Development of second generation scaffolds for iminium ion catalysis

This thesis embraces two main sections that examine alternative architectures for the iminium ion catalysis of the Diels-Alder reaction - comprising acyclic and cyclic systems. Chapter 1 provides an overview of iminium ion and enamine catalysed processes. Focus is on the structural requirements of catalysts for effective and efficient transformations. Chapter 2 highlights work carried out previously within the group and provides a more in depth review of the Diels-Alder reaction, the protocol adopted for comparing catalyst activity and methods by which results were analysed. Chapter 3 describes the design and synthesis of a series of five membered cyclic catalysts based on the pyrazolidine subunit. These systems incorporated aspects of acyclic catalysts developed previously within the group to decrease reaction times and catalyst loadings. Reaction conditions were optimised with regards to solvent and acid co-catalyst. SAR studies of the cyclic and acyclic architectures lead to the expansion of the acyclic series within Chapter 4. This resulted in the most active acyclic catalyst to date with a conversion of 98% after of six hours within the iminium ion catalysed Diels-Alder reaction. Chapter 5 shows a combination of SAR studies and computer modelling that led to the design and synthesis of a series of six-membered cyclic analogues containing an a-heteroatom. These systems catalysed the Diels-Alder reaction more efficiently producing a conversion of 89% after three hows and 99% after six and would provide an effective architecture for the development of a chiral catalyst A trend was discovered relating the electronic environment of a p-carbonyl incorporated into the catalyst structure and its associated activity with supporting evidence from an associated computational project Finally, Chapter 6 describes preliminary studies into the three proposed component steps of the iminium ion catalysed Diels-Alder reaction. 1H NMR and UV spectroscopy was (and continues to be) used to examine these steps to gam valuable information iiyrilUig the mechanism of the catalytic cycle