经由[3+3]环加成/[3,3]重排构建十元氮杂环化合物

中环骨架化合物的合成一直是有机合成中的难点和富有挑战性的课题之一。通过分子内反应构建十元氮杂环化合物目前已经取得了重要进展，但是经由分子间反应构建十元氮杂环化合物，特别是其对映选择性和非对映选择性控制，目前还鲜有报道。本项目计划发展N-烯基硝酮与ɑ-卤代试剂瞬时生成的1,3-偶极子发生[3+3]环加成/[3,3]-重排串联反应快速构建含两个或多个手性中心的十元氮杂环化合物的新方法，通过电子效应和空间位阻效应调控反应选择性；同时实现含两个或多个手性中心的十元氮杂环化合物的对映选择性合成。在此基础上，将所发展的方法应用到若干吲哚内过氧生物碱的构建和修饰中。本项目的研究为快速合成含两个或多个手性中心的十元氮杂环化合物提供一条有效的途径，为中环骨架化合物的构建提供新的思路。目前，初步的研究结果证明了该项目的可行性。

The synthesis of medium-sized ring compounds has always been one of the most difficult and challenging topics in organic synthesis. Up to now, the preparation of ten-membered aza-heterocycles has been made great advance through intramolecular reaction. However, the construction of ten-membered aza-heterocycles by intermolecular reaction, especially for its enantioselectivity and diastereoselectivity control, was rarely reported. In this project, we developed a new cascade strategy for the rapid construction of ten-membered aza-heterocycles containing two or multiple stereocenters by using [3+3] cycloaddition /[3,3]-rearrangement of N-vinyl nitrones and the 1,3-dipoles in situ generated from ɑ-halogenated reagents. We would also study the reaction selectivity control by electronic effect and steric hindrance effect. At the same time, the enantioselective synthesis of ten-membered aza-heterocycles containing two or multiple stereocenters was realized. Based on these results, the developed methods were applied in the synthesis or modifications of some indole endoperoxide alkaloids. This project will not only provide an effective pathway to the rapid construction of ten-membered aza-heterocycles containing two or multiple stereocenters, but also provide a new idea for the synthesis of medium-sized ring compounds. At present, the preliminary research results have proved the feasibility of this project.