CN113024585B - 合成具有季碳手性中心的α-氨基酸酯类化合物的方法 - Google Patents
合成具有季碳手性中心的α-氨基酸酯类化合物的方法 Download PDFInfo
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Abstract
本发明涉及铜催化合成具有季碳手性中心的α‑氨基酸酯类化合物的反应。具体为,以酮亚氨基羧酸酯,联烯和联硼酸频那醇酯为原料,在铜卡宾催化的条件下,多组分反应合成具有季碳手性中心的α‑氨基酸酯类化合物。本发明有以下优点,廉价金属氯化亚铜和卡宾盐在碱条件下原位制备卡宾铜;室温下反应,条件温和;多组分反应;能够实现很好的非对映选择性和对映选择性调控,高达>20:1dr,96%ee。
Description
技术领域
本发明涉及一种铜催化合成具有季碳手性中心的α-氨基酸酯类化合物的方法。具体为,以酮亚氨基羧酸酯,联烯和联硼酸频那醇酯为原料,在铜卡宾催化的条件下,多组分反应合成具有季碳手性中心的α-氨基酸酯类化合物。本发明有以下优点,廉价金属氯化亚铜和卡宾盐在碱条件下原位制备卡宾铜;室温下反应,条件温和;多组分反应;能够实现很好的非对映选择性和对映选择性调控,高达>20:1dr,96%ee。
背景技术
具有季碳手性中心的α-氨基酸在具有特定生物活性的非天然肽和蛋白质的合成中起着关键作用,并且其在各种生物活性天然产物中都很普遍,例如sphingofungins E和F,altemicidin,和lactacystin。其中,氨基酸中的季碳中心具有阻碍外消旋作用并抑制构象灵活性的作用。
通过文献检索发现(式1),张万斌小组和王春江小组在2018年独立地报道了通过具有协同作用的Ir/Cu和Pd/Cu催化的醛亚胺酯的烯丙基化来获得具有连续立体中心(具有季碳手性中心)的手性氨基酯的方法(X.Huo,J.Zhang,J.Fu,R.He,W.Zhang,J.Am.Chem.Soc.2018,140,2080;L.Wei,Q.Zhu,S.-M.Xu,X.Chang,C.-J.Wang,J.Am.Chem.Soc.2018,140,1508.)。上述方法的成功取决于相邻的α-碳原子的亲核性,并且都是两组分的反应,相比之下,通过利用亚胺部分的亲电性,实现多组分的不对称合成同样十分重要。
发明内容
本发明目的在于以酮亚氨基羧酸酯,联烯和联硼酸频那醇酯为原料,在铜卡宾催化的条件下,多组分反应合成具有季碳手性中心的α-氨基酸酯类化合物,具有很好的非对映选择性和对映选择性。
本发明是通过以下技术方案实现的:
一种铜催化合成具有季碳手性中心的α-氨基酸酯类化合物的反应
酮亚氨基羧酸酯,联烯和联硼酸频那醇酯为原料,在铜卡宾催化的条件下,可以高非对映选择性和对映选择性生成具有连续手性中心的α-氨基酸酯类化合物。反应式如下所示:
具体操作步骤如下:
在氩气或氮气气氛下,于反应器中加入氯化亚铜,卡宾盐,叔丁醇钾,联硼酸频那醇酯和四氢呋喃溶剂,室温下搅拌反应1h,随后加入酮亚氨基羧酸酯与联烯,反应生成目标产物3。点板监测反应体系,反应结束后,旋干溶剂,柱层析流动相:石油醚/乙醚(体积比)
反应物酮亚氨基羧酸酯取代基R1可以是三氟甲基、苯基、4-甲基苯基、4-甲氧基苯基、4-三氟甲基苯基、4-甲硫基苯基、2-奈基、2-噻吩以及2-吡啶中的一种;反应物酮亚氨基羧酸酯取代基R2可以是甲基、乙基、正丙基、异丙基、叔丁基以及苄基中的一种;亚氨基酸酯取代基R3可以是4-甲氧基苯基、4-氟基苯基、4-溴苯基、4-氯苯基、4-吗啡啉苯基中的一种。
