State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering , Nankai University , Tianjin 300071 , China.
Center of Basic Molecular Science, Department of Chemistry , Tsinghua University , Beijing 100084 , China.
J Org Chem. 2018 Mar 16;83(6):3333-3338. doi: 10.1021/acs.joc.8b00469. Epub 2018 Mar 7.
The merger of the common photoredox catalyst Ru(bpy)Cl with an imidazolidinone organocatalyst by MacMillan et al. has enabled a series of highly enantioselective α-functionalizations of aldehydes, a landmark discovery in photoredox organocatalysis. Herein, we present the theoretical investigation into the origin of enantioselectivity in asymmetric radical additions to the MacMillan imidazolidinone enamines, the key stereocontrolling step in photoredox organocatalysis of asymmetric α-functionalizations of aldehydes. The calculations reveal a hidden but crucial role of E-cis enamine in enantiocontrol. The enantioselectivity in the radical additions is mainly determined by steric effects. A model based on the pseudo C-symmetric arrangement of the methyl and tert-butyl moieties on the catalyst is proposed. This rationalizes the stereoselective outcome of these reactions and provides a good model to understand MacMillan's imidazolidinone/photoredox dual catalysis. The insights obtained from this study should be valuable in future efforts toward the design and development of new enantioselective catalytic radical reactions.
由 MacMillan 等人将常见的光氧化还原催化剂 Ru(bpy)Cl 与咪唑烷酮有机催化剂融合，实现了一系列高度对映选择性的醛的 α-官能化，这是光氧化还原有机催化中一个具有里程碑意义的发现。在此，我们对不对称自由基加成到 MacMillan 咪唑烷酮烯胺中的对映选择性起源进行了理论研究，这是不对称醛α-官能化的光氧化还原有机催化中的关键立体控制步骤。计算揭示了 E-顺式烯胺在对映控制中隐藏但至关重要的作用。自由基加成的对映选择性主要由空间效应决定。提出了一个基于催化剂上甲基和叔丁基部分的拟 C-对称排列的模型。这合理化了这些反应的立体选择性结果，并提供了一个很好的模型来理解 MacMillan 的咪唑烷酮/光氧化还原双重催化。本研究获得的见解对于未来设计和开发新的对映选择性催化自由基反应应该是有价值的。
