重要三元杂环化合物开环反应机理及区域选择性的理论研究

The chemistry of three-membered heterocycles has important pratical applications in organic synthesis, and many useful synthetic methodologies based on the ring-opening of three-membered heterocylces have been developed. Further, three-membered heterocycles are key structure skeletons in natural products and pharmaceutical molecules. The ring-opening process of these heterocyles determines their biological activities in most cases. Therefore, investigations on the mechanism of the ring-opening process of three-membered heterocycles are significant for developing new synthetically useful reactions and understanding biological activities of relevant molecules. In this research project, we will study the mechanism, regioselectivity of the cleavage of C-C and C-X (X=O,N) bonds of a series of typical epoxides and aziridines catalyzed by transition-metal and Lewis acid catalysts. On the basis of density functional theory and other theoretical methods, we will clarify the relationships between catalysts and reactivity/regioselectivity (C-C vs. C-X (X=O,N)), investigate the cooperation effects, electronic and steric effects of different substituents on the reactivity and selectivity. This research project will establish the most favorable ring-opening mechanism of three-membered heterocyles and explore the origin of regioselective C-C and C-N cleavages. The result will provide useful clues for predicting the final products and for designing and synthesizing more effective transition-metal and Lewis acid catalysts for transformations of three-membered heterocyclic systems.

三元杂环在有机合成领域具有重要应用，而有关三元杂环开环反应的合成方法学也不断地被报道。同时，三元杂环也是天然产物和药物分子中的重要组成部分，而这些药物分子的生物活性往往由开环过程决定。因此，关于三元杂环开环反应机理的研究不仅能为发展新型的合成方法学提供理论支持，也对了解相关分子的生理活性具有重要意义。基于此，本项目拟对过渡金属以及路易斯酸催化条件下三元杂环C-C键和C-X（X=O,N）键断裂反应的机理及选择性展开研究。利用量子化学相关理论方法，深入研究体系反应活性中心，阐明催化剂自身性质与反应活性以及C-C键和C-X（X=O,N）键断裂选择性之间的关系，明确底物中取代基的导引协同，以及电子效应和位阻效应对反应的影响。本课题研究将建立有效的三元杂环反应机理和开环的选择性机理，为预测体系的最终产物和设计新型过渡金属催化和路易斯酸催化三元杂环C-C键和C-X（X=O,N）键断裂体系提供理论指导。

当前有机化学中选择性的、直接单步的过渡金属配合物和路易斯酸催化的方法不仅仅高效和经济，而且可以在化学选择性、区域选择性和立体选择性上表现出其卓著的优越性，因而受到了广泛的关注，是当前催化合成研究热点之一。本课题以理论与计算化学为基础，利用密度泛函理论对过渡金属催化和路易斯酸催化下各类反应的反应机理及区域选择性进行系统而深入的理论研究。从计算得到的分子轨道分布，NBO 电荷分布，静电势并结合扭曲能和相互作用能(Distortion/interaction)以及非共价相互作用(NCIs)分析对反应中所涉及到的活性中间体、反应路径、化学选择性和立体选择性等关键理论问题进行了详细的分析。并且通过计算确定了催化活性中心的结构特性、底物性质和反应机理，反应活性和反应选择性之间的规律。本课题研究为预测过渡金属催化和路易斯酸催化下各类反应体系的最终产物和设计新型过渡金属催化和路易斯酸催化体系提供了理论指导。