Novel applications of catalytic aza-Wittig chemistry

This thesis details recent advances in the field of redox neutral organocatalytic aza-Wittig chemistry, contributing to ongoing research into the development of novel catalytic processes for the synthesis of heterocycles. Work described herein forms the next chapter in continuing research into the organocatalytic aza-Wittig reaction first published by the Marsden group in 2008. Three distinct applications of novel catalytic aza-Wittig chemistry are reported.
The first chapter reviews recent advances in the field of organocatalytic phosphorous reactions, covering both redox-mediated and redox-neutral methodologies. While there has been a recent spate of publications detailing a range of phosphine catalysed reactions the majority detail a redox mediated system whereby the phosphine oxide waste is reduced in situ to the active phosphine species which undergoes traditional reaction conditions, for example the Wittig, Staudinger and Appel reactions. Work by the Denton and Marsden group offers an alternative strategy employing a system which maintains a phosphorus(V) oxidation state.
The subsequent results and discussion sections comprises four areas. Firstly, the use of hydroxamic acids and hindered ureas as masked isocyanate starting materials was investigated. The Lossen rearrangement was found to be a valid alternative to the Curtius rearrangement for the in situ formation of isocyanates for the application of the catalytic aza-Wittig reaction. 1,1-Diisopropyl ureas were found to behave as masked isocyanates which produced the isocyanate on heating again proving to be suitable as starting materials for the catalytic intermolecular aza-Wittig. A range of phenanthridines were synthesised using the azide-free intramolecular aza-Wittig reaction, employing hydroxamic acids as starting materials.
For the first time, the redox-neutral aza-Wittig reaction was used for the synthesis of a benzodiazepine, a biologically active seven-membered ring system. Catalyst loadings of 5 mol% were successfully employed with no loss in yield.
Finally, the metathetical nature of the catalytic aza-Wittig reaction was explored in the context of aza-enyne metathesis, an analogous reaction to the well-known metal catalysed enyne metathesis reaction. This novel reaction pathway led to the synthesis of a trisubstituted quinoline from simple and commercially available starting materials and led to interesting mechanistic observations.
Relevant experimental procedures are reported in full alongside data for synthesised compounds. Bibliographic data is also presented at the back of the report.