Catalytic alpha-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation
This study reports the catalytic deracemization of ketones bearing stereocenters in the alpha-position in a single reaction via deprotonation, followed by enantioselective protonation. The principle of microscopic reversibility, which has previously rendered this strategy elusive, is overcome by a photoredox deprotonation through single electron transfer and subsequent hydrogen atom transfer (HAT). Specifically, the irradiation of racemic pyridylketones in the presence of a single photocatalyst and a tertiary amine provides nonracemic carbonyl compounds with up to 97% enantiomeric excess. The photocatalyst harvests the visible light, induces the redox process, and is responsible for the asymmetric induction, while the amine serves as a single electron donor, HAT reagent, and proton source. This conceptually simple light-driven strategy of coupling a photoredox deprotonation with a stereocontrolled protonation, in conjunction with an enrichment process, serves as a blueprint for other deracemizations of ubiquitous carbonyl compounds.
Zhang, Chenhao, Anthony Z. Gao, Xin Nie, et al. 2021. "Catalytic α-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation." Journal of the American Chemical Society 143(33): 13393-13400.
American Chemical Society
Journal of the American Chemical Society
Chemistry and Biochemistry
Silyl enol ethers, Transition-metal catalysis, Ketene disilyl acetals, Dynamic resolution, Bronsted acid, Racemate