The Wittig reaction has constantly evolved during the last half-century and is one of the most strategic, reliable, widely-applicable carbon-carbon olefin bond forming processes available in organic synthesis. The reaction allows for olefination with complete positional selectivity, relatively high chemoselectivity and may be conducted in many cases with predictable stereocontrol. Triphenylphosphoranylides are ubiquitously employed and despite the myriad benefits these reagents bestow there are known disadvantages to their use—most prominently related to issues surrounding stereoselectivity and phosphine oxide removal which is notoriously problematic. Trialkylphosphoranylides, by contrast, undergo olefination in the presence of carbonyls with high (E)-stereoselectivity and the corresponding short chain trialkylphosphine oxides are water soluble. Previous work in our group has shown that semi-stabilised ylids of this type readily undergo olefination with a broad range of aldehydes under mild aqueous conditions. This aqueous Wittig reaction was then extended to the synthesis of substituted styrenes using aqueous formalin. In the search for ever milder conditions for the Wittig reaction we were also able to develop an organocatalytic Wittig reaction which was amenable to a bioorthogonal process. Thus, we were able to perform the first Wittig reaction in vivo by feeding the two reactants to Castylegia sepium. Alkenals (colloquially enals) are strategic intermediates in organic synthesis; their importance is growing each year due to the expanding breadth of iminium and vinylogous enamine organocatalysis. Unfortunately their preparation remains problematic requiring labour and reagent intensive multi-step sequences. A new pincolacetal-phosphonium salt (DualPhos) for the stereoselective two-carbon homologation of aldehydes has been developed which allows for the one-pot homologation of aldehydes to enals under aqueous and/or anhydrous conditions; its application to the total synthesis and stereochemical reassignment of phomolides G & H is discussed. / Thesis / Doctor of Philosophy (PhD)

No / The reactions of ionised pyridazine, aminopyrazine and aminopyridine and the corresponding ¿-distonic ions are examined by a combination of tandem mass spectrometric techniques, including analysis of metastable ion (MI), collision induced dissociation and neutralisation¿reionisation mass spectra (NRMS). Further insight into the relative stability and energy barriers towards tautomerism of each ionised heterocycle with its ¿-distonic isomer is obtained by computational methods. In all these systems, both the conventional radical-cation and the ¿-distonic tautomer are stable species which exist in discrete energy wells, with a significant barrier towards their interconversion. Although each ¿-distonic ion is sufficiently stable to survive neutralisation¿reionisation, the conventional ionised heterocycle is more stable in each case. The possibility of investigating proton-transport catalysis in the tautomerism of these ionic systems is discussed.