex-1-en-1-yl)ethyl)-4-phenylbut-3-en-2-amine 1.23g，为淡黄色油状液体，产率96％；ee＝96％；[α]D 25＝-66.1(c＝1.0,CHCl3)；HPLC检测使用 Chiralpak AD-H色谱柱,流动相为正己烷：异丙醇(体积比为95:5)，流速为0.5 mL/min,检测波长为254nm,保留时间tR＝11.0min(minor),11.6min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H), 6.46(d,J＝15.9Hz,1H),6.07(dd,J＝15.9,8.0Hz,1H),5.48-5.45(m,1H), 3.38-3.31(m,1H),2.74-2.59(m,2H),2.14(t,J＝6.9Hz,2H),2.01-1.97(m,2H), 1.92-1.88(m,2H),1.64-1.51(m,4H),1.46(br,s,1H),1.24(d,J＝6.5Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ137.1,135.4,134.4,129.7,128.5,127.2,126.2,122.8, 56.2,45.2,38.4,28.1,25.2,22.9,22.4,22.1ppm；HRMS(ESI)calculated[M+H]+ for C18H26N＝256.2060,found:256.2057.
以下实施例7-实施例50均以上述实施例1-实施例5的方法步骤进行，合成得到的化合物结构及数据表征如下：
实施例7
(S,E)-N-allyl-4-phenylbut-3-en-2-amine:淡黄色油状液体，产率
Figure BDA0002207447730000091
＝11.9min(major),12.7min(minor)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m, 2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.46(d,J＝15.9Hz,1H),6.06(dd,J＝ 15.9,8.1Hz,1H),5.97-5.87(m,1H),5.20-5.15(m,1H),5.12-5.08(m,1H),3.44-3.36 (m,1H),3.34-3.28(m,1H),3.24-3.18(m,1H),1.86(br,s,1H),1.26(d,J＝6.5Hz, 3H)ppm；13C NMR(100MHz,CDCl3)δ137.0,136.8,133.9,130.1,128.5,127.3, 126.2,115.9,55.6,50.0,22.0ppm；HRMS(ESI)calculated[M+Na]+for C13H17NNa ＝210.1253,found:210.1258.
实施例8
(2S,E)-4-phenyl-N-((tetrahydrofuran-2-yl)methyl)but-3-en-2-a
Figure BDA0002207447730000092
检测波长为254nm,保留时间tR1＝15.3min(major),16.9min (minor),tR2＝19.8min(minor),21.2min(major)；3i:1H NMR(400MHz,CDCl3)δ 7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.50(d,J＝5.7Hz,1H), 6.08(dd,J＝8.1,3.2Hz,1H),4.08-3.98(m,1H),3.88-3.82(m,1H),3.78-3.72(m, 1H),3.45-3.38(m,1H),2.77(dd,J＝11.9,3.4Hz,1H),2.68(d,J＝1.9Hz,1H), 2.02-1.84(m,3H),1.58-1.46(m,1H),1.29(d,J＝3.3Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ136.9,133.7,130.4,128.5,127.3,126.3,78.5,67.9,56.8,52.3,29.4, 25.7,21.9ppm；3i′:1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.46(d,J＝5.7Hz,1H),6.12(dd,J＝8.1,3.2Hz,1H), 4.08-3.98(m,1H),3.88-3.82(m,1H),3.78-3.72(m,1H),3.45-3.38(m,1H),2.70(s, 1H),2.58(dd,J＝11.9,8.5Hz,1H),2.02-1.84(m,3H),1.58-1.46(m,1H),1.27(d,J ＝3.3Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ136.9,133.7,130.2,128.5,127.3, 126.3,77.9,67.9,56.2,51.7,29.3,25.7,21.8ppm；HRMS(ESI)calculated[M+H]+ for C15H22NO＝232.1696,found:232.1693.
实施例9
(S,E)-N1,N1-dimethyl-N2-(4-phenylbut-3-en-2-yl)ethane-1,2-dia
Figure BDA0002207447730000101
90:10)，流速为0.5mL/min,检测波长为254nm,保留时间tR＝ 43.1min(major),50.8min(minor)；1HNMR(400MHz,CDCl3)δ7.39-7.37(m,2H), 7.32-7.29(m,2H),7.24-7.20(m,1H),6.47(d,J＝15.9Hz,1H),6.08(dd,J＝15.9, 8.0Hz,1H),3.39-3.32(m,1H),2.78-2.62(m,2H),2.46-2.43(m,3H),2.22(s,6H), 1.27(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.0,134.0,130.0, 128.5,127.3,126.2,59.0,56.5,45.4,44.7,22.0ppm；HRMS(ESI)calculated [M+H]+for C14H23N2＝219.1856,found:219.1856.
实施例10
(S,E)-N-benzyl-4-phenylbut-3-en-2-amine:淡黄色油状液体，产率91％；ee＝90％；
Figure BDA0002207447730000102
12.5min(minor)；1H NMR(400MHz,CDCl3)δ7.40-7.38(m,2H),7.33-7.30(m, 6H),7.27-7.20(m,2H),6.48(d,J＝15.9Hz,1H),6.11(dd,J＝15.9,8.0Hz,1H), 3.85(d,J＝13.1Hz,1H)3.73(d,J＝13.1Hz,1H),3.44-3.37(m,1H),1.27(d,J＝ 6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ140.5,137.1,134.2,130.1,128.5, 128.4,128.1,127.3,126.9,126.3,55.5,51.5,22.1ppm；HRMS(ESI)calculated [M+Na]+for C17H19NNa＝260.1410,found:260.1405.
