Catalytic alpha-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation

Abstract

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.

Publisher

American Chemical Society

Publication Date

8-25-2021

Publication Title

Journal of the American Chemical Society

Department

Chemistry and Biochemistry

Document Type

Article

DOI

https://dx.doi.org/10.1021/jacs.1c06637

Keywords

Silyl enol ethers, Transition-metal catalysis, Ketene disilyl acetals, Dynamic resolution, Bronsted acid, Racemate

Language

English

Format

text

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