银(Ⅰ)/手性磷酸协同催化不对称合成吲哚N-C芳基轴手性化合物

吲哚N-C芳基轴手性化合物是一类具有重要药用性和合成应用性的轴手性化合物，它们广泛存在于天然化合物、药物及手性配体中。关于这类轴手性化合物的不对称催化合成，主要局限于一键合成策略；而串联式合成策略，目前只有一例报道。就催化体系而言，目前也局限于单一的催化体系。金属-有机小分子的协同不对称催化体系在吲哚轴手性化合物的合成中，目前尚待研究。利用金属-有机小分子的协同不对称催化体系，发展高效的新串联合成策略以合成吲哚N-C芳基轴手性化合物就尤为值得期待。基于此，本项目以发展“吲哚N-C芳基轴手性化合物的不对称合成新策略”为目标，结合“C-炔基-N,O-缩醛”的特色化学，利用银盐-手性磷酸的协同不对称催化体系，发展炔基亚胺的协同催化不对称[3+2]环加成反应。同时，拓展炔基亚胺的催化不对称新反应；发展萘胺化合物的不对称催化F-C反应。更为重要的是，该项目将探索协同催化不对称体系中手性起源的多向性。

Axially chiral N-arylindoles are one class of biologically and synthetic important atropisomeric compounds and are widely prevalence in natural products, drugs and chiral ligands for asymmetric catalysis. Currently, the asymmetric synthetic strategies for the axially chiral N-arylindoles manily suffered from the limitation of one-bond formation. And only one reported was involved the cascaded synthetic strategy. Moreover, of these strategies are only catalyzed by the single catalysis. To employ Metal-Organic Dual Catalysis (MODC) for the synthesis of axial indoles remained elusive. Hence, it is highly desirable to develop a new cascaded synthetic strategy to enable access to axially chiral N-arylindoles, especially by the Metal-Organic Dual Catalysis. Based on the chemistry of C-alkynyl-N,O-acetals, this project herein designed to develop the cooperative silver(І)/chiral phosphoric acid catalyzed asymmetric [3+2]-annulation of alkynyl imines, which could provide a new and facile synthetic methodology for the synthesis of axially chiral N-arylindoles. Meanwhile, this project would explore the new asymmetric reaction of alkynyl imines, and demonstrated the catalytic asymmetric F-C reaction of naphthylamines. Of these, the most important is to explore the versatility of chiral origin in the cooperative dual catalysis.