实施例11
methyl(S,E)-(4-phenylbut-3-en-2-yl)glycinate:淡黄色油状液体，产率80％；ee>
Figure BDA0002207447730000103
速为0.5mL/min,检测波长为254nm,保留时间tR＝27.2min(major),28.4min (minor)；1H NMR(400MHz,CDCl3)δ7.38-7.35(m,2H),7.32-7.29(m,2H), 7.24-7.20(m,1H),6.45(d,J＝15.8Hz,1H),6.01(dd,J＝15.8,8.2Hz,1H),3.69(s, 3H),3.42(d,J＝3.1Hz,2H),3.39-3.32(m,1H),2.17(br,s,1H),1.27(d,J＝6.5Hz, 3H)ppm；13C NMR(100MHz,CDCl3)δ173.2,136.8,133.2,130.7,128.5,127.5, 126.3,56.2,51.8,48.4,22.0ppm；HRMS(ESI)calculated[M+H]+for C13H18NO2＝ 220.1332,found:220.1331.
实施例12
(S,E)-4-phenyl-N-((R)-1-phenylethyl)but-3-en-2-amine:淡黄色油状液体，产率
Figure BDA0002207447730000111
3.38-3.31(m,1H),1.76(br,s,1H),1.37(d,J＝6.6Hz,3H),1.22(d,J＝6.4Hz,3H) ppm；13CNMR(100MHz,CDCl3)δ145.8,137.1,134.6,129.2,128.5,127.2,126.8, 126.5,126.2,54.8,53.0,23.7,21.2ppm；HRMS(ESI)calculated[M+Na]+for C18H21NNa＝274.1566,found:274.1566.
实施例13
(S,E)-N-(4-phenylbut-3-en-2-yl)aniline:淡黄色油状液体，产时间tR＝11.6min(major),13.4min(minor)；1H NMR(400MHz,CDCl3)δ 7.36-7.34(m,2H),7.30-7.27(m,2H),7.22-7.13(m,3H),6.70-6.63(m,3H),6.57(d, J＝16.0Hz,1H),6.21(dd,J＝16.0,5.8Hz,1H),4.17-4.11(m,1H),1.40(d,J＝6.6 Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ147.4,136.9,133.2,129.2,129.1, 128.5,127.3,126.3,117.3,113.4,50.8,22.1ppm；HRMS(ESI)calculated[M+Na]+ for C16H17NNa＝246.1253,found:246.1253.
实施例14
(S,E)-4-methyl-N-(4-phenylbut-3-en-2-yl)aniline:红褐色油状液体，产率23％；ee
Figure BDA0002207447730000113
＝93％；[α]D 25＝-99.5(c＝1.0,CHCl3)；HPLC检测使用Chiralpak AD-H色谱柱,流动相为正己烷：异丙醇(体积比为95:5)，流速为0.5mL/min,检测波长为254 nm,保留时间tR＝14.6min(major),16.5min(minor)；1H NMR(400MHz,CDCl3) δ7.36-7.34(m,2H),7.31-7.27(m,2H),7.22-7.18(m,1H),6.97(d,J＝8.2Hz,2H), 6.59-6.55(m,3H),6.21(dd,J＝16.0,5.9Hz,1H),4.14-4.08(m,1H),2.22(s,3H), 1.39(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ145.1,136.9,133.4, 129.6,129.1,128.5,127.3,126.5,126.3,113.6,51.1,22.1,20.4ppm；HRMS(ESI) calculated[M+Na]+for C17H19NNa＝260.1410,found:260.1405.
实施例15
(S,E)-4-bromo-N-(4-phenylbut-3-en-2-yl)aniline:红褐色油状液体，产率48％；ee
Figure BDA0002207447730000121
时间tR＝13.5min(minor),17.2min(major)；1H NMR(400MHz,CDCl3)δ 7.35-7.32(m,2H),7.31-7.27(m,2H),7.24-7.19(m,3H),6.56-6.49(m,3H),6.16(dd, J＝16.0,5.8Hz,1H),4.12-4.05(m,1H),3.75(br,s,1H),1.40(d,J＝6.7Hz,3H) ppm；13C NMR(100MHz,CDCl3)δ146.3,136.7,132.5,131.8,129.5,128.5,127.5, 126.3,114.9,108.8,50.9,22.0ppm；HRMS(ESI)calculated[M+H]+for C16H17BrN ＝302.0539,found:302.0524.
实施例16
(S,E)-4-(4-phenylbut-3-en-2-yl)morpholine:淡黄色油状液体，产率99％；ee＝(minor),14.4min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H), 7.33-7.29(m,2H),7.25-7.21(m,1H),6.47(d,J＝15.9Hz,1H),6.17(dd,J＝15.9, 8.2Hz,1H),3.73(t,J＝4.7Hz,4H),3.05-2.99(m,1H),2.61-2.52(m,4H),1.26(d,J ＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.8,132.0,131.2,128.6,127.5, 126.2,67.2,63.1,50.8,17.8ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNaO＝240.1359,found:240.1359.
实施例17
(S,E)-4-(4-phenylbut-3-en-2-yl)thiomorpholine:无色油状液体，
Figure BDA0002207447730000131
tR＝8.7min(minor),9.7min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m, 2H),7.33-7.30(m,2H),7.25-7.21(m,1H),6.44(d,J＝16.0Hz,1H),6.21(dd,J＝ 16.0,7.2Hz,1H),3.27-3.20(m,1H),2.90-2.80(m,4H),2.69(t,J＝5.0Hz,4H),1.25 (d,J＝6.7Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.9,131.7,130.9,128.5, 127.4,126.2,62.7,51.6,28.3,16.3ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNaS＝256.1130,found:256.1130.
实施例18
(S,E)-1-(4-phenylbut-3-en-2-yl)piperidine:淡黄色油状液体，产
Figure BDA0002207447730000132
8.6min(minor),9.8min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H), 7.32-7.29(m,2H),7.24-7.19(m,1H),6.43(d,J＝16.0Hz,1H),6.24(dd,J＝15.9, 8.0Hz,1H),3.11-3.05(m,1H),2.52-2.50(m,4H),1.63-1.57(m,4H),1.46-1.42(m, 2H),1.26(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ137.2,132.7, 130.5,128.5,127.2,126.2,63.0,51.0,26.2,24.6,17.7ppm；HRMS(ESI)calculated [M+Na]+for C15H21NNa＝238.1566,found:238.1568.
