Yu Zhang-Long, Cheng Yong-Feng, Jiang Na-Chuan, Wang Jian, Fan Li-Wen, Yuan Yue, Li Zhong-Liang, Gu Qiang-Shuai, Liu Xin-Yuan
Shenzhen Grubbs Institute, Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology Shenzhen 518055 China
Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology Shenzhen 518055 China
Chem Sci. 2020 May 20;11(23):5987-5993. doi: 10.1039/d0sc00001a.
Although great success has been achieved in catalytic asymmetric hydroamination of unactivated alkenes using transition metal catalysis and organocatalysis, the development of catalytic desymmetrising hydroamination of such alkenes remains a tough challenge in terms of attaining a high level of stereocontrol over both remote sites and reaction centers at the same time. To address this problem, here we report a highly efficient and practical desymmetrising hydroamination of unactivated alkenes catalysed by chiral Brønsted acids with both high diastereoselectivity and enantioselectivity. This method features a remarkably broad alkene scope, ranging from mono-substituted and -/1,2-disubstituted to the challenging tri- and tetra-substituted alkenes, to provide access to a variety of diversely functionalized chiral pyrrolidines bearing two congested tertiary or quaternary stereocenters with excellent efficiency under mild and user-friendly synthetic conditions. The key to success is indirect activation of unactivated alkenes by chiral Brønsted acids a concerted hydroamination mechanism.
尽管在使用过渡金属催化和有机催化实现未活化烯烃的催化不对称氢胺化方面已经取得了巨大成功，但就同时在远程位点和反应中心实现高水平的立体控制而言，开发此类烯烃的催化去对称化氢胺化仍然是一项艰巨的挑战。为了解决这个问题，我们在此报告了一种由手性布朗斯特酸催化的高效且实用的未活化烯烃去对称化氢胺化反应，该反应具有高非对映选择性和对映选择性。此方法的特点是烯烃范围非常广泛，从单取代、1,2 - 二取代到具有挑战性的三取代和四取代烯烃，能够在温和且用户友好的合成条件下高效地获得各种带有两个拥挤叔碳或季碳立体中心的功能多样的手性吡咯烷。成功的关键是手性布朗斯特酸对未活化烯烃的间接活化——一种协同氢胺化机制。