取代的联烯上的R4可以是环己基、苯基及取代的苯基、苄基及取代的苄基或萘基,取代的苯基中的取代基为-F、-Cl、-Br、-NO2,取代的苄基中的取代基为-F、-Cl、-Br、-NO2,以及苯氧基苄氧基中的一种、二种、三种或四种。
所用金属铜盐为下述中的一种或二种以上:氯化亚铜、溴化亚铜、碘化亚铜、氯化铜、溴化铜、碘化铜以及醋酸铜。其中,铜盐与酮亚氨基羧酸酯的摩尔比为0.001-1,优选范围为0.01-0.2。
所用卡宾盐试剂为下述中的一种或二种以上:L1、L2、L3、L4、L5、L6,(结构式如下式)卡宾盐试剂与与酮亚氨基羧酸酯的摩尔比为0.001-1,优选范围为0.01-0.2。
所用溶剂为,以甲醇、乙醇、异丙醇、叔丁醇、乙腈、甲苯、环己烷、四氢呋喃、2-甲基四氢呋喃、乙二醇二甲醚、甲基叔丁基醚、二氯甲烷、二氯乙烷、1,4-二氧六环、乙酸乙酯、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲亚砜中的一种或二种以上为溶剂,溶剂优选甲苯、四氢呋喃、1,4-二氧六环、二氯乙烷中的一种或两种,4-羟基香豆素于溶剂中优选浓度范围0.01-1.5mol/L。
联烯或取代的联烯用量是摩尔量的0.5-10倍之间,优选2-5倍之间;反应温度为室温条件;反应时间在0.5-36h之间,优选反应时间16-24h。
本发明具有如下优点:
本发明有以下优点,廉价金属氯化亚铜和卡宾盐在碱条件下原位制备卡宾铜;室温下反应,条件温和;多组分反应;能够实现很好的非对映选择性和对映选择性调控,高达>20:1dr,96%ee。因此,本专利在合成具有生物活性类分子方面有着潜在的应用前景。
附图说明
图1为化合物3aa的1H NMR和13C NMR图;
图2为化合物3ba的1H NMR,13C NMR和19F NMR图;
图3为化合物3ca的1H NMR和13C NMR图;
图4为化合物3da的1H NMR和13C NMR图;
图5为化合物3ea的1H NMR和13C NMR图;
图6为化合物3fa的1H NMR和13C NMR图;
图7为化合物3ga的1H NMR和13C NMR图;
图8为化合物3ha的1H NMR和13C NMR图;
图9为化合物3ia的1H NMR和13C NMR图;
图10为化合物3ja的1HNMR和13C NMR图;
图11为化合物3ka的1H NMR,13C NMR和19F NMR图;
图12为化合物4la的1H NMR和13C NMR图;
图13为化合物3aa的HPLC谱图;
图14为化合物3ba的HPLC谱图;
图15为化合物3ca的HPLC谱图;
图16为化合物3da的HPLC谱图;
图17为化合物3ea的HPLC谱图;
图18为化合物3fa的HPLC谱图;
图19为化合物3ga的HPLC谱图;
图20为化合物3ha的HPLC谱图;
图21为化合物3ia的HPLC谱图;
图22为化合物3ja的HPLC谱图;
图23为化合物3ka的HPLC谱图;
图24为化合物4la的HPLC谱图;
具体实施方式
下面将以具体的实施例来对本发明加以说明,但本发明的保护范围不局限于这些实例。
1.铜卡宾催化酮亚氨基羧酸酯,联烯和联硼酸频那醇酯的反应
在2.0mL封管中,依次加入氯化亚铜(5mol%,1.0mg),卡宾盐L(5mol%),叔丁醇钾(1.0equiv.,22.4mg),联硼酸频那醇酯(0.22mmol,55.9mg)和溶剂1mL,室温下搅拌反应1h,随后加入酮亚氨基羧酸酯(0.20mmol,56.6mg)与苯基联烯(0.30mmol,35.0mg),室温下反应16h,结束后加入均三甲氧基苯作为内标,1H NMR检测目标产物收率和非对映选择性,对映选择性通过手性HPLC测得。
