An efficient deuteration process of α-C-H bonds in various carbonyl-based pharmaceutical compounds has been developed. Catalytic reactions are initiated by the action of Lewis acidic B(C6F5)3 and D2O, converting a drug molecule into the corresponding boron-enolate. Ensuing deuteration of the enolate by in situ-generated D2O+-H then results in the formation of α-deuterated bioactive carbonyl compounds with up to >98% deuterium incorporation.