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 tert-butyl group
substitution at the meta position of the outer chiral
cation for enantioselective C–H borylation do not arise from
steric repulsion of the tert-butyl group destabilizing
the unfavorable R-forming transition states but other
two factors: (i) the limited conformational freedom due to the bulky tert-butyl group and (ii) the dispersion interactions between
the tert-butyl group and the methyl group of the
Bpin ligand stabilize the S-forming transition state
more than R-one. This work underscores the fundamental
significance and importance of conformational space accessibility
and multiple noncovalent interactions for elucidating the origin of
asymmetry induction.