Deuterium Installation in Contemporary Chemistry: New Tools and Strategies

ABSTRACT Deuterium, the stable heavy isotope of hydrogen, has become an indispensable element of modern chemical research due to the primary kinetic isotope effect arising from the enhanced stability of C–D bonds. The strategic incorporation of deuterium has found significant applications in medicinal chemistry through the “deuterium switch” approach to improve metabolic stability of drug candidates, exemplified by the FDA‐approved drug deutetrabenazine, while isotopic labelling continues to play a critical role in mechanistic investigations. This review provides a comprehensive and critical evaluation of recent advances in deuterium incorporation strategies, with particular emphasis on late‐stage functionalization enabled by catalytic hydrogen‐isotope exchange and site‐selective C–H activation using economical and readily available deuterium sources. Diverse catalytic platforms, including transition metal catalysis (Ni, Cu, Zn, Rh, Pd, Sm, Ir, and Fe), as well as emerging organocatalytic, photoredox, and electrosynthetic methodologies, are systematically discussed alongside a broad spectrum of deuterium sources such as D 2 O, D 2 , CD 3 OD, CDCl 3 , AcOD, CD 3 COOD, CF 3 OD, CD 3 OTs, NaCOOD, CD 3 CN, d 1 ‐HFIP, DMSO‐d 6 , and t BuND 2 . By showcasing the versatile installation of deuterium across diverse molecular architectures, this review aims to establish a unifying conceptual framework that will stimulate further innovation in deuterium chemistry and facilitate the discovery of new reactivity paradigms.