实施例19
(S,E)-1-(4-phenylbut-3-en-2-yl)pyrrolidine:淡黄色油状液体，产率91％；ee＝
Figure BDA0002207447730000133
(minor),8.1min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m,2H),7.32-7.29 (m,2H),7.24-7.20(m,1H),6.47(d,J＝15.9Hz,1H),6.24(dd,J＝15.8,8.6Hz,1H), 2.93-2.86(m,1H),2.61-2.55(m,4H),1.81-1.78(m,4H),1.30(d,J＝6.5Hz,3H) ppm；13C NMR(100MHz,CDCl3)δ137.1,133.9,129.6,128.5,127.2,126.2,63.1, 52.2,23.3,21.0ppm；HRMS(ESI)calculated[M+Na]+for C14H19NNa＝224.1410, found:224.1410.
实施例20
(S,E)-1-(4-phenylbut-3-en-2-yl)indoline:淡黄色油状液体，产率87％；ee＝97％；
Figure BDA0002207447730000141
14.6min(minor)；1H NMR(400MHz,CDCl3)δ7.37-7.34(m,2H),7.31-7.27(m, 2H),7.23-7.19(m,1H),7.07-7.02(m,2H),6.64-6.60(m,1H),6.57-6.52(m,2H), 6.32(dd,J＝16.1,5.6Hz,1H),4.39-4.33(m,1H),3.46-3.36(m,2H),2.95(t,J＝8.4 Hz,2H),1.40(d,J＝6.9Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ151.0,136.9, 130.7,130.4,130.3,128.5,127.4,127.2,126.3,124.4,117.2,107.6,52.2,47.3,28.2, 16.1ppm；HRMS(ESI)calculated[M+Na]+for C18H19NNa＝272.1410,found: 272.1412.
实施例21
(S,E)-2-(4-phenylbut-3-en-2-yl)-1,2,3,4-tetrahydroisoquinoline:淡黄色油状液体，CDCl3)δ7.41-7.39(m,2H),7.34-7.30(m,2H),7.24-7.22(m,1H),7.12-7.07(m,3H), 7.03-7.01(m,1H),6.53(d,J＝16.0Hz,1H),6.30(dd,J＝16.0,7.9Hz,1H), 3.83-3.74(m,2H),3.34-3.27(m,1H),2.97-2.90(m,3H),2.84-2.73(m,1H),1.37(d, J＝6.6Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ137.0,134.9,134.4,132.3, 130.9,128.6,128.5,127.4,126.8,126.3,126.0,125.5,61.9,53.0,47.3,29.4,17.9 ppm；HRMS(ESI)calculated[M+Na]+forC19H21NNa＝286.1566,found:286.1563.
实施例22
Figure BDA0002207447730000143
黄色油状液体，产率99％；ee＝95％；[α]D 25＝-68.1(c＝1.0,CHCl3)；HPLC检测使用Chiralpak AD-H色谱柱,流动相为正己烷：异丙醇(体积比为95:5)，流速为0.5mL/min,检测波长为254nm,保留时间tR＝12.7min(major),15.2min (minor)；1H NMR(400MHz,CDCl3)δ8.29(d,J＝4.7Hz,2H),7.39-7.36(m,2H), 7.33-7.29(m,2H),7.25-7.20(m,1H),6.49-6.45(m,2H),6.22(dd,J＝15.9,8.0Hz, 1H),3.85(t,J＝5.2Hz,4H),3.17-3.10(m,1H),2.69-2.59(m,4H),1.30(d,J＝6.6 Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ161.6,157.7,136.9,132.0,131.2, 128.6,127.4,126.3,109.8,62.6,49.9,43.9,17.8ppm；HRMS(ESI)calculated [M+Na]+for C18H22N4Na＝317.1737,found:317.1730.
实施例23
(S,E)-N-allyl-N-methyl-4-phenylbut-3-en-2-amine:淡黄色油状
Figure BDA0002207447730000151
间tR＝8.0min(minor),9.3min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.36(m, 2H),7.33-7.28(m,2H),7.24-7.20(m,1H),6.45(d,J＝16.0Hz,1H),6.22(dd,J＝ 16.0,7.6Hz,1H),5.93-5.83(m,1H),5.20-5.11(m,2H),3.34-3.27(m,1H),3.19-3.13 (m,1H),3.09-3.03(m,1H),2.25(s,3H),1.25(d,J＝6.7Hz,3H)ppm；13C NMR (100MHz,CDCl3)δ137.2,136.3,131.9,130.8,128.5,127.3,126.3,117.3,60.4,57.4, 37.7,17.2ppm；HRMS(ESI)calculated[M+Na]+forC14H19NNa＝224.1410,found: 224.1412.
实施例24
(S,E)-N-benzyl-N-methyl-4-phenylbut-3-en-2-amine:淡黄色油状液体，产率88％；
Figure BDA0002207447730000152
5.0min(minor),6.0min(major)；1H NMR(400MHz,CDCl3)δ7.41-7.39(m,2H), 7.36-7.30(m,6H),7.26-7.21(m,2H),6.47(d,J＝16.1Hz,1H),6.31(dd,J＝16.0, 7.3Hz,1H),3.65(d,J＝13.2Hz,1H),3.51(d,J＝13.2Hz,1H),3.39-3.32(m,1H), 2.22(s,3H),1.30(d,J＝6.7Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ139.8, 137.2,132.0,130.8,128.9,128.5,128.2,127.3,126.8,126.2,60.4,58.2,37.9,16.9 ppm；HRMS(ESI)calculated[M+Na]+forC18H21NNa＝274.1566,found:274.1563.
