Deuteration and tritiation of pharmaceuticals by non-directed palladium-catalyzed C-H activation in heavy and super-heavy water

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D${}_2$O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non-directed homogeneous Pd-catalysis for H/T exchange on three different pharmaceuticals by using T${}_2$O as isotopic source, demonstrating the applicability to the synthesis of radiotracers. (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH)