由环丙基酮生成铵叶立德并进行[2,3] - 迁移重排以合成具有桥头季碳立体中心的手性吲哚里西啶

Generation and [2,3]-Sigmatropic Rearrangement of Ammonium Ylides from Cyclopropyl Ketones for Chiral Indolizidines with Bridgehead Quaternary Stereocenters.

作者信息

Xi Song, Jiang Yan, Yang Jiaojiao, Yang Jiao, Miao Dingyin, Chen Baoyi, Huang Wanqiu, He Ling, Qiu Hanyue, Zhang Min

机构信息

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.

Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou 341000, China.

出版信息

Org Lett. 2022 Sep 30;24(38):6957-6961. doi: 10.1021/acs.orglett.2c02759. Epub 2022 Sep 16.

DOI:10.1021/acs.orglett.2c02759

PMID:36112353

Abstract

A sequence of nucleophilic ring opening of cyclopropyl ketones, -quaternization, deprotonation, and [2,3]-sigmatropic rearrangement of ammonium ylides has been developed. This method enables efficient synthesis of bicyclic indolizidines bearing bridgehead aza-quaternary stereocenters from easily available chiral cyclopropyl ketones. The reactions proceeded with an excellent level of chirality transfer and tolerated various functional groups, providing a diverse array of allenyl- or allyl-substituted indolizidines with high enantiomeric purities (up to >99% ee).

摘要

已开发出一种环丙基酮的亲核开环、α-季铵化、去质子化以及铵叶立德的[2,3]-σ迁移重排序列。该方法能够从易于获得的手性环丙基酮高效合成带有桥头氮杂季碳立体中心的双环吲哚里西啶。反应具有出色的手性转移水平，并且能耐受各种官能团，可提供多种具有高对映体纯度（高达>99% ee）的烯丙基或烯丙基取代的吲哚里西啶。