实施例25
(S,E)-N,N-dibenzyl-4-phenylbut-3-en-2-amine:淡黄色油状液体，产率53％；ee＝
Figure BDA0002207447730000161
(major),10.5min(minor)；1H NMR(400MHz,CDCl3)δ7.42-7.38(m,6H), 7.34-7.29(m,6H),7.24-7.20(m,3H),6.43(d,J＝16.2Hz,1H),6.32(dd,J＝16.1, 6.6Hz,1H),3.71(d,J＝13.9Hz,2H),3.59(d,J＝13.9Hz,2H),3.51-3.44(m,1H), 1.29(d,J＝6.8Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ140.6,137.3,131.6, 130.9,128.52,128.50,128.2,127.2,126.7,126.2,54.8,53.7,15.8ppm；HRMS(ESI) calculated[M+Na]+for C24H25NNa＝350.1879,found:350.1873.
实施例26
(S,E)-N,N-diethyl-4-phenylbut-3-en-2-amine:淡黄色油状液
Figure BDA0002207447730000162
保留时间tR＝7.7min(minor),8.0min(major)；1H NMR(400MHz,CDCl3)δ7.39-7.37(m,2H),7.33-7.29(m,2H),7.24-7.20(m,1H),6.44(d,J＝16.0Hz,1H), 6.24(dd,J＝16.0,7.5Hz,1H),3.50-3.43(m,1H),2.69-2.53(m,4H),1.24(d,J＝6.6 Hz,3H),1.06(t,J＝7.2Hz,6H)ppm；13C NMR(100MHz,CDCl3)δ137.2,133.0, 130.0,128.5,127.2,126.2,57.5,43.4,17.4,12.8ppm；HRMS(ESI)calculated [M+Na]+for C14H21NNa＝226.1566,found:226.1568.
实施例27
(S,E)-N-methyl-N-(4-phenylbut-3-en-2-yl)aniline:淡黄色油状液体，产率22％；ee
Figure BDA0002207447730000163
95:5)，流速为1.0mL/min,检测波长为254nm,保留时间tR＝11.7min(major), 15.0min(minor)；1H NMR(400MHz,CDCl3)δ7.38-7.35(m,2H),7.32-7.20(m, 5H),6.86-6.83(m,2H),6.75-6.71(m,1H),6.48(dd,J＝16.2,1.9Hz,1H),6.30(dd, J＝16.2,4.4Hz,1H),4.69-4.62(m,1H),2.79(s,3H),1.37(d,J＝6.8Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ150.0,137.1,131.3,130.0,129.2,128.6,127.4,126.3, 116.8,113.4,54.9,31.7,16.2ppm；HRMS(ESI)calculated[M+Na]+for C17H19NNa ＝260.1410,found:260.1411.
实施例28
(S,E)-N-(furan-2-ylmethyl)-4-(2-methoxyphenyl)but-3-en-2-amine:淡黄色油状
Figure BDA0002207447730000171
(dd,J＝1.9,0.9Hz,1H),7.23-7.19(m,1H),6.94-6.90(m,1H),6.87(dd,J＝8.2,1.1 Hz,1H),6.81(d,J＝16.0Hz,1H),6.31(dd,J＝3.2,1.8Hz,1H),6.17(dd,J＝3.2, 0.8Hz,1H),6.07(dd,J＝16.0,8.2Hz,1H),3.85(s,3H),3.83(d,J＝14.7Hz,1H), 3.74(d,J＝14.4Hz,1H),3.43-3.36(m,1H),1.26(d,J＝6.4Hz,3H)ppm；13C NMR (100MHz,CDCl3)δ156.6,154.1,141.7,134.3,128.4,126.7,126.0,125.2,120.6, 110.8,110.0,106.8,55.7,55.4,43.8,22.1ppm；HRMS(ESI)calculated[M+H]+for C16H20NO2＝258.1489,found:258.1484.
实施例29
(S,E)-N-(furan-2-ylmethyl)-4-(4-methoxyphenyl)but-3-en-2-amine:淡黄色油状
Figure BDA0002207447730000172
J＝2.0,0.8Hz,1H),7.34-7.30(m,2H),6.88-6.84(m,2H),6.43(d,J＝15.9Hz,1H), 6.31(dd,J＝3.2,1.8Hz,1H),6.16(dd,J＝3.1,0.8Hz,1H),5.93(dd,J＝15.8,8.2 Hz,1H),3.83(d,J＝13.2Hz,1H),3.81(s,3H),3.73(d,J＝14.4Hz,1H),3.39-3.33 (m,1H),1.86(br,s,1H),1.25(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3) δ159.0,153.9,141.8,131.4,130.0,129.7,127.4,113.9,110.1,106.8,55.33,55.29, 43.8,22.1ppm；HRMS(ESI)calculated[M+Na]+for C16H19NNaO2＝280.1308, found:280.1310.
实施例30
(S,E)-4-(4-fluorophenyl)-N-(furan-2-ylmethyl)but-3-en-2-amine:淡黄色油状液(m,2H),6.45(d,J＝15.8Hz,1H),6.31(dd,J＝3.1,1.9Hz,1H),6.16(dd,J＝3.2, 0.8Hz,1H),5.99(dd,J＝15.8,8.1Hz,1H),3.82(d,J＝14.4Hz,1H),3.73(d,J＝ 14.4Hz,1H),3.41-3.34(m,1H),1.83(br,s,1H),1.25(d,J＝6.4Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ162.1(d,J＝246.5Hz),153.8,141.8,133.4(d,J＝2.2 Hz),133.1(d,J＝3.2Hz),129.3,127.7(d,J＝7.9Hz),115.4(d,J＝21.4Hz),110.1, 106.8,55.2,43.8,22.0ppm；19F NMR(376MHz,CDCl3)δ-114.82ppm；HRMS (ESI)calculated[M+Na]+for C15H16FNNaO＝268.1108,found:268.1103.