表1.催化剂、溶剂对反应的影响
2.底物类型
在2.0mL封管中,依次加入氯化亚铜(5mol%,1.0mg),卡宾盐L6(5mol%),叔丁醇钾(1.0equiv.,22.4mg),联硼酸频那醇酯(0.22mmol,55.9mg)和溶剂1mL,室温下搅拌反应1h,随后加入酮亚氨基羧酸酯(0.20mmol,56.6mg)与苯基联烯(0.30mmol,35.0mg),室温下反应16h,点板监测反应体系,结束后旋干溶剂,柱层析分离,流动相为石油醚/乙酸乙酯(体积比50/1-5/1)可得到目标产物3。
(400MHz,CDCl3)δ7.71–7.62(m,2H),7.55–7.48(m,2H),7.28–7.16(m,6H),6.64–6.56(m,2H),6.36–6.25(m,2H),6.15(s,1H),5.70(d,J=3.0Hz,1H),5.17(d,J=3.0Hz,1H),4.31(s,1H),3.94(dq,J=10.7,7.1Hz,1H),3.80(dq,J=10.6,7.2Hz,1H),3.66(s,3H),1.21(s,6H),1.13(s,6H),0.80(t,J=7.1Hz,3H);13C NMR(100MHz,CDCl3)δ173.0,151.2,140.63,140.56,139.0,135.4,129.4,128.9,128.0,127.6,127.1,126.6,116.1,113.8,84.1,70.8,64.8,60.9,55.7,24.9,24.4,13.6;11B NMR(128MHz,CDCl3)δ31.0;HPLC:Chiracel AD-H column,254nm,30℃,n-hexane/i-propanol=95/5,flow=0.8mL/min,retention time 5.9min(maj)and 8.6min.
7.54–7.47(m,2H),7.28–7.20(m,5H),7.20–7.14(m,1H),6.73–6.67(m,2H),6.38(s,1H),6.31–6.24(m,2H),5.70(d,J=3.0Hz,1H),5.12(d,J=3.0Hz,1H),4.30(s,1H),3.95(dq,J=10.7,7.1Hz,1H),3.82(dq,J=10.8,7.1Hz,1H),1.22(s,6H),1.13(s,6H),0.82(t,J=7.1Hz,3H);13C NMR(100MHz,CDCl3)δ172.8,155.3(d,J=233.9Hz),142.8(d,J=1.9Hz),140.6,138.6,135.8,129.4,128.8,128.1,127.8,127.3,126.7,115.8(d,J=7.3Hz),114.5(d,J=22.2Hz).84.3,70.9,65.0,61.1,25.0,24.4,13.6;11B NMR(128MHz,CDCl3)δ30.2;19F NMR(376MHz,CDCl3)δ-129.56;HRMS calculated for C31H36NBO4F[M+H]+516.2716,found 516.2707;HPLC:Chiracel AD-Hcolumn,230nm,30℃,n-hexane/i-propanol=95/5,flow=1.0mL/min,retention time 4.2 min(maj)and 5.0min.
