Synthesis of novel aza-sulfur(VI) compounds

Thesis

S(VI) based moieties exhibit promising pharmacological properties, and are present in over 150 FDA approved drugs currently available on the market. In this thesis, a variety of vinyl sulfonimidamides were synthesised and evaluated for their potential as bioisosteres of acrylamides. Furthermore, a novel methodology for the synthesis of rarely reported iminosulfamides was developed, employing a Lewis-acid mediated SuFEx amination system. The method enabled access to a broad variety of iminosulfamide derivatives with different amidic components.

Chapter 1 is a review introducing S(VI) functionalities, focusing on current synthetic strategies used for accessing sulfonamides, sulfonimidamides, sulfamides and iminosulfamides. The properties and application of these compounds are also described.

Chapter 2 focuses on the synthesis of NH vinyl sulfonimidamides, through a single-step from an aryl ONSO reagent, a vinyl organometallic, and an appropriate amine. These vinyl sulfonimidamides have shown good reactivity towards cysteine and lysine derived nucleophiles, and the electrophilicity of these reagents can be modulated by choice of the imidic N-substituents and alkene substituents to achieve reactivity either above or below the corresponding acrylamide.

Chapter 3 describes a general and practical approach for synthesising a variety of sulfuramidimidoyl fluorides, through a key elimination/fluorination process using sulfonimidamide substrates. With the installation of electron withdrawing pivaloyl group, the reactivity of the S(VI) fluoride was enhanced, and a mild SuFEx amination reaction allowed the access to a wide variety of iminosulfamides, which were previously considered synthetically challenging.

Chapter 4 summarize the research and discusses potential areas for future work.

Chapter 5 provides experimental procedures and data for this research.

Authors: Wong, YT

• DOI: 10.5287/ora-7jwk8ddnj
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English