CN116283459A - 一种合成亚甲基酰胺取代环己烷的方法 - Google Patents
一种合成亚甲基酰胺取代环己烷的方法 Download PDFInfo
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Abstract
本发明公开了一种合成亚甲基酰胺取代环己烷的方法,所述方法包括:在有机溶剂中和惰性气体氛围下,将式2所示的环外烯烃和式3所示的酰胺化试剂在金属镍类催化剂NiA、配体L、氢源、离子添加剂和质子添加剂的作用下进行反应,反应结束后经后处理,得到式1所示的亚甲基酰胺取代环己烷,反应式如下:其中,R1为未取代或取代的烷基、芳基、酯基、氨基、取代胺基、酰胺基、磺酰基、烷氧基、硅醚、硫醚、炔基、卤素中的一种或多种;所述R2为未取代或取代的烷基、芳基、烷氧基、硅醚、硫醚、炔基中的一种或多种。
Description
技术领域
本发明涉及有机合成技术领域,特别涉及一种合成亚甲基酰胺取代环己烷的方法。
背景技术
有机胺类化合物在制药、材料和有机合成领域有着广泛的应用。C-N键形成反应是药物化学中最广泛使用的一些反应。其中,烯烃的分子间氢化反应是将含氮基团引入可广泛获得的原料化学品的重要方法。但是现有技术中而成亚甲基酰胺取代环己烷的方法存在底物实用性不强、操作繁琐等缺点。
因此,一种更为可行的思路是研究寻找一种合成热力学不稳定的亚甲基酰胺取代环己烷类化合物的高效方法。
发明内容
本发明目的是提供一种合成亚甲基酰胺取代环己烷的方法,该方法操作简便,原料便宜易得,底物官能团兼容性好,具有良好的区域选择性及立体选择性。
为了实现上述目的,本发明采用如下技术方案:
本发明提供了一种合成亚甲基酰胺取代环己烷的方法,所述方法包括:
在有机溶剂中和惰性气体氛围下,将式2所示的环外烯烃和式3所示的酰胺化试剂在金属镍类催化剂NiA、配体L、氢源、离子添加剂和质子添加剂的作用下进行反应,反应结束后经后处理,得到式1所示的亚甲基酰胺取代环己烷,反应式如下:
其中,R1为未取代或取代的烷基、芳基、酯基、氨基、取代胺基、酰胺基、磺酰基、烷氧基、硅醚、硫醚、炔基、卤素中的一种或多种;所述R2为未取代或取代的烷基、芳基、烷氧基、硅醚、硫醚、炔基中的一种或多种;
所述的配体L选自如下的一种:
进一步地,所述的离子添加剂,其阳离子为Li+、Na+、K+、Mg2+、Zn2+、Cs+中的任一种,阴离子为F–、Cl–、Br–、I–、[CH3COO]–、[CF3COO]–中的任一种。
进一步地,所述的氢源为聚甲基氢硅氧烷、三甲氧基氢硅烷、三乙氧基氢硅烷、二乙氧基甲基氢硅烷、三乙基氢硅烷、二苯基氢硅烷、二甲氧基甲基氢硅烷、三苯基氢硅烷、硼烷及其复合物、频哪醇硼烷中的任一种。
进一步地,所述的质子添加剂为水、甲醇、异丙醇、叔丁醇中的一种或几种。
进一步地,所述的有机溶剂为甲醇、乙醇、异丙醇、四氢呋喃、2-甲基四氢呋喃、1,4-二氧六环、乙醚、甲基叔丁基醚、乙二醇二甲醚、乙二醇二乙醚、N-甲基吡咯烷酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、苯、甲苯、二甲苯、三甲苯、氯苯、1,2-二氯苯、乙酸乙酯、丙酮、乙腈、苯乙腈、C3-C12的饱和烷基腈中的一种或几种。
进一步地,所述的金属镍类催化剂NiA中,A为Cl–、Br–、I–、[CH3COO]–、[CF3COO]–、[acac]–、Br–带1个乙二醇二甲醚、[NO3]–带4个结晶水中的任一种。
进一步地,所述的配体L为如下的任一种:
进一步地,所述金属镍类催化剂NiA:配体:氢源:离子添加剂:质子添加剂:环外烯烃:酰胺化试剂:有机溶剂的用量比为摩尔:摩尔:摩尔:摩尔:摩尔:摩尔:体积mL=0.05:0.05:5:5:1:1.5:0.75。
进一步地,所述反应温度为-20~40℃。
进一步地,所述式1所示的亚甲基酰胺取代环己烷包括:
进一步地,所述后处理包括减压浓缩除去有机溶剂,再经柱层析分离纯化。
本发明实施例中的一个或多个技术方案,至少具有如下技术效果或优点:
