Cobalt-catalyzed dehalogenative deuterations with D2O

ABSTRACT The regioselective incorporation of deuterium to organic skeletons has gained ever-growing attention among scientific community. Herein, we present a robust and general protocol for site-specific deuteration through the cobalt catalyzed dehalogenative process. Using D2O as the economical deuterium reagent, we achieved excellent substrate compatibility across a wide collection of organohalides or pseudo-halides, such as aryl, alkenyl, benzyl, allyl, or alkyl halides and propargyl acetates. Preliminary experimental evidences and related DFT calculation are also presented to support a mechanistic scenario involving a Co(I)-C(III)-Co(I) cycle. The generality and potential utilization of this moisture-insensitive catalysis have also been demonstrated by the selective deuterodehalogenation of drug-like candidates, concise synthesis of D-labeled pharmaceutical molecule, as well as the stepwise hydrogen isotope exchange of bioactive compounds.