Leveraging electron donor-acceptor complexes for kinetic resolution in catalytic asymmetric photochemical synthesis.

Abstract

The formation of electron donor-acceptor (EDA) complexes has emerged as a powerful strategy for accessing valuable molecules. However, protocols for constructing enantio-enriched molecules are limited, typically relying on EDA complex formation between a substrate and an intermediate generated from a chiral catalyst along with another substrate. This approach facilitates the coupling of the resulting radical species, thereby enabling the controlled enantioselective formation of stereocentres. Here we introduce a kinetic resolution strategy that harnesses the formation of EDA complexes between a chiral catalyst and racemic feedstock. The key lies in the thermodynamic disparity of the chiral catalyst's interaction with the two enantiomers of the substrate, which is critical for enabling subsequent transformations under a kinetic control. We demonstrate that photochemical reactions involving racemic azaarene-functionalized tertiary alcohols and amines, together with a chiral phosphoric acid, yield enantio-enriched derivatives containing tertiary carbon stereocentres. The utility of this approach is further exemplified by synthesizing important azaarene variants featuring tertiary or secondary C-F bonds, as well as ethylene oxides.