Use and applications of sulfur dioxide surrogates in the synthesis of sulfonyl derivatives

Thesis

This thesis presents the development of novel methodologies toward the synthesis of a range of sulfonyl derivative compounds. These processes employ easy-to-handle sulfur dioxide surrogate DABSO (vide infra) and exploit the ability of the sulfonyl functional group to react on both the sulfur atom and the oxygen atom to deliver compounds such as sulfoxides, sulfonate esters and sulfinate esters.

Chapter 1 is a literature review of the synthesis and applications of sulfonyl-containing compounds and the organic chemistry of sulfur dioxide. The discovery and established used of the various kind of sulfur dioxide surrogates with organometallic reagents, metalcatalysts, and metal-free conditions for the synthesis of sulfonyl-containing compounds is also described.

Chapter 2 describes the development of a one-pot process for the synthesis of unsymmetrical sulfoxides and sulfinamides using organometallic nucleophiles, DABSO, and trimethylsilyl chloride.1 Reacting sulfur dioxide with an organometallic reagent provides a metal-sulfinate intermediate. In situ conversion of the sulfinate to a sulfinate silyl ester, using TMS-Cl, generates an electrophilic species, which enables the addition of a second nucleophile (an organometallic reagent or a metal-amide complex) for the synthesis of the desired sulfoxide or sulfinamide products.

Chapter 3 details the synthesis of pentafluorophenyl sulfonate esters based on a novel copper-catalysed oxidative transformation of in situ generated aryl and heteroaryl sulfinates to the corresponding sulfonate esters. The sulfinate intermediates are synthesised from boronic acids and DABSO, under the action of a palladium catalyst. The use of aryl bromides as suitable substrates for the synthesis of sulfinate ester was also established.

Chapter 4 documents various catalysed processes employed to promote enantioselective ring-opening of epoxides with sulfinic acid as nucleophile. Firstly, the use of metal-salen complexes is reported and shows the formation of the corresponding b-hydroxy sulfonate ester products. Secondly, the unexpected reactivity of sulfinic acid with epoxides under the control of phosphoric acid provides a simple and attractive route to useful b-hydroxy sulfinate species.

Chapter 5 presents a summary of the research and the potential future work.

Chapter 6 provides experimental details and data.

Authors: Vedovato, V

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford