Stereogenic and Conformational Diversity in Multicomponent Ir-Catalyzed Borylation of Arenes: Unveiling the Origin of Enantioselectivity by Conformational Sampling.

To date, multicomponent transition-metal-catalyzed asymmetric reactions have led to pivotal breakthroughs in modern catalysis. However, investigations on the mechanism of these reactions are inherent challenges due to the coeffect of the complicated stereostructures and multiple noncovalent interactions. Here, we proposed a stepwise computational workflow combining density functional theory (DFT) calculations and molecular dynamics (MD) simulations to investigate a multicomponent Ir-catalyzed asymmetric borylation of arenes induced by chiral cations. Based on a definite rate-determining step investigated by DFT calculations, we employed MD simulations with constrained harmonic potential for coordinate bonds to completely sample the conformations of enantioselectivity-determining transition-state ensembles. Interestingly, results reproduce well the experimental enantioselectivity (ee value) and clearly reveal that both quantity and energy of conformations are responsible for the enantioselectivity. Systematical analysis on the conformations suggests that the advantages of