Catalyst design in heterogeneous deuteration: recent advances and perspectives

Deuterium-labeled compounds have become indispensable across pharmaceutical research and development, analytical testing, and materials science, driving urgent demand for efficient deuteration methodologies. However, current synthetic routes are frequently constrained by high costs of deuterium sources, reliance on noble metal catalysts, and difficulties in catalyst recovery. In recent years, heterogeneous catalytic strategies using deuterium oxide as a low-cost deuterium source have attracted considerable attention, owing to their advantages in catalyst recoverability, operational simplicity, and scalability. This review provides a comprehensive overview of recent advances in heterogeneous catalysis for site-selective deuteration and perdeuteration, with a particular focus on catalyst design. We systematically examine the key factors that influence deuteration efficiency and site selectivity in deuteration reactions, including the metal active centers, supports, substrate structures, and reaction conditions. Special emphasis is placed on the distinct performance of noble-metal, non-noble-metal, and metal-free catalytic systems in site-selective deuteration, alongside the unique role of noble metals in perdeuteration. While noble metals have proven effective for both site-selective deuteration and perdeuteration, non-noble and metal-free systems are currently explored predominantly for site-selective deuteration. Future research directions include the development of low-loading noble-metal catalytic systems, functional additives and reaction media engineering, non-noble metal catalytic systems, mild catalytic deuteration with low-cost deuterium sources, mechanistic understanding and advanced in situ characterization, integration of machine learning for high-throughput screening, and scalability and industrial translation, which will become key areas of research in deuteration technology. This review is intended to provide practical guidance for the rational design of efficient, selective, and sustainable heterogeneous deuteration catalysts, thereby facilitating the broader adoption of deuterium labeling across the chemical and pharmaceutical industries.