路易斯酸促进的SN2'反应合成胺及含氮杂环化合物

胺类化合物广泛存在于自然界，具有重要的生物和生理活性。目前市场上在售的大多数药物也是胺或胺的衍生物。发展胺的新合成方法是研究含氮生物活性分子的基础，也是更好地维护人类健康的重要基点之一。该项目从方便、易得，且具有高反应活性的N-氧代烯胺出发，（1）在路易斯酸存在下，与分子间和分子内的亲核位点以SN2'方式作用，生成取代的亚胺中间产物；（2）通过在N-氧代烯胺中引入具有离去能力的三甲基硅基，设计生成N-烯基亚胺中间体，并与烯烃或炔烃发生[4+2]环加成反应，生成多取代的氢化吡啶中间产物；（3）在过渡金属和手性配体的催化下，亲核试剂以SN2'方式与N-氧代烯胺反应，生成α取代的手性亚胺中间产物，这些中间产物经过原位还原，即可得到β取代的胺衍生物和氮杂环化合物。该类方法可以在胺的β碳原子上构建新的碳-碳、碳-杂原子键，实现通过C-N键偶联难以进行的转化，为复杂含氮化合物的合成提供新的策略和途径。

Amines are ubiquitous in molecules of importance to biology and medicine. Most of clinical drugs in use are amines or their derivatives. Development of new synthetic route to amines is fundamental to the research of amino bioactive molecules, and of importance to safeguarding human health. This project starts from readily available, highly active N-vinylalkoxylamine derivatives, (1) in the presence of Lewis acid, couple with either inter- or intra- molecular nucleophile in the form of SN2’, thus provide substituted imine intermediate; (2) by introducing a movable TMS group in the starting N-vinylalkoxylamine, strategically generate N-vinylimine active intermediates, which react with either alkene or alkyne, delivering hydro pyridine product; (3) catalyzed by transition metal and chiral ligand, N-vinylalkoxylamine is deracemizatively coupled with nucleophile, providing α-substituted imine product, these imine products undergo hydrogenation in situ afterwards, furnishing β-substituted amines and N-heterocycles. These methodologies allow the construction of new C-C and C-X bond at the β carbon of amine, which will be an interesting and useful complement to the classical C-N coupling reactions in the synthesis of amines.