Overcoming a Radical Polarity Mismatch in Strain-Release Pentafluorosulfanylation of [1.1.0]Bicyclobutanes: An Entryway to Sulfone- and Carbonyl-Containing SF 5 -Cyclobutanes.

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.