Unraveling the Molecular Origin of the Unprecedented ortho-Chloride Effect in Cobalt-Catalyzed Asymmetric Hydrogenation of 1,1-Diarylethenes.

The molecular origin of the unusual ortho-chloride effect in cobalt-catalyzed asymmetric hydrogenation of 1,1-diarylethenes has been investigated using density functional theory. The complete catalytic cycle, including alkene coordination, alkene insertion, hydrogen activation, and catalyst regeneration, was elucidated on the relevant spin surfaces. The calculations identify alkene insertion into the Co-H bond via TS1 as the enantiodetermining step, whereas catalyst regeneration is the turnover-determining step. The preferred Si-face hydride transfer is favored by 3.79 kcal/mol, corresponding to a predicted 99.6% enantiomeric excess, in excellent agreement with the experimentally observed more than 90% ee. Activation strain, AIM, NCI, and NBO analyses reveal that reduced structural distortion together with enhanced noncovalent and donor-acceptor interactions stabilizes the transition state leading to the S enantiomer. Systematic investigation of substituent effects demonstrates that only the ortho-chloro substituent provides the optimal energetic balance, whereas meta- and para-substitution or replacement by other ortho substituents substantially diminishes enantioselectivity. These findings provide the first molecular-level explanation of the ortho-chloride effect and offer guiding principles for designing highly enantioselective cobalt catalysts.