The adoption of unusual functional groups into medicinal and agrochemical research programmes provides enhanced coverage of both chemical and intellectual property space. In this regard, sulfoximines and sulfonimidamides, the mono-aza analogues of sulfones and sulfonamides respectively are receiving considerable attention as bioisosteres in drug design. However, restrictive synthetic methods have, in part, limited the utility of these motifs in the life sciences. In this thesis, the development of synthetic methodology towards accessing these nitrogen containing sulfur(VI) functionalities is described.
Initially, a procedure for the gram scale preparation of enantioenriched sulfoximines from sulfoxides is described. This methodology builds upon previous NH transfer work, with a focus on how this can be applied in a safe and robust manner on larger scales. Next, thiols are explored as substrates under NH and O transfer conditions and are subsequently shown to be suitable precursors to sulfonimidates or primary sulfonamides depending on the reaction conditions.
Further extension of this NH and O transfer methodology to sulfenamides allows access to sulfonimidamides in just two straightforward steps from commercially available starting materials. This methodology is applicable to late stage functionalisation reactions as well as in the preparation of an aza-analogue of a marketed drug. Novel 6-sulfanenitrile species are identified as intermediates in the NH and O transfer, shedding further light onto the mechanism of these reactions.
Finally, sulfinamide salts are isolated for the first time and are shown to be effective precursors to sulfonimidoyl fluorides, giving rise to the first facile route toward enantioenriched sulfonimidamides through a sulfur fluoride exchange (SuFEx) reaction.
A summary of specific conclusions and future work can be found in the penultimate section. Experimental details and data for all compounds synthesised during this research can be found in the final section.