Bench-stable reagents for modular access to persulfuranyl scaffolds

The vast expanse of chemical space offers limitless possibilities for medicinal chemists, particularly in discovering novel scaffolds and functional groups with drug-like properties. However, the widespread adoption of these functional groups is often limited by their synthetic accessibility and functionalization. Among these functional groups, the pentafluorosulfanyl group has been long considered a potential (bio)isostere for tert-butyl and trifluoromethyl groups, yet limitations in methodologies have constrained access to it. To bridge this gap, we have developed a general pentafluorosulfanylation platform that employs bench-stable solid reagents to generate SF₅ radicals via a decarboxylation and β-scission sequence. This strategy enables a variety of operationally simple transformations, expanding the accessibility of SF₅-containing molecules. Notably, this reagent design is also adaptable to other persulfuranyl groups, such as trifluoromethyl tetrafluorosulfanyl and aryl tetrafluorosulfanyl groups. Taken together, generating an armamentarium of these stable reagents and practitioner-friendly chemical methodologies will enable the synthesis of challenging and biologically relevant sulfur(VI) chemical entities in an expedient manner.