实施例31
(S,E)-N-(furan-2-ylmethyl)-4-(4-(trifluoromethyl)phenyl)but-3-en-2-amine:淡黄
Figure BDA0002207447730000182
Hz,2H),7.46(d,J＝8.2Hz,2H),7.37(dd,J＝1.9,0.8Hz,1H),6.52(d,J＝15.9Hz, 1H),6.31(dd,J＝3.2,1.8Hz,1H),6.21-6.15(m,2H),3.82(d,J＝14.5Hz,1H),3.74 (d,J＝14.5Hz,1H),3.45-3.38(m,1H),1.82(br,s,1H),1.27(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ153.7,141.8,140.5(q,J＝1.6Hz),136.5,129.11(q, J＝32.2Hz),129.09,126.4,125.5(q,J＝3.9Hz),124.2(q,J＝270.5Hz),110.1, 106.9,55.1,43.8,21.8ppm；19F NMR(376MHz,CDCl3)δ-62.36ppm；HRMS (ESI)calculated[M+H]+for C16H17F3NO＝296.1257,found:296.1250.
实施例32
(S,E)-4-(3-((furan-2-ylmethyl)amino)but-1-en-1-yl)-N,N-dimethylaniline:淡黄色δ7.36(dd,J＝1.9,0.8Hz,1H),7.29-7.27(m,2H),6.70-6.67(m,2H),6.39(d,J＝ 15.8Hz,1H),6.31(dd,J＝3.2,1.9Hz,1H),6.16(dd,J＝3.1,0.8Hz,1H),5.85(dd, J＝15.8,8.2Hz,1H),3.83(d,J＝14.4Hz,1H),3.73(d,J＝14.4Hz,1H),3.38-3.31 (m,1H),2.95(s,6H),2.24(br,s,1H),1.25(d,J＝6.4Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ153.9,150.0,141.7,130.6,129.1,127.2,125.4,112.5,110.0,106.8, 55.5,43.6,40.6,22.1ppm；HRMS(ESI)calculated[M+H]+for C17H23N2O＝ 271.1805,found:271.1805.
实施例33
(S,E)-4-(furan-2-yl)-N-(furan-2-ylmethyl)but-3-en-2-amine:淡黄色油状液体，产
Figure BDA0002207447730000192
MHz,CDCl3)δ7.36(dd,J＝1.9,0.9Hz,1H),7.34(d,J＝1.8Hz,1H),6.36(dd,J＝3.3,1.8Hz,1H),6.34-6.30(m,2H),6.21(d,J＝3.2Hz,1H),6.16(dd,J＝3.2,0.8Hz, 1H),6.02(dd,J＝15.8,8.0Hz,1H),3.82(d,J＝14.5Hz,1H),3.72(d,J＝14.4Hz, 1H),3.37-3.30(m,1H),1.24(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 154.0,152.6,141.8,141.7,132.5,118.9,111.2,110.1,107.2,106.8,54.9,43.8,22.0 ppm；HRMS(ESI)calculated[M+H]+forC13H16NO2＝218.1176,found:218.1177.
实施例34
(S,E)-4-cyclohexyl-N-(furan-2-ylmethyl)but-3-en-2-amine:淡黄色油状液体，产1H),6.13(dd,J＝3.1,0.9Hz,1H),5.48(dd,J＝15.4,6.6Hz,1H),5.24-5.18m,1H), 3.77(d,J＝14.5Hz,1H),3.67(d,J＝14.4Hz,1H),3.16-3.09(m,1H),1.99-1.90(m, 1H),1.74-1.69(m,4H),1.67-1.64(m,1H),1.29-1.16(m,3H),1.14(d,J＝6.4Hz, 3H),1.11-1.02(m,2H)ppm；13C NMR(100MHz,CDCl3)δ154.2,141.6,137.9, 130.9,110.0,106.6,55.1,43.6,40.4,33.1,33.0,26.2,26.0,22.1ppm；HRMS(ESI) calculated[M+H]+for C15H24NO＝234.1852,found:234.1853.
实施例35
(S,E)-4-(4-(2-methoxyphenyl)but-3-en-2-yl)morpholine:淡黄色油状液体，产率
Figure BDA0002207447730000202
CDCl3)δ7.44(dd,J＝7.6,1.7Hz,1H),7.23-7.19(m,1H),6.93-6.89(m,1H),6.86 (dd,J＝8.2,1.2Hz,1H),6.79(d,J＝16.0Hz,1H),6.17(dd,J＝16.0,8.3Hz,1H), 3.84(s,3H),3.73(t,J＝4.7Hz,4H),3.07-2.99(m,1H),2.62-2.52(m,4H),1.26(d,J ＝6.6Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ156.5,132.5,128.5,126.6,125.9, 125.8,120.6,110.9,67.2,63.6,55.4,50.8,17.9ppm；HRMS(ESI)calculated [M+H]+for C15H22NO2＝248.1645,found:248.1641.
实施例36
(S,E)-4-(4-(furan-2-yl)but-3-en-2-yl)morpholine:淡黄色油状液体，产率99％；ee
Figure BDA0002207447730000203
间tR＝16.6min(minor),18.7min(major)；1H NMR(400MHz,CDCl3)δ7.33(d,J ＝1.8Hz,1H),6.36(dd,J＝3.3,1.8Hz,1H),6.31-6.27(m,1H),6.20(d,J＝3.3Hz, 1H),6.11(dd,J＝15.9,8.1Hz,1H),3.72(t,J＝4.7Hz,4H),3.04-2.97(m,1H), 2.60-2.50(m,4H),1.23(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 152.5,141.7,130.7,119.7,111.2,107.3,67.2,62.7,50.5,17.5ppm；HRMS(ESI) calculated[M+H]+for C12H18NO2＝208.1332,found:208.1333.
