亲核性亚胺衍生的1，n-偶极体环化反应研究

Nitrogen-containing heterocycles play an important role in the fields of drug discovery, material development, pesticide and small molecule probes. 1,n-Dipole-based (n>3 and conjugated 1,3-dipole) annulation has become a powerful tool for the synthesis of nitrogen-containing heterocycles, natural products and natural product-like molecules. Although much attention has been paid in the field of 1,n-dipole-based annulation and fruitful results have been achieved, there are drawbacks such as limited reaction pathways, narrow substrate scope and the use of expensive metal catalysts. This program aims to design novel 1,n-dipole-based annulations, such as 1,5-electrocyclization, 1,7-electrocyclization and 1,5-annulation 1,6-annulation, in order to develop new methods for the preparation of nitrogen-containing heterocycles. A range of annulations through the formation of nucleophilic imine-based 1,n-dipole intermediates is designed for the efficient construction of highly functionalized nitrogen-containing molecules, thus providing useful methods for the synthesis of important frameworks and natural products.

氮杂环化合物是药物研发、新材料研发、农药、小分子探针等研究领域的一类重要化合物。经由1，n-偶极体（n>3和共轭1，3-偶极体）途径的环化反应是合成氮杂环化合物和相关天然、类天然产物的重要工具。基于1，n-偶极体的分子内环化反应虽得以关注和发展，但是仍面临反应方式有限、底物范围窄和需要重金属参与等局限性。申请人拟设计基于亲核性亚胺的1，n-偶极体分子内环化反应，通过亲核性亚胺与受体试剂原位生成1，n-偶极体，从而实现1，5电环化、1，7电环化和1，5环化、1，6环化等环化反应，以期发展新颖的氮杂环合成方法学。本项目旨在设计和发展一系列基于亲核性亚胺的1，n-偶极体分子内环化反应，以便高效构建高度官能团化的氮杂环化合物，为重要氮杂环骨架化合物和类天然化合物的合成提供方法学基础。

本项目在基于亲核性亚胺衍生的1，n-偶极体环化领域进行探索和尝试，以1，n-偶极体环化反应作为关键反应步骤发展了多个铁催化、铜催化、无催化剂反应方法学，高效制备了高度官能团化的吡咯并异喹啉等重要类型的杂环化合物。不限于1，n-偶极体环化反应，其他可类比的环化反应也被设计发展、并应用于重要杂环化合物的合成。.本课题组在失败反应和意外结果的基础上进行发散和拓展。基于此，本研究组在吡咯并异喹啉和多取代吡咯等重要杂环化合物的修饰，尤其是基于二甲亚砜转化途径的杂环修饰领域积极开展了多项探索性工作和延伸拓展性研究、也取得了一定的研究结果并进行了报道。.