Site-Selective and Late-Stage Deuteration of (Hetero)arenes with Supported Iridium Nanoparticles

Deuterated compounds have emerged as critical tools across diverse research areas, including pharmaceuticals, where deuterium incorporation can modulate the absorption, distribution, metabolism, and excretion (ADME) prop-erties of drugs. In this study, we report the development of a novel hydrogen/deuterium (H/D) exchange catalyst based on supported iridium nanoparticles, which enables selective deuteration of arenes and heteroarenes under mild conditions. Using C6D6 as the deuterium source, our catalytic system achieves high chemo- and regioselectivity, avoiding the common side reactions such as hydrogenation and dehalogenation observed with traditional heteroge-neous catalysts. Notably, the deuteration occurs selectively at the para- and meta-C(sp2)–H bonds, leaving ortho C(sp2)–H and C(sp3)–H bonds intact, and exhibits broad functional group tolerance, including with ketones, amides, alkenes, aryl ethers, and acidic protons. The heterogeneous nature of the catalyst was confirmed via filtration and mercury drop tests. This work presents a novel catalytic system for regioselective deuteration of complex molecules, offering complementary site selectivity to existing homogeneous and heterogeneous methods and the possibility to be used in the late-stage deuteration of pharmaceuticals.