Applications of Imino-Diels–Alder Reactions in Synthesis
Author(s)
Chahal, Jasprit Kaur
Type
Thesis
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.
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.
Date Issued
2012
Date Awarded
2012-03
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Craig, Donald
Sponsor
EPSRC; GlaxoSmithKline
Publisher Department
Chemistry
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)