71. Light-Driven Crystallization-Induced Dynamic Resolution of Amines

Jonathan M. Meinhardt, Diane D. Kim, Emily J. Wu, Philip R. D. Murray, Daniel P. Walker, Robert R. Knowles

J. Am. Chem. Soc. 2025, 147, 25851–25857. DOI: 10.1021/jacs.5c07676

https://pubs.acs.org/doi/10.1021/jacs.5c07676

Abstract: We report a method for the dynamic resolution of racemic amines enabled by catalytic photoredox-mediated racemization coupled to in situ diastereomeric crystallization. In this design, an excited-state iridium chromophore and an achiral thiol cocatalyst mediate the racemization of α-chiral amines under mild, redox-neutral conditions. In the presence of commercially available chiral resolving acids, the desired amine enantiomer is continually precipitated from solution as an insoluble diastereomeric salt. We demonstrate the utility of this method across several structurally distinct families of secondary and tertiary amines with high yields and high levels of enantioselectivity. Given the widespread importance of α-stereogenic amines in the synthesis of fine chemicals, we anticipate that this approach may find further applications that streamline the preparation of these valuable chiral compounds.