The chemoenzymatic synthesis of the lycorine framework and the synthesis of C-3-mono-alkylated oxindoles via the palladium-catalysed Ullmann cross-coupling reaction

Abstract

Chapter One of this Thesis briefly describes the history and production of cis-1,2-dihydrocatechol chiral starting materials and summarises their synthetic attributes as well as providing several examples of their use in natural product synthesis. Chapter Two begins with a succinct review of the structural characteristics and biological properties of the Amaryllidaceae alkaloid ({uF02D})-lycorine and describes several established synthetic approaches to compounds of this type. Thereafter, experimentally-based research leading to the development of a rapid and enantioselective synthesis of the lycorine framework, starting from the cis-1,2-dihydrocatechol and culminating in the syntheses of two lycorine derivatives is described. Additionally, the true structure of the Amaryllidaceae alkaloid nobilisitine A is disclosed. Chapter Three provides a short review of the classic Ullmann bi-aryl synthesis and introduces the Pd[0]-catalysed variant. The synthesis of indoles and quinolones via a Pd[0]-catalysed Ullmann cross-coupling/reductive cyclisation approach is then described. Thereafter, research leading to the efficient synthesis of C-3 monoalkylated oxindoles by such means is presented. Chapter Three also presents the results of methodological studies directed towards improving the efficiency of the Pd[0]-catalysed Ullmann cross-coupling reaction by using highly activated copper powders. This theme is developed further in Chapter Four.