About the Talk:

The beneficial effects of fluorine substitution on the ADME properties of drugs has been widely recognized and its presence in pharmaceuticals and agrochemicals has increased dramatically due to the development of reagents for facile fluorination and trifluoromethylation. Conversely, the pentafluorosulfanyl (–SF₅) group remains underexplored due to the challenges of working with traditional gaseous and highly toxic –SF₅ precursors. The –SF₅ group possesses both high electronegativity and high lipophilicity, has high thermal and hydrolytic stability, and has shown enhanced pharmacological properties of drugs when compared to trifluoromethyl substituted analogs. Current access to aryl–SF₅ compounds is limited mainly to the simple thiophenols and derivatives amenable to the harsh oxidative-fluorination conditions necessary to generate the –SF₅ group. Recent efforts have realized the ability of phenothiazine photocatalysts to reduce nontoxic SF₆ to form a SF₅ radical and fluoride anion after mesolytic cleavage. Ultimately, the photolytically generated SF₅ radical was only shown to add anti-markovnikov to styrenes. The development of an easy-to-handle SF₅ precursor that undergoes reversible photo-promoted homolysis may help spur the development of pentafluorosulfanylation methodologies. To that end, development of a competent radical trap in conjunction with a N-arylphenothiazine photocatalyst may allow for the reduction of SF₆ and subsequent trapping of the generated SF₅ radical to create a stable, photocleavable SF₅ proradical reagent.