Xu Chao, Muir Calum W, Leach Andrew G, Kennedy Alan R, Watson Allan J B
EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, UK.
Angew Chem Int Ed Engl. 2018 Aug 27;57(35):11374-11377. doi: 10.1002/anie.201806956. Epub 2018 Aug 1.
The direct enantioselective synthesis of chiral azaheteroaryl ethylamines from vinyl-substituted N-heterocycles and anilines is reported. A chiral phosphoric acid (CPA) catalyst promotes dearomatizing aza-Michael addition to give a prochiral exocyclic aryl enamine, which undergoes asymmetric protonation upon rearomatization. The reaction accommodates a broad range of N-heterocycles, nucleophiles, and substituents on the prochiral centre, generating the products in high enantioselectivity. DFT studies support a facile nucleophilic addition based on catalyst-induced LUMO lowering, with site-selective, rate-limiting, intramolecular asymmetric proton transfer from the ion-paired prochiral intermediate.
报道了从乙烯基取代的氮杂环和苯胺直接对映选择性合成手性氮杂芳基乙胺。手性磷酸（CPA）催化剂促进去芳构化氮杂迈克尔加成反应，生成前手性环外芳基烯胺，该烯胺在重新芳构化时发生不对称质子化。该反应适用于多种氮杂环、亲核试剂以及前手性中心上的取代基，能以高对映选择性生成产物。密度泛函理论（DFT）研究表明，基于催化剂诱导的最低未占分子轨道（LUMO）降低，亲核加成反应较为容易，且存在位点选择性、速率限制的分子内不对称质子从离子对前手性中间体转移的过程。
