Catalytic Hydrogen Isotope Exchange Reactions in Late-Stage Functionalization

Abstract The introduction of deuterium and tritium into molecules is of great importance in drug discovery. Many attempts have been made to develop late-stage hydrogen isotope exchange (HIE) reactions to avoid multistep syntheses using commercially available labeled precursors. In this review, we summarize recent progress in catalytic HIE reactions, with our main focus on their applications in the late-stage labeling of bioactive complex molecules and pharmaceuticals1 Introduction 2 Non-Transition-Metal-Catalyzed Hydrogen Isotope Exchange 2.1 Organocatalysis 2.2 Photoredox Catalysis 3 Transition-Metal-Catalyzed Hydrogen Isotope Exchang 3.1 Palladium 3.2 Ruthenium 3.3 Iridium 3.4 Other Metals 4 Summary