Nucleophilic catalysis of compounds in the ester oxidation state

Nucleophilic catalysis, and more specifically N-heterocyclic carbene catalysis is a powerful tool that can transform carbonyl containing starting materials to more complex products. The type of transformation that occurs depends on the nature of the intermediate that can be accessed which in turn is controlled by the nature of starting material, reaction conditions and catalyst. This thesis describes studies into exploring completely new intermediates in nucleophilic catalysis or exploiting established intermediates in new ways. The first chapter provides an overview of the reactivity patterns that can be seen in this field of catalysis, with transformations categorised by the key reactive intermediate. The acyl azolium, α,β- unsaturated acyl azolium, acyl azolium enolate, β-azolium enolate and hemiacetal azolium are all discussed. Chapter two describes studies towards the use of the novel α,β,γ,δ-unsaturated acyl azolium intermediate in reaction discovery, in this context in an all carbon formal (4 + 2) cycloaddition reaction. The development of this reaction is discussed and limitations in this methodology described and addressed. Chapter three describes the use of enol esters in an attempt to access similar intermediates. Through the use of harsher reaction conditions, novel bicyclo[2.2.2]octane materials were synthesised. The generality of the reaction was explored and mechanistic studies indicated that the reaction proceeded via a hemiacetal azolium intermediate, through at [1,5] shift mechanism to access an unstable unconjugated intermediate before thermal (4 + 2) cycloaddition. The reactivity of the products was further investigated and a brief study into an enantioselective variant of the reaction was also undertaken. Chapter four describes the investigation into utilizing NHCs as nucleophilic catalysts in intramolecular Diels-Alder (IMDA) reactions where the diene and dienophile are tethered by an ester. This synthetically challenging transformation arises due to the conformational resting state of the molecule and studies on using nucleophilic catalysis to address this are described in this chapter. Chapter five describes the application of nucleophilic catalysis in developing novel autocatalysts. This study introduces the possibility of exploiting nucleophilic catalysis to activate acyl and alkyl halide starting materials to nucleophilic attack by azido alcohols. Intramolecular 1,3-dipolar cycloaddition completes the catalytic cycle and produces another molecule of catalyst which is free to re-enter the catalytic cycle