7.52–7.46(m,2H),7.27–7.14(m,7H),6.97–6.90(m,2H),6.59(s,1H),6.32–6.23(m,2H),5.69(d,J=3.0Hz,1H),5.07(d,J=3.0Hz,1H),4.29(s,1H),3.96(dq,J=10.7,7.1Hz,1H),3.85(dq,J=10.7,7.1Hz,1H),1.22(s,6H),1.12(s,6H),0.84(t,J=7.1Hz,3H);13C NMR(100 MHz,CDCl3)δ172.5,145.2,140.5,138.3,136.1,129.3,128.7,128.2,127.9,127.8,127.4,126.7,121.1,116.4,84.3,70.7,65.1,61.2,25.0,24.3,13.6;11B NMR(128MHz,CDCl3)δ31.7;HRMScalculated for C31H36NBO4Cl[M+H]+532.2420,found532.2420;HPLC:Chiracel IA column,254nm,30℃,n-hexane/i-propanol=95/5,flow=0.8mL/min,retention time 5.0min(maj)and 5.6min.
CDCl3)δ7.63–7.56(m,2H),7.50–7.48(m,2H),7.27–7.20(m,5H),7.21–7.12(m,1H),7.11–7.02(m,2H),6.62(s,1H),6.29–6.20(m,2H),5.69(d,J=3.0Hz,1H),5.06(d,J=3.0Hz,1H),4.29(s,1H),3.96(dq,J=10.7,7.1Hz,1H),3.85(dq,J=10.7,7.1Hz,1H),1.22(s,6H),1.12(s,6H),0.84(t,J=7.1Hz,3H);13C NMR(100MHz,CDCl3)δ172.4,145.6,140.4,138.2,136.1,130.8,129.2,128.6,128.2,127.9,127.4,126.7 116.9,108.3,84.3,70.7,65.1,61.3,25.0,24.3,13.6;11B NMR(128MHz,CDCl3)δ31.7;HRMS calculated forC31H36NBO4Br[M+H]+576.1915,found 576.1916;HPLC:Chiracel IA column,254nm,30℃,n-hexane/i-propanol=95/5,flow=0.8mL/min,retention time 5.1min(maj)and 5.7min.
7.68–7.61(m,2H),7.52–7.45(m,2H),7.27–7.08(m,6H),6.63–6.57(m,2H),6.32–6.23(m,2H),6.17(s,1H),5.71(d,J=3.0Hz,1H),5.18(d,J=3.0Hz,1H),4.31(s,1H),3.67(s,3H),3.39(s,3H),1.22(s,6H),1.14(s,6H);13C NMR(100MHz,CDCl3)δ173.8,151.3,140.6,140.4,138.8,135.7,129.4,129.0,128.1,127.7,127.2,126.7,116.0,114.0,84.2,71.0,65.0,55.8,51.9,25.0,24.5;11B NMR(128MHz,CDCl3)δ31.3;HRMS calculated forC31H37NBO5[M+H]+514.2759,found 514.2753;HPLC:Chiracel IA column,230nm,30℃,n-hexane/i-propanol=80/20,flow=0.8mL/min,retention time 5.2min(maj)and5.6min.
(400MHz,CDCl3)δ7.72–7.65(m,2H),7.56–7.51(m,2H),7.28–7.17(m,5H),7.18–7.13(m,1H),6.65–6.55(m,2H),6.36–6.28(m,2H),6.17(s,1H),5.67(d,J=3.1Hz,1H),5.11(d,J=3.1Hz,1H),4.85–4.72(m,1H),4.28(s,1H),3.67(s,3H),1.21(s,6H),1.11(s,6H),0.88(d,J=6.3Hz,3H),0.72(d,J=6.2Hz,3H);13C NMR(100MHz,CDCl3)δ172.3,151.2,140.8,139.3,135.3,129.6,128.9,128.0,127.6,127.1,126.5,116.2,113.8,84.1,70.7,68.9,64.9,55.8,25.0,24.4,21.4,20.9;11B NMR(128MHz,CDCl3)δ30.3;HRMS calculatedfor C33H41NBO5[M+H]+542.3072,found 542.3065;HPLC:Chiracel AD-H column,230nm,30℃,n-hexane/i-propanol=95/5,flow=0.8mL/min,retention time 5.9min(maj)and7.3min.