本发明提供一种合成1,3-二取代环类化合物的方法,通过特定配体的使用,使环外烯烃,氢源和酰胺化试剂,在金属镍催化剂作用下,一锅法反应制备酰胺类的有机化合物,该反应方法不但可以高效地合成目标化合物,而且底物适用性强,具有优秀的区域选择性(rr>99:1)和立体选择性(dr>99:1),此方法所使用的原料廉价易得,操作简便,底物官能团兼容性好,可以高效地合成酰胺类化合物。
具体实施方式
下面将结合实施例对本发明的方案进行解释。本领域技术人员将会理解,下面的实施例仅用于说明本发明,而不应视为限定本发明的范围。实施例中未注明具体技术或条件的,按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。使用的方法如无特别说明,均为本领域公知的常规方法,使用的耗材和试剂如无特别说明,均为市场购得。除非另有说明,本文中所用的专业与科学术语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法或材料也可应用于本发明中。
下述实施例中,NiBr2·DME是指溴化镍(II)乙二醇二甲醚,(MeO)3SiH是指三甲氧基氢硅烷,1,4-dioxane是指1,4-二氧六环。THF是指四氢呋喃。
下面将结合实施例、对比例及实验数据对本申请的一种合成亚甲基酰胺取代环己烷的方法进行详细说明。
实施例1
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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87%)。1H NMR(600MHz,Chloroform-d)δ7.84–7.69(m,2H),7.54–7.46(m,1H),7.46–7.37(m,2H),6.17(s,1H),3.49(dd,J=7.8,5.8Hz,2H),1.95(ddh,J=7.5,5.1,2.4Hz,1H),1.77–1.73(m,2H),1.60–1.55(m,2H),1.51(tt,J=13.6,4.5Hz,2H),1.19(qd,J=13.1,3.4Hz,2H),1.00(tt,J=12.1,3.2Hz,1H),0.85(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ167.6,134.9,131.3,128.6,126.9,48.5,41.2,33.0,32.6,28.6,27.5,21.9ppm;HRMS(ESI)calculated[M+H]+for C18H28NO+=274.2165,found:274.2159.
实施例2
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1b(88.2mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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%)。1H NMR(600MHz,Chloroform-d)δ7.82–7.70(m,2H),7.53–7.45(m,1H),7.42(dd,J=8.3,6.9Hz,2H),6.20(s,1H),3.42(dd,J=7.6,5.9Hz,2H),1.86–1.79(m,1H),1.79–1.72(m,4H),1.55–1.40(m,8H),1.30(q,J=7.4Hz,2H),1.19–1.09(m,5H),0.93–0.79(m,7H)ppm;13C NMR(151MHz,Chloroform-d)δ167.6,135.0,131.3,128.6,126.9,43.1,41.7,40.3,39.8,37.5,35.3,33.5,30.4,27.4,25.6,20.1,14.5ppm;HRMS(ESI)calculated[M+H]+forC23H36NO+=342.2791,found:342.2785.
