手性1-芳基四氢异喹啉类衍生物的合成新方法  

New Synthetic Method of Chiral 1-Aryltetrahydroisoquinoline Derivatives

作　　者：高豪泽 王佳欣 杨雪柔 刘瑞霞 聂慧芳[1] GAO Hao-ze;WANG Jia-xin;YANG Xue-rou;LIU Rui-xia;NIE Hui-fang(School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China;Department of Pharmacology, Xi'an Medical College, Xi'an 710021, China)

机构地区：[1]第四军医大学药学院,陕西西安710032 [2]西安医学院药学院,陕西西安710021

出　　处：《合成化学》2021年第8期679-685,共7页Chinese Journal of Synthetic Chemistry

基　　金：陕西省重点研发计划一般项目(2020SF-202)。

摘　　要：以1,2,3,4-四氢异喹啉为原料,先依次与二碳酸二叔丁酯、亚氯酸钠反应得到N-Boc-1,2,3,4-四氢-1-异喹啉酮,再和芳基格氏试剂反应得到分子内不对称还原胺化反应的底物,最后以ax-Josiphos为手性配体,[Ir(COD)Cl]_(2)为金属前体,在Ti(O^(i)Pr)_(4)和40%HBr溶液组成的催化体系中合成了8个手性1-芳基四氢异喹啉类化合物,其结构经^(1)H NMR和^(13)C NMR表征。该路线提供了一种以廉价1,2,3,4-四氢异喹啉为原料高效合成手性1-芳基四氢异喹啉类衍生物的新方法,为索利那新等药物的合成提供了新路径。N-Boc-1,2,3,4-tetrahydro-1-isoquinolinone was obtained by the reaction of 1,2,3,4-tetrahydroisoquinoline with di-tert-butyl dicarbonate and sodium chlorite,successively.Then Grignard reagent was added to synthesize the substrate for the intramolecular asymmetric reductive amination reaction.Finally,eight chiral 1-aryltetrahydroisoquinoline compounds were prepared by a highly efficient catalytic system composed of chiral ax-Josiphos ligand,[Ir(COD)Cl]_(2),Ti(O^(i)Pr)_(4) and 40%HBr aqueous solution,and the structures were characterized by ^(1)H NMR and ^(13)C NMR.This new synthetic route provides a new method for the efficient synthesis of chiral 1-aryltetrahydroisoquinoline derivatives using cheap 1,2,3,4-tetrahydroisoquinoline as a raw material,providing a new path for the synthesis of drugs,such as solifenacin,etc.

关 键 词：不对称还原胺化 手性四氢异喹啉 ax-Josiphos 铱催化 索利那新 合成 

分 类 号：O624.6[理学—有机化学]