实施例37
(S,E)-4-(4-(4-methoxyphenyl)but-3-en-2-yl)morpholine:
Figure BDA0002207447730000211
(minor),29.0min(major)；1H NMR(400MHz,CDCl3)δ7.31(d,J＝8.7Hz,2H), 6.85(d,J＝8.7Hz,2H),6.41(d,J＝15.9Hz,1H),6.02(dd,J＝15.9,8.3Hz,1H), 3.81(s,3H),3.74(t,J＝4.7Hz,4H),3.03-2.96(m,1H),2.61-2.53(m,4H),1.26(d,J ＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ159.1,130.8,129.6,129.5,127.4, 113.9,67.10,63.2,55.3,50.7,17.8ppm；HRMS(ESI)calculated[M+Na]+for C15H21NNaO2＝270.1465,found:270.1464.
实施例38
(S,E)-4-(4-(4-fluorophenyl)but-3-en-2-yl)morpholine:淡
Figure BDA0002207447730000212
(major)；1H NMR(400MHz,CDCl3)δ7.36-7.31(m,2H),7.03-6.97(m,2H),6.43(d, J＝15.9Hz,1H),6.08(dd,J＝15.9,8.2Hz,1H),3.74(t,J＝4.7Hz,4H),3.04-2.97 (m,1H),2.58-2.54(m,4H),1.25(d,J＝6.6Hz,3H)ppm；13C NMR(100MHz, CDCl3)δ162.2(d,J＝246.6Hz),133.0(d,J＝3.3Hz),131.8(d,J＝2.1Hz),130.0, 127.7(d,J＝7.9Hz),115.4(d,J＝21.6Hz),67.2,63.0,50.7,17.7ppm；19F NMR (376MHz,CDCl3)δ-114.64ppm；HRMS(ESI)calculated[M+H]+for C14H19FNO ＝236.1445,found:236.1442.
实施例39
(S,E)-4-(4-(4-(trifluoromethyl)phenyl)but-3-en-2-yl)morpholine:淡黄色油状液
Figure BDA0002207447730000221
(minor)；1H NMR(400MHz,CDCl3)δ7.56(d,J＝8.2Hz,2H),7.46(d,J＝8.4Hz, 2H),6.50(d,J＝16.0Hz,1H),6.28(dd,J＝16.0,8.0Hz,1H),3.75-3.72(m,4H), 3.10-3.02(m,1H),2.58-2.55(m,4H),1.27(d,J＝6.6Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ140.3(q,J＝1.9Hz),135.0,129.9,129.2(q,J＝32.4Hz),126.4, 125.5(q,J＝3.8Hz),124.1(q,J＝270.9Hz),67.1,62.9,50.7,17.5ppm；19F NMR (376MHz,CDCl3)δ-62.38ppm；HRMS(ESI)calculated[M+H]+for C15H19F3NO＝ 286.1413,found:286.1418.
实施例40
(S,E)-N,N-dimethyl-4-(3-morpholinobut-1-en-1-yl)aniline:淡黄色油状液体，产
Figure BDA0002207447730000222
(minor)；1H NMR(400MHz,CDCl3)δ7.28-7.25(m,2H),6.69-6.67(m,2H),6.37(d, J＝15.8Hz,1H),5.94(dd,J＝15.9,8.3Hz,1H),3.73(t,J＝4.7Hz,4H),3.00-2.97 (m,1H),2.95(s,6H),2.61-2.52(m,4H),1.25(d,J＝6.5Hz,3H)ppm；13C NMR (100MHz,CDCl3)δ150.0,131.2,127.5,127.1,125.4,112.5,67.2,63.4,50.8,40.6, 18.0ppm；HRMS(ESI)calculated[M+H]+for C16H25N2O＝261.1961,found: 261.1960.
实施例41
Figure BDA0002207447730000223
无色油状液体，产率58％；ee＝96％；[α]D 25＝-17.7(c＝1.0,CHCl3)；HPLC检测使用Chiralpak OJ-H色谱柱,流动相为正己烷：异丙醇(体积比为95:5)，流速为0.5mL/min,检测波长为254nm,保留时间tR＝8.8min(minor),9.5min(major)；1H NMR(400MHz,CDCl3)δ8.29(d,J＝4.7Hz,2H),6.46(t,J＝4.7Hz,1H),5.47 (dd,J＝15.6,6.4Hz,1H),5.37-5.31(m,1H),3.83-3.81(m,4H),2.93-2.86(m,1H), 2.62-2.49(m,4H),1.99-1.90(m,1H),1.72-1.69(m,4H),1.66-1.62(m,1H), 1.28-1.22(m,3H),1.18(d,J＝6.6Hz,3H),1.14-1.02(m,2H)ppm；13C NMR(100 MHz,CDCl3)δ161.6,157.7,138.5,128.7,109.6,62.5,49.6,43.8,40.4,33.04,32.97, 26.1,26.0,18.1ppm；HRMS(ESI)calculated[M+H]+for C18H29N4＝301.2387, found:301.2380.
实施例42
(S,E)-2-((4-phenylbut-3-en-2-yl)amino)ethan-1-ol:淡黄色油状液体，产率91％；
Figure BDA0002207447730000231
254nm,保留时间tR＝20.0min(major),24.7min(minor)；1H NMR(400MHz, CDCl3)δ7.39-7.37(m,2H),7.32-7.29(m,2H),7.25-7.21(m,1H),6.50(d,J＝15.9 Hz,1H),6.12(dd,J＝15.9,8.1Hz,1H),3.76-3.67(m,2H),3.53-3.41(m,1H),3.41 (br,s,1H),3.32(br,s,1H),2.93-2.79(m,2H),1.35(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ136.4,131.6,131.5,128.5,127.7,126.4,60.3,56.3,48.5, 21.2ppm；HRMS(ESI)calculated[M+H]+forC12H18NO＝192.1383,found: 192.1381.