7.72–7.64(m,2H),7.51(dd,J=7.6,1.6Hz,2H),7.26–7.21(m,4H),7.21–7.14(m,2H),6.63–6.57(m,2H),6.32–6.27(m,2H),6.12(s,1H),5.69(d,J=3.1Hz,1H),5.17(d,J=3.0Hz,1H),4.31(s,1H),3.87–3.76(m,1H),3.67(s,3H),3.66–3.61(m,1H),1.28–1.25(m,2H),1.21(s,6H),1.13(s,6H),0.53(t,J=7.4Hz,3H);13C NMR(100MHz,CDCl3)δ173.3,151.3,140.71,140.74,139.1,135.5,129.4,129.0,128.1,127.7,127.2,126.6,116.1,113.9,84.2,71.0,66.8,65.0,55.9,25.0,24.5,21.5,10.4;11B NMR(128MHz,CDCl3)δ30.8;HRMS calculated for C33H41NBO5[M+H]+542.3072,found 542.3073;HPLC:Chiracel AD-Hcolumn,254nm,30℃,n-hexane/i-propanol=95/5,flow=1.0mL/min,retention time4.9min(maj)and 6.4min.
7.71–7.63(m,2H),7.51–7.46(m,2H),7.25–7.20(m,4H),7.22–7.15(m,3H),7.17–7.14(m,2H),6.85–6.78(m,2H),6.62–6.55(m,2H),6.33–6.26(m,2H),6.14(s,1H),5.70(d,J=3.1Hz,1H),5.15(d,J=3.0Hz,1H),4.94(d,J=12.4Hz,1H),4.68(d,J=12.4Hz,1H),4.32(s,1H),3.68(s,3H),1.21(s,6H),1.12(s,6H);13C NMR(100MHz,CDCl3)δ173.1,151.4,140.6,140.5,138.9,135.5,135.4,129.4,129.0,128.3,128.24,128.20,127.8,127.7,127.2,126.7,116.2,114.0,84.2,71.1,67.0,64.9,55.9,25.0,24.4;11B NMR(128MHz,CDCl3)δ30.3;HRMS calculated for C37H41NBO5[M+H]+590.3072,found 590.3074;HPLC:Chiracel IA column,230nm,30℃,n-hexane/i-propanol=80/20,flow=0.7mL/min,retention time 6.5min(maj)and 6.9min.
7.74–7.65(m,2H),7.58–7.52(m,2H),7.46–7.37(m,2H),7.26–7.22(m,2H),7.21–7.14(m,1H),6.60–6.54(m,2H),6.36–6.30(m,2H),6.19(s,1H),5.67(d,J=2.9Hz,1H),5.19(d,J=2.9Hz,1H),4.45(s,1H),3.97(dq,J=10.7,7.1Hz,1H),3.85(dq,J=10.9,7.2Hz,1H),3.64(s,3H),1.19(s,6H),1.10(s,6H),0.83(t,J=7.1Hz,3H);13C NMR(100MHz,CDCl3)δ173.1,151.4,140.7,137.0,135.7,133.2,132.6,129.5,128.8,128.1,127.9,127.5,127.4,126.8,126.7,126.0,125.6,116.2,113.9,84.1,71.0,64.7,61.1,55.8,24.9,24.5,13.7;11BNMR(128MHz,CDCl3)δ30.8;HRMS calculated for C36H41NBO5[M+H]+578.3072,found 578.3059;HPLC:Chiracel IA column,254nm,30℃,n-hexane/i-propanol=80/20,flow=0.8mL/min,retention time 5.4min(maj)and 8.6min.
