Doctor of Philosophy
School of Chemistry and Molecular Bioscience
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.
Thadkapally, Srinivas, Transition Metal-Catalyzed [4+2]-Cycloaromatization Reactions of Unconjugated Enediynes, Doctor of Philosophy thesis, School of Chemistry and Molecular Bioscience, University of Wollongong, 2021. https://ro.uow.edu.au/theses1/1164
FoR codes (2008)
0305 ORGANIC CHEMISTRY
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.