To date, about 20% of the commercial pharmaceuticals are fluorine-containing pharmaceuticals. Acyl fluorides are key intermediates in organic synthesis with a wide range of applications including the syntheses of amides, esters, peptides, and dry fluoride salts. However, previously established approaches often require toxic, unstable additives and harsh reaction conditions. Herein, we present a chemoselective deoxyfluorination reaction of carboxylic acids by using KF and highly electron-deficient fluoroarenes under mild conditions, giving acyl fluorides in moderate to excellent yield with a wide range of functional group compatibility. Directly utilizing KF for deoxyfluorination of carboxylic acids provides an alternative and quick pathway to access acyl fluorides that are compatible with late-stage fluorination, high temperature reaction, and facile target compound purification.
Mao, Siyu, "Deoxyfluorination of carboxylic acids with KF and highly electron-deficient fluoroarenes" (2021). IdeaFest. 405.