Few elements can rival the rise to prominence that fluorine has experienced in the past several decades.  Both the pharmaceutical and agrochemical industries have utilized organofluorine compounds due to their enhancements of several physical properties, such as acidity, conformation, lipophilicity and metabolic stability.  In order to facilitate this growth, several synthetic methods have been developed for fluorine incorporation.  Deoxyfluorination, one of the most prominent methods, requires a reagent that converts oxygen-based functional groups into a viable leaving group in order for the substitution to occur.  Despite a variety of reagents available, most still struggle with slow reaction times, with some of the most popular requiring reaction times in the hours to days timescale.  To accelerate deoxyfluorination, we have developed a novel class of compound: sulfone iminium fluorides (SIFs).   A tunable synthesis is described, which has enabled the creation of a small library of highly reactive SIFs with a variety of substituents, offering further alterations of stereoelectronic properties.  These reagents can effectively engage aliphatic alcohols and carboxylic acids in rapid deoxyfluorination, producing alkyl fluorides and acid fluorides in good yields in just five minutes, representing some of the fastest fluorination rates to date.

Development of highly tunable reagents for rapid deoxyfluorination

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.