Electroreductive deuteration of N-propynylamides to enamides

Abstract

Deuterium-labeled molecules play a crucial role in numerous areas, from medicinal chemistry to chemical biology, providing a unique opportunity to improve ADMET properties and study the biological fate of bioactive molecules. Herein, we present an electromigratory reductive deuteration of terminal alkynes to access a diverse array of enamides with more than 3 deuteriums incorporated per molecule, using CD₃CN as a deuterium source. The reaction proceeds under mild neutral conditions, does not require precious transition metals, and shows broad substrate scope with excellent E-selectivity. We envision that this on-demand high deuterium incorporation will provide considerable opportunities in therapeutics and biological research.