实施例3
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1c(99.4mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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%)。1H NMR(600MHz,Chloroform-d)δ7.81–7.71(m,2H),7.53–7.46(m,1H),7.45–7.38(m,2H),6.19(s,1H),3.40(dd,J=7.4,5.9Hz,2H),1.75(dt,J=11.0,3.6Hz,1H),1.73–1.70(m,4H),1.51(dddd,J=21.1,12.2,7.8,3.9Hz,4H),1.45–1.33(m,5H),1.33–1.24(m,4H),1.18–1.06(m,6H),0.90–0.81(m,7H)ppm;13C NMR(151MHz,Chloroform-d)δ167.6,135,131.3,128.6,126.9,43.8,39.9,38.2,37.6,36.0,35.5,35.2,33.5,33.4,31.4,28.7,26.7,20.1,14.5ppm;HRMS(ESI)calculated[M+H]+for C25H40NO+=370.3104,found:370.3108.
实施例4
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1d(94.5mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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88%)。1H NMR(600MHz,Chloroform-d)δ7.76(d,J=7.6Hz,2H),7.48(t,J=7.4Hz,1H),7.42(t,J=7.5Hz,2H),6.27(s,1H),3.93(d,J=3.0Hz,4H),3.42(t,J=6.7Hz,2H),1.85–1.80(m,1H),1.76(d,J=11.0Hz,4H),1.54–1.41(m,10H),1.23(d,J=9.1Hz,4H)ppm;13CNMR(151MHz,Chloroform-d)δ167.6,134.9,131.3,128.5,126.9,109.1,64.2,64.2,43.0,40.7,38.9,35.2,34.7,27.5,27.3,25.7ppm;HRMS(ESI)calculated[M+H]+for C22H32NO3 +=358.2377,found:358.2374.
实施例5
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1f(116.2mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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%)。1H NMR(400MHz,Chloroform-d)δ7.79–7.74(m,2H),7.51–7.45(m,1H),7.45–7.38(m,2H),7.08–7.01(m,1H),6.98(ddd,J=11.9,7.8,2.1Hz,1H),6.88(ddt,J=8.1,3.8,1.7Hz,1H),6.20(t,J=5.8Hz,1H),3.43(dd,J=7.6,6.0Hz,2H),2.39(tt,J=12.3,3.2Hz,1H),1.95–1.80(m,5H),1.56–1.43(m,8H),1.36(td,J=13.2,12.5,3.6Hz,2H),1.26–1.15(m,2H),1.10–0.98(m,2H)ppm;13C NMR(101MHz,Chloroform-d)δ167.7,144.9,135.0,131.4,128.7,126.9,122.7,122.6,122.6,116.9,116.8,115.6,115.4,43.8,43.0,41.6,39.8,35.3,34.5,30.6,27.4,25.6ppm;19F NMR(376MHz,Chloroform-d)δ-138.6,-142.4.
实施例6
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1g(96.5mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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78%)。1H NMR(600MHz,Chloroform-d)δ7.88–7.74(m,4H),7.74–7.64(m,2H),7.54–7.46(m,1H),7.43(td,J=7.7,7.3,1.8Hz,2H),6.37(s,1H),4.15(tt,J=12.6,4.4Hz,1H),3.66(dd,J=7.9,6.0Hz,2H),2.44(qd,J=13.1,3.7Hz,2H),2.13(ddt,J=7.6,5.0,2.8Hz,1H),1.90–1.85(m,2H),1.66(tt,J=13.9,4.4Hz,2H),1.63–1.53(m,2H)ppm;13CNMR(151MHz,Chloroform-d)δ168.4,167.6,134.8,133.9,132.0,131.4,128.6,126.9,123.1,50.4,41.0,31.8,27.3,24.4ppm;HRMS(ESI)calculated[M+H]+for C22H23N2O3 +=363.1703,found:363.1699.
实施例7
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1h(68.9mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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78%)。1H NMR(600MHz,Chloroform-d)δ7.82–7.73(m,2H),7.53–7.47(m,1H),7.43(dd,J=8.3,6.9Hz,2H),7.30(t,J=7.6Hz,2H),7.25(s,2H),7.21–7.16(m,1H),6.19(t,J=6.1Hz,1H),3.57(dd,J=7.7,5.9Hz,2H),2.61(tt,J=10.3,3.8Hz,1H),2.02(dp,J=7.9,4.9,3.9Hz,1H),1.73(qdd,J=15.4,10.7,8.7Hz,8H)ppm;13C NMR(151MHz,Chloroform-d)δ167.7,146.9,134.9,131.4,128.6,128.3,127.0,126.9,125.9,43.3,41.9,33.6,28.9,28.0ppm;HRMS(ESI)calculated[M+H]+for C20H24NO+=294.1852,found:294.1854.
