Divergent Reactivity toward Decarboxylative Protonation or Oxidation via Single-Component Organocatalysis

Abstract Decarboxylative protonation/deuteration provides a powerful strategy for removing carboxylic acid handles and installing C–H/D bonds. However, existing catalytic methods typically rely on separate components to conduct the necessary proton-transfer, electron-transfer, and hydrogen-atom-transfer steps, restricting substrate scope and scalability. Herein we report a single-catalyst platform for decarboxylative protonation/deuteration that is broadly tolerant of carboxylic acids and readily scalable to 100 mmol in flow. Diarylquinoline organocatalysts function simultaneously as the base, photo-oxidant, and hydrogen-atom donor, demonstrating an underexplored reactivity mode for photocatalysts in which reductive quenching occurs by facilitating C–H bond formation rather than conventional electron transfer processes. Mechanistic studies indicate that oxidation is achieved through proton-coupled electron transfer (PCET), resulting in high chemoselectivity for carboxylic acid activation. Hammett analysis reveals that catalyst electronics strongly influence the reaction rate, and an uncommon inverse kinetic isotope effect provides evidence for a turnover-limiting, hydrogen-bonded transition state. Finally, reactivity can be diverted toward decarboxylative oxidation to form carbonyl compounds simply by changing the reaction atmosphere, offering versatile synthetic control.