Key Laboratory of Drug-Targeting and Drug Delivery System of the Ministry of Education and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
College of Pharmacy, Third Military Medical University, Chongqing, 400038, China.
Angew Chem Int Ed Engl. 2020 Apr 27;59(18):7083-7088. doi: 10.1002/anie.202000044. Epub 2020 Mar 9.
The catalytic diastereodivergent construction of stereoisomers having two or more stereogenic centers has been extensively studied. In contrast, the switchable introduction of another stereogenic element, that is, Z/E configuration involving a polysubstituted alkene group, into the optically active stereoisomers, has not been recognized yet. Disclosed here is the pseudo-stereodivergent synthesis of highly enantioenriched tetrasubstituted alkene architectures from isatin-based Morita-Baylis-Hillman carbonates and allylic derivatives, under the cooperative catalysis of a tertiary amine and a chiral iridium complex. The success of the switchable construction of the tetrasubstituted alkene motif relies on the diastereodivergent 1,3-oxo-allylation reaction between N-allylic ylides and chiral π-allyliridium complex intermediates by ligand and substrate control, followed by the stereoselective concerted 3,3-Cope rearrangement process.
具有两个或更多手性中心的立体异构体的催化非对映选择性构建已经得到了广泛的研究。相比之下，将另一个手性元素（即涉及多取代烯烃基团的 Z/E 构型）可切换地引入到光学活性的立体异构体中尚未被认识到。本文公开了一种从基于色胺的 Morita-Baylis-Hillman 碳酸酯和烯丙基衍生物在叔胺和手性铱配合物的协同催化下，通过假对映选择性合成高对映过量的四取代烯烃结构的方法。四取代烯烃结构的可切换构建的成功依赖于 N-烯丙基叶立德与手性π-烯丙基铱配合物中间体之间的通过配体和底物控制的非对映选择性 1,3-氧代-烯丙基化反应，然后是立体选择性协同的 3,3-Cope 重排过程。