实施例8
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1i(68.9mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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78%)。1H NMR(600MHz,Chloroform-d)δ7.82–7.73(m,2H),7.53–7.47(m,1H),7.43(dd,J=8.3,6.9Hz,2H),7.30(t,J=7.6Hz,2H),7.25(s,2H),7.21–7.16(m,1H),6.19(t,J=6.1Hz,1H),3.57(dd,J=7.7,5.9Hz,2H),2.61(tt,J=10.3,3.8Hz,1H),2.02(dp,J=7.9,4.9,3.9Hz,1H),1.73(qdd,J=15.4,10.7,8.7Hz,8H)ppm;13C NMR(151MHz,Chloroform-d)δ167.7,146.9,134.9,131.4,128.6,128.3,127.0,126.9,125.9,43.3,41.9,33.6,28.9,28.0ppm;HRMS(ESI)calculated[M+H]+for C20H24NO+=294.1852,found:294.1854.
实施例9
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1j(90.5mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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(浅黄色油,产率55%)。1H NMR(600MHz,Chloroform-d)δ7.85–7.78(m,2H),7.51–7.46(m,1H),7.42(ddt,J=8.2,6.6,1.2Hz,2H),6.44(t,J=6.2Hz,1H),3.73(s,3H),3.67(s,3H),3.57(dt,J=13.5,6.8Hz,1H),3.39(d,J=10.3Hz,1H),3.30(ddd,J=13.8,8.5,5.5Hz,1H),2.45(dtd,J=13.8,7.9,3.6Hz,1H),2.04–1.98(m,1H),1.65–1.50(m,5H),1.44–1.35(m,2H),1.30(dtd,J=14.8,10.7,9.5,4.8Hz,1H)ppm;13C NMR(151MHz,Chloroform-d)δ169.3,169.1,167.4,134.7,131.3,128.5,126.9,55.6,52.4,52.4,42.9,33.0,32.8,32.6,29.6,28.7,20.7ppm;HRMS(ESI)calculated[M+H]+for C19H26NO5 +=348.1805,found:348.1808.
实施例10
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1k(60.9mg,0.4mmol)和2a(97.8mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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48%)。1H NMR(600MHz,Chloroform-d)δ7.80–7.74(m,2H),7.52–7.46(m,1H),7.46–7.39(m,2H),6.11(s,1H),3.47(dd,J=8.9,6.0Hz,2H),2.16(ddq,J=10.4,7.1,3.5Hz,1H),1.83–1.69(m,4H),1.64(tdq,J=12.3,6.5,3.2Hz,1H),1.49(dp,J=9.6,6.5Hz,1H),1.15–1.08(m,1H),1.09–1.01(m,1H),0.99(d,J=6.7Hz,3H),0.92(d,J=6.5Hz,3H),0.92–0.86(m,1H),0.85(d,J=6.4Hz,3H)ppm;13C NMR(151MHz,Chloroform-d)δ167.7,135.0,131.3,128.6,126.8,47.2,37.4,37.2,35.6,35.5,29.5,26.2,25.4,22.8,21.8,20.8ppm;HRMS(ESI)calculated[M+H]+for C18H28NO+=274.2165,found:274.2162.
实施例11
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2b(115.9mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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%)。1H NMR(600MHz,Chloroform-d)δ7.74(d,J=8.9Hz,2H),6.96–6.86(m,2H),6.18(s,1H),3.83(s,3H),3.46(dd,J=7.8,5.8Hz,2H),1.94(ddq,J=7.8,5.0,2.6Hz,1H),1.77–1.71(m,2H),1.58–1.53(m,2H),1.49(tt,J=13.6,4.5Hz,2H),1.18(qd,J=13.0,3.4Hz,2H),1.00(dt,J=12.2,3.2Hz,1H),0.84(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ167.1,162.0,128.6,127.2,113.7,55.4,48.4,41.1,33.0,32.6,28.6,27.5,21.9ppm;HRMS(ESI)calculated[M+H]+for C19H30NO2 +=304.2271,found:304.2269.
