Applications of Imino-Diels–Alder Reactions in Synthesis

Abstract

The aim of the project was to synthesise (−)-morphine utilising a tethered intramolecular imino-Diels–Alder reaction. This thesis begins by providing brief reviews on the subjects of total synthesis of morphine and asymmetric imino-Diels–Alder reaction. The major section focuses on the research findings in the past four years. Starting with investigations in the development of a novel stereoselective imino-Diels–Alder reaction of methyl propargyl ether derived (1E,3Z)-1-silyloxy-3-(phenylthio)-1,3- dienes with trans-2-phenylcyclohexyl glyoxylate derived N-tosylimine. Following with the progress made so far to synthesise triene II; this was envisaged to be prepared from the enantiomerically pure alcohol III and allylic halide IV. The alcohol III was prepared in a five-step sequence from p-anisaldehyde. However, the synthesis of the allylic halide IV from D-lyxose was more challenging and problematic. Initial efforts for its synthesis via a route incorporating the Ohira–Bestmann reaction caused an unwanted epimerisation. Further efforts, through an eleven-step sequence including Wittig dibromomethylenation and intramolecular ene–yne metathesis gave V or VI. However, the reductive eliminations to give the alcohol precursor to IV were unsuccessful. [Molecular structure diagrams appear here. To view, please open pdf attachment]. Experimental details and characterisation data are provided at the end of the thesis.