(400MHz,CDCl3)δ7.61–7.53(m,2H),7.52–7.47(m,2H),7.38–7.34(m,2H),7.26–7.21(m,2H),7.21–7.15(m,1H),6.66–6.57(m,2H),6.32–6.22(m,2H),6.07(s,1H),5.74(d,J=2.9Hz,1H),5.25(d,J=3.0Hz,1H),4.24(s,1H),3.91(dq,J=10.7,7.1Hz,1H),3.76(dq,J=10.7,7.2Hz,1H),3.68(s,3H),1.21(s,6H),1.15(s,6H),0.77(t,J=7.1Hz,3H);13CNMR(100MHz,CDCl3)δ172.8,151.5,140.21,140.16,138.4,135.9,131.0,130.7,129.5,128.2,126.8,121.4,116.0,114.0,84.3,70.6,64.9,61.2,55.8,24.9,24.5,13.6;11B NMR(128MHz,CDCl3)δ29.4;HRMScalculated for C32H38NBO5Br[M+H]+606.2021,found606.2026;HPLC:Chiracel AD-H column,254nm,30℃,n-hexane/i-propanol=95/5,flow=1.0mL/min,retention time 5.0min(maj)and 12.0min.
Ethyl(2R,3S)-2-((4-methoxyphenyl)amino)-3-phenyl-4
2.0Hz,4H),7.31–7.22(m,2H),7.23–7.17(m,1H),6.64–6.59(m,2H),6.29–6.23(m,2H),6.13(s,1H),5.73(d,J=2.9Hz,1H),5.24(d,J=2.9Hz,1H),4.28(s,1H),3.92(dq,J=10.7,7.1Hz,1H),3.77(dq,J=10.7,7.1Hz,1H),3.68(s,3H),1.22(s,6H),1.15(s,6H),0.78(t,J=7.1Hz,3H);13C NMR(100MHz,CDCl3)δ172.7,151.6,143.4,140.1,140.0,135.9,129.5,129.2(q,J=32.8Hz),128.2,127.0,124.6(q,J=3.6Hz),124.4(q,J=272.4Hz),116.0,114.1,84.3,70.8,64.9,61.3,55.8,24.9,24.5,13.55;11B NMR(128MHz,CDCl3)δ31.2;19F NMR(376MHz,CDCl3)δ-62.4;HRMS calculated for C33H38NBO5F3[M+H]+596.2790,found 596.2792;HPLC:Chiracel AD-H column,254nm,30℃,n-hexane/i-propanol=95/5,flow=1.0mL/min,retention time 4.3min(maj)and 8.5min.
(400MHz,CDCl3)δ7.59–7.54(m,2H),7.53–7.48(m,2H),7.26–7.21(m,2H),7.19–7.14(m,1H),6.82–6.73(m,2H),6.64–6.58(m,2H),6.34–6.28(m,2H),6.08(s,1H),5.73(d,J=3.0Hz,1H),5.21(d,J=3.0Hz,1H),4.28(s,1H),3.93(dq,J=10.7,7.1Hz,1H),3.84–3.79(m,1H),3.78(s,3H),3.68(s,3H),1.22(s,6H),1.13(s,6H),0.81(t,J=7.1Hz,3H);13CNMR(100MHz,CDCl3)δ173.2,158.5,151.3,140.73,140.67,135.5,131.1,130.2,129.5,128.0,126.6,116.2,113.9,112.9,84.1,70.4,64.9,61.0,55.8,55.2,25.0,24.5,13.6;11BNMR(128MHz,CDCl3)δ31.4;HRMScalculated for C33H41NBO6[M+H]+558.3021,found.558.3020;HPLC:Chiracel IA column,254nm,30℃,n-hexane/i-propanol=80/20,flow=0.8mL/min,retention time 5.5min(maj)and 8.6min.
