Deuteration and Tritiation of Pharmaceuticals by Non-Directed Pd 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, D2O, as the only solvent 34 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 an aromatic drug scaffold by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.