Pd-catalyzed deuteration of aryl halides with deuterium oxide.

Abstract

Late-stage deuteration of aryl halides with deuterium oxide is a highly desirable but challenging transformation, primarily due to the difficulty of activating inert carbon-halogen bonds and the umpolung of deuterium oxide in the presence of various functional groups. To achieve this transformation, efforts have been made to develop photo-chemical, electro-chemical, or mechano-chemical strategies. However, these approaches often require specialized setups or activated substrates. Despite the well-known functional group tolerance of palladium catalysis, which makes it valuable in late-stage functionalization, a palladium-catalyzed deuteration of aryl halides with deuterium oxide has remained elusive. Herein, a deuteration reaction of aryl bromides, chlorides, and triflates with deuterium oxide has been developed, through palladium catalysis. Chemical equivalent amount of D₂O is required for inert substrates like aryl chlorides. The reaction features high functional group tolerance, making it suitable for late-stage deuteration.