Late-Stage C–HDeuteration of (Hetero)Arenesvia Deuterium-Bonding Enhanced Rhenium Catalysis

We describe in this work a Re₂O₇-catalyzed nondirected C–H deuteration of arenes and heteroarenes. This process was facilitated via a network of deuterium bonds with AcOD that also serves as an inexpensive deuterium source. With this operationally facile protocol, various arenes could be deuterated with a high level of isotope incorporation. Compared to other acid-mediated C–H deuterations, rhenium catalysis makes weak acid AcOD a powerful deuterium reagent for a broad substrate scope and at the same time shows significantly improved functional group tolerance due to its relatively low acidity, which was exemplified in the late-stage isotopic labeling of various pharmaceuticals and biologically active molecules. ¹H NMR and DFT calculations were carried out to study the role of deuterium bonding.