实施例43
(S,E)-N1-benzyl-N1-(4-phenylbut-3-en-2-yl)ethane-1,2-diami
Figure BDA0002207447730000232
为85:15)，流速为1.0mL/min,检测波长为254nm,保留时间tR＝24.4min (minor),27.6min(major)；1HNMR(400MHz,CDCl3)δ7.37-7.35(m,2H), 7.32-7.28(m,6H),7.25-7.19(m,2H),6.44(d,J＝15.9Hz,1H),6.05(dd,J＝15.9, 7.9Hz,1H),3.79(s,2H),3.35-3.28(m,1H),2.81-2.65(m,4H),1.25(br,s,2H),1.25 (d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ140.3,137.0,134.2,129.9, 128.5,128.4,128.1,127.3,126.9,126.3,56.3,53.8,48.8,46.9,22.0ppm；HRMS (ESI)calculated[M+H]+for C19H25N2＝281.2012,found:282.2011.
实施例44
(S,E)-2-(((4-phenylbut-3-en-2-yl)amino)methyl)phenol:淡黄色油状液体，产率
Figure BDA0002207447730000241
δ7.39-7.31(m,4H),7.27-7.23(m,1H),7.19-7.14(m,1H),6.96(dd,J＝7.4,1.7Hz, 1H),6.85(dd,J＝8.1,1.2Hz,1H),6.79-6.75(m,1H),6.46(d,J＝15.9Hz,1H),6.03 (dd,J＝15.9,8.2Hz,1H),4.08(d,J＝14.0Hz,1H),3.91(d,J＝13.9Hz,1H), 3.46-3.38(m,1H),1.32(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ 158.2,136.5,131.7,131.5,128.6,128.6,128.3,127.7,126.3,122.7,119.1,116.4, 55.1,50.0,21.7ppm；HRMS(ESI)calculated[M+Na]+for C17H19NO＝276.1359, found:276.1361.
实施例45
(S,E)-2-(2-((4-phenylbut-3-en-2-yl)amino)phenyl)ethan-1-ol:白色固体，产率59％；
Figure BDA0002207447730000242
MHz,CDCl3)δ7.37-7.34(m,2H),7.31-7.27(m,2H),7.23-7.19(m,1H),7.03-7.00 (m,2H),6.63-6.60(m,2H),6.57(dd,J＝15.9,1.3Hz,1H),6.20(dd,J＝15.9,5.9Hz, 1H),4.15-4.08(m,1H),3.78(t,J＝6.5Hz,2H),2.74(t,J＝6.5Hz,2H),1.40(d,J＝ 6.6Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ146.0,136.9,133.2,129.8,129.2, 128.5,127.3,126.7,126.3,113.6,63.9,51.0,38.2,22.1ppm；HRMS(ESI) calculated[M+Na]+for C18H21NNaO＝290.1532,found:290.1531.
实施例46
(S,E)-N-(2-(1H-indol-3-yl)ethyl)-4-phenylbut-3-en-2-amine:淡
Figure BDA0002207447730000251
NMR(400MHz,CDCl3)δ8.12(s,1H),7.62(d,J＝7.9Hz,1H), 7.37-7.27(m,5H),7.23-7.17(m,2H),7.10(t,J＝7.5Hz,1H),7.04(d,J＝2.3Hz, 1H),6.42(d,J＝15.9Hz,1H),6.06(dd,J＝15.9,8.0Hz,1H),3.41-3.34(m,1H), 3.04-2.92(m,4H),1.97(br,s,1H),1.22(d,J＝6.4Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ137.0,136.4,134.1,129.9,128.5,127.4,127.3,126.2,122.02,121.98, 119.2,118.9,113.8,111.1,56.2,47.4,25.8,22.0ppm；HRMS(ESI)calculated [M+Na]+for C20H22N2Na＝313.1675,found:313.1675.
实施例47
(S,E)-4-(((4-phenylbut-3-en-2-yl)amino)methyl)aniline:淡黄色油状液体，产率
Figure BDA0002207447730000252
7.12-7.09(m,2H),6.67-6.63(m,2H),6.47(d,J＝15.9Hz,1H),6.11(dd,J＝15.9, 8.0Hz,1H),3.73(d,J＝12.8Hz,1H),3.61(d,J＝12.9Hz,1H),3.43-3.36(m,1H), 1.25(d,J＝6.5Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ145.2,137.1,134.2, 130.4,130.1,129.3,128.5,127.3,126.2,115.1,55.3,51.0,22.0ppm；HRMS(ESI) calculated[M+H]+for C17H21N2＝253.1699,found:253.1670.
实施例48
(S,E)-4-(4-cyclohexylbut-3-en-2-yl)morpholine:淡黄色油状液体，产率67％；ee
Figure BDA0002207447730000253
(m,1H),3.71(t,J＝4.7Hz,4H),2.81-2.74(m,1H),2.55-2.42(m,4H),1.97-1.89(m, 1H),1.74-1.67(m,4H),1.67-1.62(m,1H),1.32-1.16(m,3H),1.14(d,J＝6.5Hz, 3H),1.12-1.01(m,2H)ppm；13C NMR(100MHz,CDCl3)δ138.6,128.9,67.2,62.9, 50.5,40.4,33.1,33.0,26.2,26.0,18.0ppm；HRMS(ESI)calculated[M+H]+for C14H26NO＝224.2009,found:224.2011.
实施例49
(S,E)-1-(4-phenylbut-3-en-2-yl)piperidine-4-carboxamide:白色
Figure BDA0002207447730000261
3.05-3.00(m,1H),2.18-2.09(m,3H),1.94-1.87(m,2H),1.80-1.67(m,2H),1.25(d, J＝6.6Hz,3H)ppm；13C NMR(100MHz,CDCl3)δ177.7,137.0,132.2,130.7, 128.5,127.3,126.2,62.4,49.7,49.5,43.0,29.2,29.1,17.6ppm；HRMS(ESI) calculated[M+H]+for C16H23N2O＝218.1176,found:218.1177.