实施例12
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2c(118.5mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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%)。1H NMR(600MHz,Chloroform-d)δ7.75–7.67(m,2H),7.44–7.35(m,2H),6.13(d,J=6.0Hz,1H),3.48(dd,J=7.8,5.8Hz,2H),1.94(ttt,J=7.2,4.5,2.2Hz,1H),1.76–1.71(m,2H),1.59–1.55(m,2H),1.51(tt,J=13.7,4.5Hz,2H),1.18(qd,J=13.0,3.4Hz,2H),1.00(tt,J=12.2,3.2Hz,1H),0.85(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ166.5,137.5,133.3,128.8,128.3,48.4,41.3,33.0,32.6,28.6,27.5,21.9ppm;HRMS(ESI)calculated[M+H]+for C18H27ClNO+=308.1775,found:308.1774.
实施例13
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2d(101.5mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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63%)。1H NMR(600MHz,Chloroform-d)δ7.51(dt,J=3.7,1.3Hz,1H),7.45(dd,J=5.0,1.1Hz,1H),7.06(ddd,J=4.8,3.7,0.9Hz,1H),6.11(s,1H),3.46(dd,J=7.8,5.9Hz,2H),1.93(dqd,J=7.6,5.0,2.4Hz,1H),1.76–1.71(m,2H),1.56(dd,J=13.2,3.5Hz,2H),1.49(tt,J=13.6,4.5Hz,2H),1.17(qd,J=13.0,3.4Hz,2H),0.99(tt,J=12.0,3.1Hz,1H),0.84(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ161.9,139.2,129.6,127.8,127.6,48.4,41.2,33.1,32.6,28.6,27.5,21.9ppm;HRMS(ESI)calculated[M+H]+for C16H26NOS+=280.1729,found:280.1724.
实施例14
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2e(198.2mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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%)。1H NMR(600MHz,Chloroform-d)δ7.84(dd,J=5.4,3.0Hz,2H),7.73(dd,J=5.4,3.0Hz,2H),6.21(t,J=5.7Hz,1H),3.70(dd,J=13.9,4.3Hz,1H),3.63(dd,J=13.9,8.3Hz,1H),3.23(ddd,J=13.5,7.8,5.7Hz,1H),3.16(ddd,J=13.4,7.7,5.7Hz,1H),2.48–2.38(m,1H),2.16(qd,J=14.3,6.4Hz,2H),1.80(dt,J=13.3,6.6Hz,2H),1.67(ddt,J=16.4,13.7,2.9Hz,2H),1.51(td,J=9.4,8.2,4.0Hz,2H),1.44(tq,J=13.1,4.1Hz,2H),1.22(t,J=7.1Hz,2H),1.14–1.04(m,2H),0.97(t,J=3.2Hz,1H),0.95(d,J=6.6Hz,3H),0.91(d,J=6.6Hz,3H),0.82(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ171.4,169.0,134.0,131.9,123.3,48.4,41.9,41.5,40.7,39.9,33.5,32.8,32.5,28.6,27.5,25.2,22.7,22.6,21.8,21.8ppm;HRMS(ESI)calculated[M+H]+for C27H41N2O3 +=441.3111,found:441.3118.
实施例15
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2f(207.1mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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73%)。1H NMR(600MHz,Chloroform-d)δ7.08–7.04(m,2H),6.63–6.60(m,2H),5.42(d,J=6.1Hz,1H),3.70(t,J=6.8Hz,4H),3.62(t,J=7.1Hz,4H),3.28(dd,J=7.8,5.8Hz,2H),2.56(t,J=7.5Hz,2H),2.17(t,J=7.5Hz,2H),1.92(p,J=7.5Hz,2H),1.79(ddt,J=8.0,5.7,2.5Hz,1H),1.66(dq,J=13.7,2.1Hz,2H),1.53(dd,J=13.1,3.2Hz,2H),1.45(tt,J=13.6,4.4Hz,2H),1.12(qd,J=13.2,3.5Hz,2H),0.97(tt,J=12.1,3.2Hz,1H),0.83(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ172.8,144.3,130.8,129.7,112.2,53.6,48.4,40.6,40.6,36.1,34.1,33.0,32.6,28.6,27.5,21.8ppm;HRMS(ESI)calculated[M+H]+forC25H41Cl2N2O+=455.2590,found:455.2579.
