UC Davis

This dissertation is comprised of five published bodies of work pertaining to strain-release pentafluorosulfanylation. Until recently, extant methods to introduce the pentafluorosulfanyl functional group to aliphatic organic molecules have solely focused on the addition of a pentafluorosulfanyl-centered radical to a non-aromatic π-bond. The major innovation that enabled the entirety of the work explored in this dissertation was the addition of the SF5 radical intermediate to strained σ-bonds. Following the introductory chapter, Chapter 2 details the advent of strain-release pentafluorosulfanylation. That is, a method for the formal chloropentafluorosulfanylation with the canonical strain-release reagent – [1.1.1]propellane – was developed, creating access to a novel “hybrid bioisostere.” In Chapter 3, this synthetic logic is extended to the exploration of a curious polarity-mismatched case of formal chloropentafluorosulfanylation of sulfone- and carbonyl-substituted bicyclo[1.1.0]butanes. The operative mechanisms were of fundamental interest, paving the way for computational investigation and mechanistic experiments. In Chapter 4, the propensity of bicyclo[1.1.0]butanes (BCBs) to act as “spring-loaded” electrophiles is leveraged to create divergent access to complementary OCF3- and OSF5-containing cyclobutane building blocks. Chapter 5 reports a rare instance heteroatom–SF5 bond formation employing 3- aryl azabicyclo[1.1.0]butanes as substrates. The resulting pentafluorosulfanylated azetidines were then evaluated as lipophilic bioisosteres for small sulfonamides through in vitro ADME assays. Finally, Chapter 6 chronicles the application of a tetrafluorosulfanyl(aryl)bicyclopentane in the context of materials design and thermosalient crystals. Upon cooling a single crystal of this compound, the sample violently shattered into small fragments. Extensive mechanistic studies revealed that the phase transition of a trace impurity concomitant with a phase transition at the interface with the bulk material leads to the observed destruction.