Cody Ross Pitts

The first assortment of achiral pentafluorosulfanylated cyclobutanes (SF 5 ‐CBs) are now synthetically accessible through strain‐release functionalization of [1.1.0]bicyclobutanes (BCBs) using SF 5 Cl. Methods for both chloropentafluorosulfanylation and hydropentafluorosulfanylation of sulfone‐based BCBs are detailed herein, as well as proof‐of‐concept that the logic extends to tetrafluoro(aryl)sulfanylation, tetrafluoro(trifluoromethyl)sulfanylation, and three‐component pentafluorosulfanylation reactions. The methods presented enable isolation of both syn and anti isomers of SF 5 ‐CBs, but we also demonstrate that this innate selectivity can be overridden in chloropentafluorosulfanylation; that is, an anti ‐stereoselective variant of SF 5 Cl addition across sulfone‐based BCBs can be achieved by using inexpensive copper salt additives. Considering the SF 5 group and CBs have been employed individually as nonclassical bioisosteres, structural aspects of these unique SF 5 ‐CB “hybrid isosteres” were then contextualized using SC‐XRD. From a mechanistic standpoint, chloropentafluorosulfanylation ostensibly proceeds through a curious polarity mismatch addition of electrophilic SF 5 radicals to the electrophilic sites of the BCBs. Upon examining carbonyl‐containing BCBs, we also observed rare instances whereby radical addition to the 1‐position of a BCB occurs. The nature of the key C(sp 3 )−SF 5 bond formation step – among other mechanistic features of the methods we disclose – was investigated experimentally and with DFT calculations. Lastly, we demonstrate compatibility of SF 5 ‐CBs with various downstream functionalizations.