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).