Fluorine Double Take

As fluorine chemistry has evolved by leaps and bounds over the past decade, the advances have come hand in hand with the introduction of easier-to-use and more versatile fluorinating reagents. In a new example, Abigail G. Doyle of Princeton University led a team that created 2-pyridinesulfonyl fluoride, or PyFluor, a mild-acting and thermally stable deoxyfluorinating reagent (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b06307). PyFluor replaces alcohol groups with fluorine and has a combination of selectivity, safety, and cost that surpasses that of old standards such as diethylaminosulfur trifluoride (DAST) and complements newcomer sulfur fluoride reagents such as XtalFluor and Fluolead. The researchers show it’s useful in making ¹⁸F-labeled compounds for PET imaging. In another example, Qilong Shen, Long Lu, and coworkers at Shanghai Institute of Organic Chemistry have reported N-di­fluoromethylthiophthalimide as a reagent for incorporating the difluoromethylthio group, –SCF₂H, into molecules under mild conditions (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b03170). Chemists who develop pharmaceuticals and pesticides have become enamored with the –SCF₃ group because it’s one of the most lipophilic functional groups known. The Shanghai team’s difluoro version offers additional flexibility in tuning the properties of boronic acids, alkynes, indoles, and more.