Site-Selective and Late-Stage Deuteration of (Hetero)arenes with Supported Iridium Nanoparticles
Chengbo Yao, Christophe Copéret
Abstract
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) properties of drugs. In this study, we report the development of a new hydrogen/deuterium (H/D) exchange catalyst based on supported iridium nanoparticles that enables selective deuteration of arenes and heteroarenes under mild conditions. Using C 6 D 6 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 heterogeneous catalysts. Notably, the deuteration occurs selectively at the para - and meta -C(sp 2 )–H bonds, leaving ortho -C(sp 2 )–H and C(sp 3 )–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 new catalytic system for regioselective deuteration of complex molecules, offering complementary site selectivity to existing homogeneous and heterogeneous methods and the possibility of being used in the late-stage deuteration of pharmaceuticals.