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

Abstract

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.

Keywords

N-Heterocyclic carbene / DFT calculation / Dual catalysis / Asymmetric catalysis / Organocatalysis / Reaction mechanisms

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH