手性吡咯烷、哌啶和氮杂䓬环等含氮杂环以及相应的稠环或桥环是天然生物碱的核心结构和药物分子的优势骨架，因此已经成为有机合成和创新药物研究中最重要的研究热点之一。亚甲胺叶立德作为一种非常重要的1,3-偶极子，不仅在不对称合成领域得到广泛的应用，同时在创新药物研究中取得了突破性成果。本项目希望在前期开展的亚甲胺叶立德参与的催化不对称[3+2]环加成反应研究的基础上，结合新型“三中心和四中心亲1,3-偶极子”的设计理念，发展一系列新型的基于亚甲胺叶立德参与的催化不对称1,3-偶极[3+3]/[4+3]环加成反应，合成一系列具有结构多样性和潜在生理活性的手性哌啶和氮杂䓬等含氮杂环及其相应的稠环衍生物，并形成相应的化合物库用于活性测试。本项目研究不仅将丰富催化不对称环加成反应的化学内涵，同时也为发展高效、高立体选择性的催化不对称1,3-偶极环加成反应提供新的策略，以及为创新药物研究提供新颖的先导结构。

Chiral nitrogen-containing heterocycles, such as pyrrolidine、pyperidine and azepine, as well as their corresponding fused and bridged skeletons, are core structures existing in natural alkaloids, and privileged scaffolds for drug molecules, consequently has been emerging as an important and hot research topic in the field of organic synthesis and drug discovery. Azomethine ylide as an important 1,3-dipole has not only been widely applied for the asymmetric synthesis, but also made a breakthrough in the drug discovery. Recently, we have developed a series of highly effective and stereoselective 1,3-dipolar cycloaddition of azomethine ylides with a variety of electron-deficient alkenes. On the basis of our recently developed azomethine chemistry, combined with new concept and design of “three-centre and four-centre 1,3-dipolarphiles”, we are dedicated to develop a series of highly efficient and stereo selective 1,3-dipolar [3+3]/[4+3]cycloaddition of azomethine ylides for the synthesis of a variety of diversity-oriented and biologically active chiral nitrogen-containing heterocycle derivatives, including chiral six-membered pyperidine and seven-membered azepine, as well as their corresponding fused and bridged skeleton, which will be used for biological test. In conclusion, this project could greatly enrich the chemistry of catalytic asymmetric 1,3-dipolar cycloaddition of azomethine ylides, and provide a new way and strategy for developing highly efficient and stereoselective 1,3-dipolar cycloaddition, and dilivery structurally novel lead compounds for drug discovery.