Bicyclic Guanidine-Catalyzed Asymmetric Cycloaddition Reaction of AnthronesBifunctional Binding Modes and Origin of Stereoselectivity

We report a computational analysis of the [5,5] bicyclic guanidine-catalyzed asymmetric cycloaddition reaction of anthrones. Based on extensive conformational search of key intermediates and transition states on the potential energy surface and density functional theory calculations, we studied five plausible binding modes between the guanidine catalyst and substrates for this reaction. Our results indicate that the most favorable pathway is a stepwise conjugate addition-Aldol sequence via the dual hydrogen-bond binding mode. The predicted level of enantioselectivity is in good agreement with experimental values. Trends in variation of substrates and catalysts have also been reproduced by our calculations. Decomposition analysis revealed the significance of aromatic interactions in stabilizing the key enantioselectivity-determining transition state structures.本研究报道了[5,5]双环胍催化蒽酮不对称环加成反应的计算分析工作。通过对势能面上关键中间体与过渡态的大规模构象搜索，并结合密度泛函理论（Density Functional Theory）计算，本研究针对该反应中胍催化剂与底物间的五种可行结合模式进行了系统探究。研究结果表明，最优势的反应路径为经由双氢键结合模式的分步共轭加成-羟醛缩合序列。预测所得的对映选择性水平与实验值吻合良好。底物与催化剂的构效变化趋势也通过本次计算得到了重现。分解分析揭示了芳香相互作用在稳定关键对映选择性决定过渡态结构过程中的重要意义。