Fluorine is a powerful atom that has become pivotal in the chemistry of drugs. The introduction of fluorine into biologically active molecules significantly affects its lipophilicity, solubility, acidity, and basicity leading to the modulation and/or increase in its binding affinity, pharmacokinetic properties, and bioavailability. One common way of introducing this unique element is through deoxyfluorination, where an oxygen functional group is substituted for fluorine. Carboxylic acids are an example of a functional group that is often targeted for deoxyfluorination, since a multitude of pharmaceuticals possess this moiety; successful deoxyfluorination of carboxylic acids generates acid fluorides. Given the increasing demand for fluorinated compounds, the synthesis of organofluoro-compounds industry has witnessed tremendous advancements in efforts to develop a broad range of reagents capable of deoxyfluorination. Previous conversions of carboxylic acids to acid fluorides relied on long reaction times and elevated temperatures with highly toxic reactants. To combat these issues, we have developed a novel class of deoxyfluorination reagent: sulfone iminium fluorides. This work introduces a tunable synthesis for these compounds while also demonstrating a superior, rapid deoxyfluorination (less than 5 minutes) for the conversion of carboxylic acids to acid fluorides.

Industry of fast deoxyfluorination: New sulfur and fluorine alliance and its application in the fluorination of carboxylic acids

ACS Spring 2022

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