基于异腈参与的[1+2+n]环化反应构建含氮杂环化合物研究

异腈化合物是一类重要的有机合成子，常被应用于很多含氮杂环化合物的合成中。在该研究领域中，由于异腈的亲核性较弱，其只能与亲电性较强的底物发生α-加成反应或者与具有强σ-电子受体金属作用发生金属插入反应。本项目通过亲核活化试剂增强异腈的亲核性，结合分子间开环反应以及分子内Friedel-Crafts/Mannich反应策略，分别研究异腈与D-A环丙烷、D-A吖啶以及D-A环丁烷的[1+2+n]环化反应，合成手性具有全碳季碳中心的螺吲哚啉化合物。该方法具有环境友好、原子经济的特性，体现了重要的基础研究价值。在此基础上，进一步建立大量制备手性螺环化合物的体系。同时，全合成具有重要生理活性的吲哚生物碱(–)-vincadifformine以及(–)-tabersonine，这一研究对于拓宽异腈[1+2+n]环化反应策略的应用范围具有重要指导意义。

Isocyanides are versatile building blocks for the synthesis of nitrogen-containing compounds. Because of the mild nucleophilicity of the carbon atom of the isocyanides group, it adds readily to reactive electrophile to perform α-addition reaction and coordinates transition metal which behaves as a good σ-electron acceptor to perform insertion reaction in this field. We wish to study formal [1+2+n] cyclization between isocyanides and Donor-Acceptor cyclopropanes、aziridines、cyclobutanes respectively in this project. This strategy combined an intermolecular Ring-Opening and an intramolecular Friedel-Crafts/Mannich reaction via the catalytic nucleophilic activation of isocyanides, which represents an environmentally benign, atom-economic way to construct highly functionalized nitrogen-spirocyclic indolines bearing all-carbon quaternary stereocenters. Furthermore, the catalytic system will be further optimized to realize practical synthesis of valuable nitrogen-heterocyclic compounds, and applied in the concise synthesis of bioactive indole alkaloids (–)-vincadifformine and (–)-tabersonine. This research will have important guiding significance for the further development of asymmetric formal [1+2+n] reactions of isocyanides.