Chiral catalyst-controlled asymmetric ring-opening of epoxides represents an attractive approach for stereoselective synthesis, but typically limited to heteroatom-centered nucleophiles. We report an enantioselective reductive Csp<sup>3</sup>-Csp<sup>2</sup> coupling of styrene oxides and aryl halides via the merger of nickel and photoredox catalysis. This method provides facile access to chiral 2,2-diarylalcohols in high enantioselectivity from racemic epoxides via a stereoconvergent mechanism. Multivariate linear regression (MVLR) analysis with bioxazoline (BiOx) and biimidazoline (BiIm) ligands revealed that the electronic character of the ligands influences the enantioselectivity, as opposed to steric effects which are typically implicated in asymmetric induction. Further experimental and computational mechanistic studies provides support to the hypothesis that positional control of the transition states along the reaction coordinates is responsible for the electronic effects on enantioselectivity. This study highlights the use of statistical modeling to elucidate a non-intuitive structure-selectivity relationship and provides insight into the design of improved chiral ligands for stereoconvergent Ni cross-coupling.

Ni/photoredox-catalyzed enantioselective cross-electrophile coupling of styrene oxides with aryl halides: A data-driven approach to mechanistic understanding and ligand design

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.