Visible-light-mediated deuteration of aldehydes with D2O via polarity-matched reversible hydrogen atom transfer

Abstract

Hydrogen/deuterium exchange at the formyl groups of aldehydes is the most direct way to synthesize deuterated aldehydes, which are of interest for labeling studies and drug discovery. Herein, we report a mild, general protocol for visible-light-mediated metal-free deuteration of aldehydes in D 2 O with synergistic photoredox and thiol catalysis. The protocol is highly efficient, has a broad substrate scope, and shows excellent functional group tolerance and selectivity, all of which make it suitable for generating libraries of deuterated compounds. The efficient deuteration was attributed to a photoredox-catalyzed polarity-matched reversible hydrogen atom transfer reaction between the aldehydes and the thiol. • Hydrogen/deuterium exchange at the formyl groups of aldehydes. • Deuterated aldehydes are of particular interest for labeling studies and drug discovery. • Photoredox-catalyzed polarity-matched reversible hydrogen atom transfer. • Synergistic photoredox and thiol catalysis.