Recent advances in catalytic α-deuteration of carbonyl compounds

Deuterium-labeled compounds are increasingly important in synthetic chemistry, pharmaceutical science, and materials research owing to the unique effects of isotopic substitution on molecular properties and metabolic stability. Among the available labeling strategies, catalytic hydrogen–deuterium (H/D) exchange at the α-position of carbonyl compounds has emerged as a direct and atom-economical approach for preparing valuable deuterated building blocks. Although early studies primarily focused on relatively acidic substrates such as ketones, recent advances have expanded the scope of this transformation to include amino acids, esters, amides, nitriles, and carboxylic acids. These developments have been enabled by diverse catalytic approaches, including base catalysis, Lewis acid activation, transition-metal catalysis, biocatalysis, electrochemical methods, and frustrated Lewis pair catalysis. Subsequent studies extended these methods from simple model substrates to the late-stage deuteration of pharmaceuticals, natural products, and functional materials. This mini-review highlights recent advances in catalytic α-deuteration of carbonyl compounds, organized by substrate class, with emphasis on reaction design and substrate scope. Remaining challenges and future opportunities, including chemoselective and stereoselective deuteration of less activated substrates, are also discussed.