Deuteration and Tritiation of Pharmaceuticals by Non‐Directed Palladium‐Catalyzed C−H Activation in Heavy and Super‐Heavy Water

Abstract

Abstract 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.