Nickel-catalyzed reductive coupling of 2-pyridyl esters with unactivated alkyl chlorides: a universal synthesis of aryl-alkyl and dialkyl ketones via dynamic halide exchange.

Direct synthesis of ketones via a nickel-catalyzed reductive coupling between aryl, 1°, 2°, 3°-alkyl 2-pyridyl esters and unactivated 1°, 2°-alkyl chlorides has been reported. This approach provides a highly efficient catalytic system to synthesize aryl-alkyl and dialkyl ketones in moderate to excellent yields with good functional group tolerance from easily accessible starting materials. Mechanistic studies reveal that a TBAI-mediated dynamic halide exchange process maintains a controlled low concentration of alkyl iodides, balancing the reactivity and cross-selectivity of alkyl chlorides.