Recent Advances in Transition Metal-Catalyzed Multideuteration of (Hetero)Arenes via Hydrogen Isotope Exchange

Deuteration has gained a prominent role as a powerful method for investigating kinetic isotope effects in chemical reactions. Recent studies show that deuteration can significantly alter the pharmacokinetic and toxicological profiles of drug molecules, thereby enhancing their therapeutic efficacy. As a result, deuteration is being increasingly integrated into pharmaceutical development. At the same time, introducing deuterium into organic electronic materials helps to reduce high-frequency molecular vibrations, thus broadening the range of applications of organic materials, traditionally dominated by inorganic components. Since the approval of the deuterated drug deutetrabenazine in 2017 and the commercialization of deuterated emissive materials for organic light-emitting diodes, multideuteration technologies have advanced considerably. Various strategies utilizing both rare and earth-abundant metals to achieve efficient multideuteration have been reported. This review examines recently developed metal catalysts for multiple deuteration, discusses current challenges in deuteration methods, and explores future opportunities in this rapidly evolving field.