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

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.