动力学控制的钼催化烯烃复分解反应机理的理论研究

Olefin metathesis reaction is one of the key transformations to build natural products and complex drug molecules in synthetic chemistry. This reaction transforms olefin to olefin, and the similarity between the reactants and products makes the highly efficient catalysts achieving the thermodynamic equilibrium of the catalytic process. Such thermodynamically controlled reactions cannot selectively control the Z,E-stereoselectivity of the olefin product, which limits the synthetic application of olefin metathesis reaction. Focusing on this issue,the proposed studies aim to study the mechanism and selectivities of kinetically controlled Mo-catalyzed olefin metathesis reactions, from the perspective of physical organic chemistry and using density functional theory calculations.This proposal will reveal the controlling fators of thermodynamic and kinetic controls, establish the transition state model of the kinetically controlled stereoselectivity, and explain the origins of the substrate- and ligand-based stereoselectivity. Based on the explanations of the existing experimental results, we will try to develop the design principle to modify and improve the kinetically controlled molybdenum catalysts, and to expand the substrate scope of related olefin metathesis reactions. The findings will facilitate the synthetic chemists to design more efficient and selective olefin metathesis reactions, improving the synthetic applications of olefin metathesis reactions.

烯烃复分解反应是合成化学中构建天然产物和药物分子的重要转化。由于此类反应由烯烃制烯烃，反应物和产物的类似性使得高效的催化剂往往会实现催化过程的热力学平衡。这种热力学控制的过程导致产物烯烃的顺反立体构型难以专一的调控，限制了烯烃复分解反应在合成中的应用。针对这一问题，本项目从物理有机化学的角度出发，采用密度泛函计算的方法，进行动力学控制的钼催化烯烃复分解反应的机理研究，阐明区分热力学控制和动力学控制的决定因素，建立动力学控制立体选择性的过渡态模型，从而揭示配体和底物控制立体选择性的机制。在验证和解释现有实验结果的基础上，尝试提出改良动力学控制的钼催化剂的基本原则和拓展相关烯烃复分解反应底物的核心策略，辅助合成化学家设计更高效和选择性的烯烃复分解反应，使烯烃复分解反应在合成化学中发挥更加重要的作用。

烯烃复分解反应是构建复杂天然产物、药物分子和聚合物材料的一类重要方法，在合成化学及高分子材料化学等领域具有重要意义。该类反应自上世纪50年代中期发现以来，设计与合成高效催化剂一直是该领域的研究核心。本项目通过计算化学的方法，对包含膦配体、氮双芳基卡宾配体、氮双烷基卡宾配体以及氮双芳基不对称卡宾配体的催化烯烃关环复分解反应和烯烃交叉复分解反应进行了系统研究，阐明了相关转化的微观机制，发现了烯烃复分解反应中的线性自由能关系，并基于线性自由能关系构建了烯烃复分解反应的热力学火山图，从而在分子层面明确了影响催化活性的控制因素，为实验科学家理性设计烯烃复分解催化剂提供了理论模型。