Deracemization of C(sp3)–H Arylated Carbonyl Compounds via Asymmetric Ion-Pairing Photoredox Catalysis

Abstract

Deracemization of C(sp³)–H arylated carbonyl compounds faces limitations in terms of substrate scope. Through the photoactivation of the aryl group and the stereocontrol of the generated arene radical cation via asymmetric ion-pairing catalysis, we are able to achieve deracemization of carbonyl compounds arylated at both enolizable and unenolizable stereocenters. A diverse range of α-, β-, and γ-aryl ketones and esters, including natural products and medicinal derivatives, can be effectively converted into their enantiomers with high enantioselectivity. Mechanistic investigations through combined experimental and computational studies suggest that the reaction involves single-electron oxidation of electron-rich aryl groups, followed by a kinetic resolution of the resulting radical cation intermediates by the chiral phosphate anion. Deprotonation is identified as the stereodetermining step, while stereoselective back electron transfer and triplet-state quenching of ³ Mes-Acr₁⁺* may also affect the enantioselectivity at the photostationary state.