UBC Theses and Dissertations

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UBC Theses and Dissertations

Investigations of one-pot synthetic transformations mediated by sulfuryl fluoride and thionyl fluoride Bolduc, Trevor G.


The development of mild, selective, efficient, and economical chemical transformations is a foundation of modern synthetic organic chemistry. These chemical processes may be utilized in the syntheses of pharmaceutical compounds, facilitating improved approaches to complex targets. Novel reagents are often created and studied during the development of these more effective protocols. This dissertation explores several synthetic applications of sulfuryl fluoride and thionyl fluoride as reagents in useful chemical processes. Little is known about the synthetic applications of thionyl fluoride, and the work presented herein includes some of the first investigations of this chemical as a reagent in synthetic organic chemistry. Chapter 2 describes the sulfuryl fluoride-mediated transformation of thiols to the corresponding 1,1-dihydrofluoroalkyl sulfide. The primary themes of the work outlined in this chapter include investigations into the chemoselectivity of the title reaction for thiols over other nucleophilic moieties, as well as an expansion of the scope of 1,1-dihydrofluoroalcohols. In Chapter 3, the kinetics of the one-pot sulfuryl fluoride-mediated activation and nucleophilic acyl substitution of carboxylic acids are explored using quantitative 1H and 19F nuclear magnetic resonance spectroscopy. The addition of a tetrabutylammonium halide salt additive as much as doubles the rate of formation of the intermediate acyl fluoride, yet there is no effect on the rate of consumption of this intermediate by the nucleophilic coupling partner. Contributions made to the substrate scope are further outlined in this chapter. Chapter 4 details a comprehensive study of several new synthetic applications of thionyl fluoride in the context of carboxylic acid activation. One-pot, column-free nucleophilic acyl substitutions and one-pot, mild reductions are described in this work. Activated esters, amides, and alcohols are all accessible via the corresponding acyl fluoride intermediate. Chapter 5 explores an expedited one-pot, thionyl-fluoride mediated conversion of sulfinic acids to the corresponding sulfonimidoyl fluoride, utilizing bench-stable and accessible reagents. Sulfonimidoyl fluorides bear both synthetic and pharmaceutical relevance as they enable direct access to other highly desirable sulfur(VI) motifs. This work serves as an advancement over comparable literature protocols as no unstable intermediates need be isolated, and the reaction is conducted in a single reaction vessel.

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