Aryl Halide Carboxylation via Decarboxylative Metal–Halogen Exchange

A unique mode of metal-halogen exchange is reported for the carboxylation of aromatic halides. The process is mediated by the potassium salt of a commercially available carboxylic acid, which acts as the source of CO2 and metalating agent. The procedure demonstrates that readily available, bench-stable carboxylic acid salts can generate metalating agents in situ for metal-halogen exchange, thus avoiding sensitive and hazardous organometallics. The carboxylation proceeds under mild conditions, shows broad substrate scope and avoids specialized apparatus such as pressurized containers or strictly inert conditions. Application to the carbon isotope labeling of biologically relevant compounds is also reported, including a late-stage carbon isotope exchange. Experimental and computational studies support our proposed mechanism of decarboxylative metal-halogen exchange in which the metalating agent and CO2 are generated in situ from the carboxylate salt.