Palladium-catalyzed directly carbonylative synthesis of fluoro-substituted malonates from (fluoro)bromoacetates.

[Display omitted] • A mild and efficient palladium-catalyzed carbonylation procedure toward the preparation of (fluoro)malonate derivatives has been developed. • Various (fluoro)malonate compounds were prepared in good to excellent yields with broad functional group tolerance. • The reaction can be scaled-up and performed under atmospheric pressure. Traditional procedures toward 2-fluoromalonates tend to meet overfluorination. Herein, we describe a mild and efficient palladium-catalyzed carbonylative strategy for the synthesis of dialkyl 2-fluoromalonate derivatives avoided the mentioned challenges. By this new procedure, a range of malonates and difluoromalonate derivatives were prepared with good functional-group tolerance and excellent chemoselectivity. This procedure can also be applied in the late-stage carbonylation of various bioactive molecules. Furthermore, a low-pressure experiment and two scale-up reactions were performed smoothly in good to excellent yield. [ABSTRACT FROM AUTHOR]