Combining experiment and DFT to study new reactions

This thesis describes the use of density functional theory (DFT) to better understand chemical methods developed within the Unsworth and Lynam groups. Chapter 1 provides a summary of the theory underpinning computational chemistry and reviews the use of DFT to study gold(I)-catalysed reactions. In Chapter 2, an established method for the rearrangement of spirocyclic indolenines into quinolines under acidic conditions with heating is described. The rearrangement was further explored using basic conditions, where it was found that mild conditions can be used. The mechanism was studied using DFT to compare both conditions, where it was proposed that keto-enol tautomerism under acidic conditions is rate-limiting. In Chapter 3, the gold(I)-catalysed formation of 3-vinyl indole species was achieved using ynones. DFT was used to study the mechanisms of indole vinylation and bisindole formation, where it was found that ynones hinder the further addition of indole to the products. The speciation of the gold(I) complexes was studied using DFT and NMR spectroscopy, where a substituent dependence of the ynone was identified, and a gold(I)-pyrylium complex was characterised. In Chapter 4, DFT calculations that can be used to predict the viability of successive ring expansion (SuRE) reactions are described. DFT methodologies were benchmarked which demonstrated that the B3LYP/6-31G* level of theory can be recommended as the optimum method for modelling SuRE reactions. This method was then used to aid in the development of further SuRE reactions. In Chapter 5, a method for the acylation of lactams is described, via the intramolecular acyl migration of a nearby thioester moiety. DFT calculations aided in the development of the reaction, where it was predicted that the acyl-migrated intermediate would need to be trapped. The approach was validated with the use of ynones to trap the intermediate, and a successful SuRE reaction using this method, is described within.