Copper-catalyzed deuterodehalogenation of aryl halides

Abstract

There is growing potential and interest in the development of precise and practical deuterium labelling methodologies using an easy-handling deuterated source for alkylarenes and methylarenes. Here we report a heterogeneous copper catalyst that enables dehalogenative deuteration of aromatic halides using D₂O as a deuterium source. This methodology showed a broad substrate scope and good functional group tolerance. Using inexpensive and easy-handling D₂O as the deuterium source under mild conditions allows for the preparation of deuterated building blocks, representative drugs and late-stage labelling of bioactive molecules with high deuterium incorporation. In this reaction, DMF not only is a solvent, but also a precursor of CO surrogate and a base, which is essential to the deuterium incorporation. This methodology represents a practical and scalable deuteration (demonstrated by the synthesis of deuterium labelling products on the 50 ​g) and the air- and water-stable copper catalyst straightforwardly enables efficient labelling.