Advances in photocatalytic deracemization of sp3-hybridized chiral centers via hydrogen atom transfer

Abstract

The enantioselective separation of racemate, particularly those containing C(sp³)-H bonds knowns for their high bond dissociation energies and significant polarity, presents a significant challenge in pharmaceutical synthesis. Recent advances have witnessed the fusion of photocatalysis with hydrogen atom transfer (HAT) methodologies, marking a notable trend in synthesis of chiral molecules. This technique uses the excitation of a catalyst to activate substrates, enabling the selective isomerization of chiral centers containing C(sp³) configurations. This process distinctively facilitates the direct activation of the C(sp³)-H bond in targeted reagents. This review systematically discusses the photocatalytic isomerization of various chiral molecule featuring C(sp³)-H centers, capable of undergoing deracemization through two primary HAT mechanisms: direct and indirect pathways. From the perspective of synthetic organic chemistry, this field has progressed towards the development of isomerization strategies for molecules that incorporate an activating group at the α-position adjacent to the C(sp³) chiral center. Moreover, it covers methodologies applicable to molecules characterized by specific C-C and C-S bond configurations. The integration of photocatalysis with HAT technology thus provides valuable strategies for the synthesis of enantiopure compounds with enhanced selectivity and efficiency.