实施例50
(S,E)-8-chloro-11-(1-(4-phenylbut-3-en-2-yl)piperidin-4-ylidene)-6,11-dihydro-5
Figure BDA0002207447730000262
6.42(d,J＝15.9Hz,1H),6.25-6.19(m,1H),3.44-3.32(m,2H),3.20-3.11(m,1H), 2.93-2.74(m,4H),2.56-2.32(m,6H),1.26(d,J＝6.6Hz,3H)ppm；13C NMR(100 MHz,CDCl3)δ157.62,146.57,139.46,139.09,137.72,137.20,136.93,133.40, 132.56,132.38,132.08,130.90,130.82,128.93,128.51,127.34,126.24,125.94, 122.04,62.38,51.63,51.42,31.83,31.40,31.08,30.87,17.83ppm；3ay′:1H NMR (400MHz,CDCl3)δ8.40-8.38(m,1H),7.42(dd,J＝7.7,1.7Hz,1H),7.37-7.28(m, 4H),7.24-7.20(m,1H),7.14-7.11(m,3H),7.09-7.06(m,1H),6.42(d,J＝15.9Hz, 1H),6.25-6.19(m,1H),3.44-3.32(m,2H),3.20-3.11(m,1H),2.93-2.74(m,4H), 2.56-2.32(m,6H),1.26(d,J＝6.6Hz,3H)ppm；13CNMR(100MHz,CDCl3)δ 157.57,146.57,139.46,139.09,137.67,137.16,136.92,133.40,132.56,132.38, 131.97,130.87,130.77,128.90,128.51,127.34,126.22,125.94,122.04,62.35,51.63, 51.37,31.81,31.38,31.08,30.80,17.78ppm；HRMS(ESI)calculated[M+Na]+for C29H29ClN2Na＝463.1911,found:463.1907。

Claims (10)

1.一种高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于，包括以下步骤：在金属试剂Ni(COD)2、手性双膦配体和
Figure FDA0002207447720000012
酸添加剂作用下，将1,3-共轭二烯、胺溶于有机溶剂中并进行反应，经柱层析分离纯化得到手性烯丙基胺类化合物；所述方法合成路线如下：
Figure FDA0002207447720000011
2.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述1,3-共轭二烯为1-芳基或烷基取代的1,3-丁二烯。
3.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述1,3-共轭二烯取代基R包括：苯基、2-甲氧基苯基、4-甲氧基苯基、4-氟苯基、4-三氟甲基苯基、4-二甲氨基苯基、2-呋喃基、环己基。
4.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述胺包括：正丁胺、2-苯乙胺、环丙胺、环己胺、糠胺、2-(1-环己烯基)乙胺、烯丙基胺、(±)-四氢糠胺、N,N-二甲基乙二胺、苄胺、甘氨酸甲酯、(S)-1-苯乙胺、苯胺、4-甲基苯胺、4-溴-苯胺、乙醇胺、N-苄基乙二胺、2-羟基苄胺、4-氨基苯乙醇、色胺、4-氨基苄胺、吗啉、硫代吗啉、哌啶、四氢吡咯、吲哚啉、四氢异喹啉、1-(2-嘧啶基)哌嗪、N-甲基烯丙基胺、N-甲基苄胺、二苄胺、乙二胺、N-甲基苯胺。
5.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述的手性双膦配体为(S)-BIANP、(S)-SegPhos、(S)-SKP、(R)-SDP、(R)-DIOP、(S,S)-BDPP、(RC,SP)-DuanPhos、(S,S)-Me-DuPhos中的任一种，其具体结构如下所示：
Figure FDA0002207447720000021
6.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述的酸添加剂为苯甲酸、苯丙酸、苯基磷酸、邻苯二甲酸、对甲苯磺酸、对苯二甲酸、萘乙酸、邻羟基苯甲酸中的任一种，其具体结构如下所示：
Figure FDA0002207447720000022
7.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述的有机溶剂为甲醇、乙醇、异丙醇、三氟乙醇、六氟异丙醇、甲苯、三氟甲苯、二氯甲烷、1,2-二氯乙烷、氯仿、乙醚、1,4-二氧六环、四氢呋喃、甲基叔丁基醚、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、N-甲基吡咯烷酮、乙酸乙酯、乙腈、苄腈、乙二醇二甲醚、正己烷中的一种。
8.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：所述手性烯丙基胺类化合物的制备方法具体步骤如下：在惰性气体中，将金属试剂Ni(COD)2、手性双膦配体溶于干燥的有机溶剂中，然后加入1,3-共轭二烯、胺以及
Figure FDA0002207447720000024
酸添加剂，得到反应混合物，随后将上述反应混合物密封并从惰性气体中取出，反应完全后，减压浓缩除去有机溶剂，再经柱层析分离纯化得到目标产物手性烯丙基胺类化合物：
Figure FDA0002207447720000031
9.如权利要求1所述的高化学及立体选择性制备手性烯丙基胺类化合物的方法，其特征在于：金属试剂Ni(COD)2：手性双膦配体：
Figure FDA0002207447720000032
酸添加剂：1,3-共轭二烯：胺：有机溶剂的用量比为0.01mmol：0.01mmol：0.01mmol：0.2mmol：0.3mmol：1.0mL。
10.一种手性烯丙基胺类化合物，其特征在于，采用权利要求1～9任一项所述的方法制备得到。
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GAËL TRAN等: "Ni-Catalyzed Enantioselective Intermolecular Hydroamination of Branched 1,3-Dienes Using Primary Aliphatic Amines", 《J. AM. CHEM. SOC.》 *
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