The Origin of Stereoselectivity in Dual Transition‐Metal/NHC Asymmetric Catalysis: A Competitive Induction Model

Comprehensive Summary The origin of a transformation's stereoselectivity is one of the core issues in asymmetric catalysis. Herein, we propose a general competitive induction model for predicting stereoselectivity in dual transition‐metal‐NHC asymmetric catalysis. This model is demonstrated to explore the origin of stereoselectivity for the asymmetric synthesis of spirooxindoles by Cu(I)/NHC‐catalysed [3+3] annulation. Computational studies suggest a mechanism involving deprotonation, Brønsted‐acid‐assisted decarboxylation, nucleophilic addition, cyclic esterification, and protonation. Our studies suggest that nucleophilic addition is the reversible stereocenter‐generating step, while subsequent irreversible cyclic esterification is the stereoselectivity‐determining step. The metal‐coordinated chiral NHC ligand and the NHC organocatalyst work together to induce chirality in the stereocenter‐generating step. In the subsequent stereoselectivity‐determining step, the NHC ligand is innocent due to its long distance from the reaction site. Thus, the stereoselectivity is fully determined by the NHC organocatalyst. This constitutes a significant difference from the widely proposed synergistic induction model. This competitive induction model elucidates how the two chiral sources govern stereoselectivity in the stereocenter‐generating and stereoselectivity‐determining steps, providing valuable insights for the rational design of cooperative asymmetric catalyst systems.