Year

2021

Degree Name

Doctor of Philosophy

Department

School of Chemistry and Molecular Bioscience

Abstract

The project was designed to investigate a new class of unconjugated enediynes under transition metal-catalysis conditions, as this was expected to provide direct access to aromatic bicyclic products. Firstly, construction of the stereodefined (Z)-enynols was achieved using a multistep procedure, starting from commercially available methyl propiolate. As part of this sequence, (Z)-3-iodoacrylate was synthesized via a hydrohalogenation reaction by treating methyl propiolate with NaI in acetic acid at 70 °C. This was then converted via a Sonogashira cross-coupling and reduction to a (Z)-enynol. The novel unconjugated enediyne substrates were synthesized finally prepare from this (Z)-enynol, which upon treatment with NaH and propargyl bromide successfully furnished the simple unconjugated O-tethered (Z)-enediynes.

Initially, this enediyne was reacted under Au(I)-catalyzed conditions to provide the cycloaromatized product. Interestingly, at room temperature, this reaction underwent a single cleavage mechanism providing the 5-membered intermediate. This intermediate undergoes tandem cyclization via a second Au(I)-catalyst activation under thermal conditions to the cycloaromatized isobenzofuran product. However, the substituted enediynes failed to undergo cycloaromatization and the CH3-substituted enediyne provided an unstable 5-membered intermediate and trace amounts of a 6-membered ring product. These unsuccessful cyclization reactions of substituted enediynes could be a result of the steric hindrance to formation of the fused cyclopropane Au-carbene intermediate leading to single cleavage rearrangement.

FoR codes (2008)

0305 ORGANIC CHEMISTRY

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.