Claims (12)
1.合成具有季碳手性中心的α-氨基酸酯类化合物方法,其特征在于:
以酮亚氨基羧酸酯与联烯以及联硼酸频那醇酯在铜卡宾试剂的作用下,可以一次性合成具有两个相邻的手性中心,其中含有一个季碳手性中心的α-氨基酸酯类化合物;
所用卡宾盐试剂为下述中的L5、L6一种或二种:卡宾盐试剂与酮亚氨基羧酸酯的摩尔比为0.001-1;
反应物酮亚氨基羧酸酯取代基R1是三氟甲基、苯基、4-甲基苯基、4-甲氧基苯基、4-三氟甲基苯基、4-甲硫基苯基、2-萘基、2-噻吩基以及2-吡啶基中的一种;反应物酮亚氨基羧酸酯取代基R2是甲基、乙基、正丙基、异丙基、叔丁基以及苄基中的一种;酮亚氨基酸酯取代基R3是4-甲氧基苯基、4-氟基苯基、4-溴苯基、4-氯苯基、4-吗啡啉苯基中的一种;
取代的联烯上的R4是环己基、苯基及取代的苯基、苄基及取代的苄基或萘基,取代的苯基中的取代基为-F、-Cl、-Br、-NO2的一种或二种以上,取代的苄基中的取代基为-F、-Cl、-Br、-NO2、以及苯氧基、苄氧基中的一种或二种以上。
2.根据权利要求1所述的方法,其特征在于:具体操作步骤如下:
在氩气或氮气气氛下,于反应器中加入铜盐,卡宾盐,叔丁醇钾,联硼酸频那醇酯和四氢呋喃溶剂,室温下搅拌反应1h,随后加入酮亚氨基羧酸酯与联烯和/或取代的联烯,反应生成目标产物3。
3.根据权利要求2所述的方法,其特征在于:
点板监测反应体系,反应结束后,旋干溶剂,柱层析流动相:石油醚/乙醚。
4.根据权利要求1-3任一所述的方法,其特征在于:
所用金属铜盐为下述中的一种或二种以上:氯化亚铜、溴化亚铜、碘化亚铜、氯化铜、溴化铜、碘化铜以及醋酸铜;其中,铜盐与酮亚氨基羧酸酯的摩尔比为0.001-1。
5.根据权利要求4所述的方法,其特征在于:
铜盐与酮亚氨基羧酸酯的摩尔比为0.01-0.2。
6.根据权利要求1-3任一所述的方法,其特征在于:
所用溶剂为甲醇、乙醇、异丙醇、叔丁醇、甲苯、环己烷、四氢呋喃、2-甲基四氢呋喃、乙二醇二甲醚、甲基叔丁基醚、二氯甲烷、二氯乙烷、1,4-二氧六环、乙酸乙酯、N,N-二甲基甲酰胺、N-甲基吡咯烷酮、二甲亚砜中的一种或二种以上,酮亚氨基羧酸酯于溶剂中浓度范围0.01-1.5 mol/L。
7.根据权利要求6所述的方法,其特征在于:
所用溶剂为甲苯、四氢呋喃、1,4-二氧六环、二氯乙烷中的一种或两种以上。
8.根据权利要求1-3任一所述的方法,其特征在于:
联烯和/或取代的联烯用量是酮亚氨基羧酸酯摩尔量的0.5-10倍之间;
反应温度为室温条件;反应时间在0.5-36 h之间。
9.根据权利要求8所述的方法,其特征在于:
联烯和/或取代的联烯用量是酮亚氨基羧酸酯摩尔量的2-5倍之间;
反应温度为室温条件;反应时间16-24h。
10.根据权利要求1-3任一所述的方法,其特征在于:
联硼酸频那醇酯用量是酮亚氨基羧酸酯摩尔量的1.0-10倍之间;
叔丁醇钾用量是酮亚氨基羧酸酯摩尔量的0.1-5.0倍之间。
11.根据权利要求1-3任一所述的方法,其特征在于:
联硼酸频那醇酯用量是酮亚氨基羧酸酯摩尔量的1.2-5.0倍之间;
叔丁醇钾用量是酮亚氨基羧酸酯摩尔量的0.5-2.0倍之间。
12.根据权利要求1所述的方法,其特征在于:卡宾盐试剂与酮亚氨基羧酸酯的摩尔比为0.01-0.2。
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