不对称Prins/氮杂-Prins环化反应研究

Prins/氮杂-Prins环化反应作为有机合成重要的构筑碳-碳键的方法之一，可高效的合成四氢吡喃、哌啶等广泛存在于天然产物和药物分子中的化合物。通过底物控制的不对称Prins环化反应构筑吡喃环已被作为关键步骤应用于复杂天然产物的合成中。然而更具应用前景的催化不对称Prins环化反应至今尚未被突破。本项目经过分析不对称Prins环化反应的关键因素，结合有机小分子催化前沿，采用两种策略探索催化不对称Prins/氮杂-Prins环化反应：一种是采用手性硫脲控制布朗斯特酸阴离子来控制反应中的活泼中间体氧鎓离子/亚胺离子；另一种是直接使用手性酸控制活泼中间体。项目的实施，将揭示催化不对称Prins/氮杂-Prins环化反应的一些基本规律，建立不对称催化体系，为高效合成手性四氢吡喃、哌啶等化合物提供一条可行方法。

The Prins/aza-Prins cyclization is one of the fundamental synthetic method for C-C bond formation, and an efficient method for the preparation of tatrahydropyran and piperidine compounds which are common structural feature of numerous natural products and pharmaceutical molecules. The substrate-controlled strategy of asymmetric Prins cyclization has been used for the construction of tetrahydropyran in the synthesis of complex natural products as key step. However, the catalytic asymmetric Prins cyclization, a more powerful method, has not yet been achieved. After analysis of the key factor of asymmetryic Prins cyclization, and combination of the frontier of organocatalysis, this project will explore the catalytic asymmetric Prins/aza-Prins cyclization by two strategies: one is controlling oxonium ion or iminium ion of the reaction intermediate by chiral thiourea and achiral Bronsted acid; the other is controlling the acitive intermediate by chiral Bronsted acid directly. This project will also explore some rules of the Prins/aza-Prins cyclization, and the catalytic asymmetric system would be developed, which will offer an efficent method for the convenient synthesis of chiral tetrahydropyran and piperidine compoounds.