实施例16
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1a(60.9mg,0.4mmol)和2g(200.6mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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60%)。1H NMR(600MHz,Chloroform-d)δ7.63–7.59(m,2H),7.57–7.54(m,2H),7.37–7.30(m,6H),6.20(t,J=5.9Hz,1H),3.28(dd,J=7.9,5.8Hz,2H),3.20(t,J=7.1Hz,2H),2.76(t,J=7.1Hz,2H),1.78(dqd,J=7.6,5.1,2.4Hz,1H),1.65–1.60(m,2H),1.48–1.43(m,2H),1.38(tt,J=13.5,4.4Hz,2H),1.07(qd,J=13.4,3.4Hz,2H),0.95–0.91(m,1H),0.80(s,9H)ppm;13C NMR(151MHz,Chloroform-d)δ171.3,162.5,145.5,134.9,132.4,128.9,128.7,128.6,128.5,128.1,127.9,126.5,48.4,40.8,33.2,32.8,32.5,28.5,27.5,24.2,21.8ppm;HRMS(ESI)calculated[M+H]+for C29H37N2O2 +=445.2849,found:445.2837.
实施例17
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1h(68.9mg,0.4mmol)和2h(111.1mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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68%)。1H NMR(600MHz,Chloroform-d)δ7.28(t,J=7.6Hz,2H),7.25–7.20(m,2H),7.17(td,J=7.2,1.4Hz,1H),5.68(t,J=5.8Hz,1H),3.35(dd,J=7.7,5.9Hz,2H),2.58(tt,J=9.9,4.4Hz,1H),2.17(t,J=7.6Hz,2H),1.87(tt,J=7.9,3.9Hz,1H),1.76–1.59(m,10H),1.34–1.22(m,8H),0.87(t,J=6.9Hz,3H)ppm;13C NMR(151MHz,Chloroform-d)δ173.3,147.0,128.3,126.9,125.9,43.3,41.3,36.9,33.5,31.7,29.3,29.1,28.8,27.9,25.9,22.6,14.1ppm.
实施例18
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1h(68.9mg,0.4mmol)和2i(101.5mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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84%)。1H NMR(600MHz,Chloroform-d)δ7.28(t,J=7.6Hz,2H),7.25–7.21(m,2H),7.20–7.14(m,1H),5.47(s,1H),3.35(dd,J=7.7,5.9Hz,2H),2.58(tt,J=9.8,4.3Hz,1H),2.08(tt,J=11.8,3.5Hz,1H),1.90–1.83(m,3H),1.79(dt,J=12.2,3.2Hz,2H),1.75–1.62(m,9H),1.44(qd,J=12.2,3.4Hz,2H),1.31–1.18(m,3H)ppm;13C NMR(151MHz,Chloroform-d)δ176.2,146.9,128.3,127.0,125.8,45.7,43.3,41.0,33.6,29.9,28.8,27.9,25.8,25.8ppm;HRMS(ESI)calculated[M+H]+for C20H30NO+=300.2321,found:300.2313.
