苯甲酸催化的三组分[3+2]环加成反应合成六氢吡咯并[2,1-a]异喹啉化合物  

Benzoic Acid Catalyzed Three-component[3+2]Cycloaddition for the Synthesis of Hexahydroyrrolo[2,1-a]isoquinoline Compounds

作　　者：蒋少栋 江多镀 马晓明[1] 刘建武[1] 严生虎[1] 张跃[1] JIANG Shao-dong;JIANG Duo-du;MA Xiao-ming;LIU Jian-wu;YAN Sheng-hu;ZHANG Yue(School of Pharmacy,Changzhou University,Changzhou 213164,China)

机构地区：[1]常州大学药学院,江苏常州213164

出　　处：《化学试剂》2022年第5期777-785,共9页Chemical Reagents

基　　金：江苏省研究生科研创新计划项目(KYCX21_2864)。

摘　　要：发展了一种合成六氢吡咯并[2,1-a]异喹啉化合物的新方案,以苯甲酸为催化剂,4?分子筛为添加剂,催化芳香醛、1,2,3,4-四氢异喹啉和N-取代马来酰亚胺经串联的醛胺缩合和[3+2]环加成反应,合成了一系列六氢吡咯并[2,1-a]异喹啉化合物。主要考察了催化剂、溶剂、反应时间及反应温度对产物产率的影响,最终确定在60℃下,以10 mL超干甲苯为溶剂,20 mol%苯甲酸为催化剂,加入250 mg分子筛,以n(芳香醛)∶n(1,2,3,4-四氢异喹啉)∶n(N-取代马来酰亚胺)=1∶1.3∶1.2反应2 h。产物结构经;HNMR、;CNMR和HRMS等手段表征,产物(8R,8aR,11aS,11bR)-8-(2-氯苯基)-10-甲基-5,6,8,8a,11a,11b-六氢-9H-吡咯并[3′,4′∶3,4]吡咯并[2,1-a]异喹啉-9,11(10H)-二酮空间立体结构由单晶X射线衍射确定。A novel protocol for the synthesis of hexahydroyrrolo[2,1-a]isoquinoline compounds was developed,using benzoic acid as catalyst via three-component reaction with aromatic aldehydes,1,2,3,4-tetrahydroisoquinoline and N-substituted maleimides through sequential condensation and[3+2]cycloaddition with 4?molecular sieves as additives.The effects of catalyst,solvent,reaction time and reaction temperature on the yields of the products were investigated.The optimized conditions for the one-pot synthesis were found to conduct the reaction with aromatic aldehydes,1,2,3,4-tetrahydroisoquinoline and N-substituted maleimides(mass ratio of substances 1∶1.3∶1.2)using benzoic acid(20 mol%)as catalyst,in the presence of 250 mg 4?molecular sieves in 10 mL ultra-dry toluene at 60℃for 2 h.The products were confirmed by;HNMR,;CNMR,HRMS,the stereochemistry of product(8R,8aR,11aS,11bR)-8-(2-chlorophenyl)-10-methyl-5,6,8,8a,11a,11b-hexahydro-9H-pyrrolo[3′,4′∶3,4]pyrrolo[2,1-a]isoquinoline-9,11(10H)-dione was confirmed by single crystal X-ray diffraction.

关 键 词：苯甲酸 1 2 3 4-四氢异喹啉 [3+2]环加成反应 六氢吡咯并[2 1-a]异喹啉 

分 类 号：TQ20[化学工程—有机化工]