Development of cross-coupling routes to macrocyclic polyenes: the first total synthesis of phacelocarpus 2-pyrone A

This thesis describes the development of a synthetic approach to an unusual pyrone-containing macrocyclic natural product isolated from the marine alga Phacelocarpus labillardieri. This comprises the synthesis of a simplified model system followed by the completion of the first total synthesis of the natural product and its suggested stereochemical reassignment, as well as studies on related palladium catalysis methodology. An overview of macrocyclic 2-pyrone natural products is given initially, along with a discussion of 2-pyrone reactivity and general macrocyclisation strategies in natural product synthesis (Chapter 1). The synthetic route was originally developed for the synthesis of the aromatic analogue, and various attempts and strategies towards this compound are described, culminating in its completion (Chapter 2). An account of the application of this strategy to the successful synthesis of the natural product is then given, the accomplishment of which allows a reassignment of the stereochemistry around the enol ether double bond from the previously assigned E to Z in the natural compound (Chapter 3). The remainder of the thesis focuses on two studies carried out on succinimide-based palladium complexes. The first concerns an investigation into the effect of air on the efficiency of Stille cross-coupling reactions catalysed by an established catalyst (Chapter 4), and the second an examination of two novel complexes including their synthesis, characterisation and catalytic activity (Chapter 5)