Triphosgene/KF-mediated acyl fluoride synthesis via in situ fluoro(chloro)phosgene

Abstract

The transformation of carboxylic acids into acyl fluorides via triphosgene-mediated deoxyfluorination utilizing inexpensive potassium fluoride (KF) has been achieved. This method affords a diverse range of acyl fluorides in high yields and exceptional purity. Analysis using ¹⁹F NMR spectroscopy reveals that fluorophosgene and chlorofluorophosgene, generated in situ, serve as the reactive intermediates crucial to the conversion process. The protocol exhibits excellent functional group tolerance, enabling late-stage modification of biologically relevant compounds, and is scalable for both lab and industrial use. Acyl fluorides also proved valuable as precursors for amides, organic intermediates, and fluorine donors.