|Abstract: ||The aim of the project is to synthesise (–)-morphine utilising aziridine and metathesis
chemistry. The thesis is divided into three chapters.
Chapter 1 provides brief reviews on the subjects of total synthesis of morphine; ringrearrangement
metathesis (RRM) and regioselective ring-opening of aziridines.
Chapter 2 focuses on the research findings in the past three years. Two routes, A and B,
were investigated in attempts to synthesise morphine (Scheme 1). In route A, sulfonyl
cyclopentene II was prepared from ring-closing metathesis of a diene precursor, which
was synthesised from lithiated cinnamylsulfone and butadiene monoxide. Subsequently,
RRM reactions of several α-SO2Ph allyl derivatives of II were investigated and some
interesting results were obtained. The synthesis of 2,3-trans vinylaziridine III was
achieved in seven steps beginning with a Grignard reaction of (4-
methoxyphenyl)magnesium bromide with butadiene monoxide. Subsequently, some
highly regioselective ring-opening reactions of III with sulfur-stabilised anionic
nucleophiles were achieved. However, in an attempt to synthesise compound I from II
and III, no reaction was observed. This led to the investigation of route B, in which five
methods for the synthesis of compound IV were investigated. The practical approach
deployed a novel Al-mediated substitution of the 4-tosyl group of the tosyl
tetrahydropyridine counterpart of IV, prepared from V and III, with a phenylthio group.
Chapter 3 provides the experimental details and characterisation data.|