原位生成烯丙基亚胺离子分子内环化反应研究

In situ formed iminium ion initiated intramolecular cyclization reaction provides a powerful synthetic tool for construction of C-C, C-N bonds and cyclic compounds, which has been widely utilized in the synthesis of many natural products and drugs. There are two modes of cyclization being involved in this reaction, namely endo-mode and exo-mode. Up to now, only a rather limited number of examples of exo-mode cyclizations have been reported for the synthesis of all-carbon ring skeletons and heterocycles, in contrast, the endo-mode cyclizations are widely used to formation of nitrogen-containing heterocycles, such as Pictet-Spengler reaction. In this project, we planned to develop a new synthetic protocol for efficient assembly of carbocyclic and nitrogen-containing heterocyclic ring skeletons, via an in situ formed allylic iminium ion initiated intramolecular exo-mode cyclization. Additionally, the mechanism and asymmetric version of this reaction will also be investigated. This study will not only enrich the chemistry of iminium ion cyclization, but also lay a foundation for complicated molecules synthesis.

原位生成的亚胺离子引发的分子内环化反应是构建碳碳键、碳氮键和环状化合物的重要方法，被广泛应用于天然产物和药物分子的合成。这一反应具有内型和外型两种关环模式，目前报道的方法主要采用内型关环模式，比如Pictet-Spengler反应，用来构建含氮杂环化合物，应用外型关环模式来构建全碳环和杂环的研究报道很少。本申请项目将对取代烯丙醛原位生成的亚胺离子引发的外型关环反应开展研究，发展高效构建全碳环或氮杂环的反应方法和策略，并对该反应的机理和不对称催化开展研究。本项目的研究内容，可以丰富亚胺离子环化反应的类型，并为复杂分子的骨架构建提供研究基础。

本课题以烯丙基亚胺离子串联环化反应为关键策略，通过外型关环模式，发展了几种高效构建全碳环、氮杂环和多芳烃体系的反应方法和催化体系。这些方法具有很高的合成效率和原子经济性，同时催化剂和原料便宜易得、环境友好，因而具有良好的应用前景。本课题的研究成果可以丰富亚胺离子加成反应在有机合成中的应用，并为复杂分子的骨架构建提供研究基础。