有机膦催化的环加成反应是构建重要杂环骨架的高效方法, 从文献报道中选取一个膦催化共轭二烯与α,β-不饱和酮的[4+2]环加成反应为研究对象, 通过密度泛函理论计算、表征反应的详细机制. 总反应包含的四个基元步骤依次为偶极离子形成、分子间亲核加成、分子内环化和膦配体解离. 活化自由能垒的计算值为84.4 kJ/mol, 总反应的自由能变的计算值为–18.8 kJ/mol. 当使用手性膦催化剂时, 计算出的反应机理和动力学参数与实验观测的对映异构选择性相符, 并且揭示了立体选择性的根源是空间位阻导致过渡态的扭转张力增大, 从而不利于次要对映异构体的形成. 最后, 设计了四种二烯底物, 分别考察了它们与膦催化剂形成的偶极离子中间体, 表明底物上的2-酯基对反应活性和位置选择性起至关重要的影响, 而1-酯基的作用可能不重要. 研究成果可以为优化实验条件和设计新反应提供理论指导.

Organophosphine-catalyzed cycloaddition reaction provides an efficient method for the construction of valuable heterocycles. In this article, density functional theory calculations were performed on the mechanism of a phosphine-catalyzed [4+2] cycloaddition between conjugated dienes and enones reported recently. The overall reaction consisted of four sequential processes, namely the formation of the zwitterionic intermediate, intermolecular nucleophilic addition, intramolecular cyclization, and removal of the organophosphine. The activation free-energy barrier was estimated to be 84.4 kJ/mol, and the overall free-energy change was computed to be –18.8 kJ/mol. For the asymmetric variant of the reaction, the predicted enantioselectivity results were consistent with experimental findings, and what’s more, a distortional strain model was proposed to understand the observed enantioselectivity. Lastly, the substituent effects concerning the diene substrate were explored, which revealed that an ester group on the C(2) position would exert a much stronger influent on the reactivity than that on the C(1) position. The conclusions drawn in this work can help organic chemists to optimize experimental conditions and design new reactions.