Wieland-Miescher（W-M）酮类化合物在药物和天然产物合成等方面具有重要的科学意义和经济价值，而有机小分子不对称催化的分子内aldol反应是合成该类化合物的重要方法。针对目前该类反应普遍存在底物适用范围较窄、产率和立体选择性不高等问题，本项目申请人拟采用密度泛函理论对最近出现的新型有机小分子催化剂催化此类反应的反应机理进行系统的研究，找出最佳反应通道，重点分析催化剂的结构与反应活性、立体选择性及反应速率之间的关系，探索催化剂、底物、环境等因素对相关反应机理的调控规律，进而为无溶剂条件下构建更有活性的催化剂以及提高反应的空间选择性和反应速率提供理论指导，为进一步的实验优化和新型高效有机小分子催化剂的设计提供重要的理论参考数据。

Wieland-Miescher (W-M) ketone compounds possess important scientific significance and economic value in drug and natural product synthesis. Organocatalytic intramolecular aldol reaction is an important synthetic method for these compounds. At present, there are many problems in this kind of reaction, such as limitation of substrate application, low yield and poor stereoselectivity. In this project, density functional theory (DFT) will be applied to study the reaction mechanism of this reaction catalyzed by newly developed organocatalysis, aiming to find the optimum reaction channel, to analyze the relationship between the catalyst structure and the reaction activity, stereoselectivity and reaction rate, and also to explore the regulation principles of catalyst, substrate and environment on the reaction mechanism. The investigations will provide the theoretical guidance for the development of more active catalysts under solvent-free conditions and improvement on the stereoselectivity and reaction rate. The obtained theoretical data will be notably valuable for further experimental optimization and the design of higher efficient organocatalysts.