实施例19
在充满氩气的手套箱中,将溴化镍(II)乙二醇二甲醚(6.2mg,0.02mmol)、配体L1(5.0mg,0.02mmol)、碘化钠(18.0mg,0.12mmol)、(MeO)3SiH(254μL,2mmol)溶于1.2mL干燥的1,4-二氧六环和0.3mL干燥的四氢呋喃的混合溶剂中,然后加入烯烃1h(68.9mg,0.4mmol)和2j(162.6mg,0.6mmol),将反应管密封并从手套箱中取出,在20℃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(橘黄色固体,产率45%)。1H NMR(600MHz,Chloroform-d)δ7.33–7.27(m,2H),7.27–7.24(m,2H),7.18(ddt,J=7.5,6.7,1.5Hz,1H),5.76(t,J=6.1Hz,1H),4.67(t,J=1.9Hz,2H),4.36–4.31(m,2H),4.19(s,5H),3.50(dd,J=7.7,6.1Hz,2H),2.66–2.57(m,1H),1.98(dt,J=7.8,3.9Hz,1H),1.82–1.67(m,8H)ppm;13C NMR(151MHz,Chloroform-d)δ170.2,147.0,128.3,127.0,125.9,76.5,70.3,69.7,69.7,68.1,43.4,41.3,33.8,28.9,28.0ppm;HRMS(ESI)calculated[M+H]+for C24H28FeNO+=402.1514,found:402.1505.
最后,还需要说明的是,术语“包括”、“包含”或者其任何其他变体意在涵盖非排他性的包含,从而使得包括一系列要素的过程、方法、物品或者设备不仅包括那些要素,而且还包括没有明确列出的其他要素,或者是还包括为这种过程、方法、物品或者设备所固有的要素。
尽管已描述了本发明的优选实施例,但本领域内的技术人员一旦得知了基本创造性概念,则可对这些实施例作出另外的变更和修改。所以,所附权利要求意欲解释为包括优选实施例以及落入本发明范围的所有变更和修改。
显然,本领域的技术人员可以对本发明进行各种改动和变型而不脱离本发明的精神和范围。这样,倘若本发明的这些修改和变型属于本发明权利要求及其等同技术的范围之内,则本发明也意图包含这些改动和变型在内。
Claims (10)
2.根据权利要求1所述的方法,其特征在于,所述的离子添加剂,其阳离子为Li+、Na+、K+、Mg2+、Zn2+、Cs+中的任一种,阴离子为F–、Cl–、Br–、I–、[CH3COO]–、[CF3COO]–中的任一种。
3.根据权利要求1所述的方法,其特征在于,所述的氢源为聚甲基氢硅氧烷、三甲氧基氢硅烷、三乙氧基氢硅烷、二乙氧基甲基氢硅烷、三乙基氢硅烷、二苯基氢硅烷、二甲氧基甲基氢硅烷、三苯基氢硅烷、硼烷及其复合物、频哪醇硼烷中的任一种。
4.根据权利要求1所述的方法,其特征在于,所述的质子添加剂为水、甲醇、异丙醇、叔丁醇中的一种或几种。
5.根据权利要求1所述的方法,其特征在于,所述的有机溶剂为甲醇、乙醇、异丙醇、四氢呋喃、2-甲基四氢呋喃、1,4-二氧六环、乙醚、甲基叔丁基醚、乙二醇二甲醚、乙二醇二乙醚、N-甲基吡咯烷酮、N,N-二甲基甲酰胺、N,N-二甲基乙酰胺、二甲基亚砜、二氯甲烷、1,2-二氯乙烷、氯仿、四氯化碳、苯、甲苯、二甲苯、三甲苯、氯苯、1,2-二氯苯、乙酸乙酯、丙酮、乙腈、苯乙腈、C3-C12的饱和烷基腈中的一种或几种。
6.根据权利要求1所述的方法,其特征在于,所述的金属镍类催化剂NiA中,A为Cl–、Br–、I–、[CH3COO]–、[CF3COO]–、[acac]–、Br–带1个乙二醇二甲醚、[NO3]–带4个结晶水中的任一种。
7.根据权利要求1所述的方法,其特征在于,所述金属镍类催化剂NiA:配体:氢源:离子添加剂:质子添加剂:环外烯烃:酰胺化试剂:有机溶剂的用量比为摩尔:摩尔:摩尔:摩尔:摩尔:摩尔:体积mL=0.05:0.05:5:5:1:1.5:0.75。
8.根据权利要求1所述的方法,其特征在于,所述惰性气体选自氩气或氮气。
9.根据权利要求1所述的方法,其特征在于,所述反应温度为-20~40℃。
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