| dc.description.abstract | The discovery of a class natural products with anti-cancer properties, the enediynes, has
stimulated interest in their research. Due to their cytotoxicity, these compounds are not feasible
for use in cancer treatment, however, synthetic work has centered around improved stability,
reduced toxicity and elucidation of the mechanism of the Bergman cyclization reaction.
Protocols utilizing palladium-catalysed cross coupling reactions have been used extensively in
the synthesis of enediyne analogues. Little work to date has investigated the effect of
heteroatoms on the success of coupling reactions, thermal Bergman cyclizations and
photochemically induced cyclizations. In this thesis, a synthetic study involving the coupling
reactions o f nitrogenous aromatic halides, halotriflates and a series of alkynes will be presented.
Several enediyne analogues were synthesized in moderate to high yields, isolated and
characterized. In general, it was observed that nitrogen heteroatoms increase the reactivity
toward Sonogashira coupling reactions. In order to examine the effect o f resonance and
inductive effects on the reactivity under Sonogashira conditions, a series o f competitive reactions
between m- or p-substituted aryl iodides and iodobenzene were performed. In general, electron
withdrawing substituents in the m- or p-positions increased the reactivity, while electron donating substituents decreased it. It was observed that resonance effects have a larger effect on
reactivity than inductive effects. Thermal and photochemical cyclization studies were performed
for the nitrogenous aromatic enediynes synthesized. None o f the enediynes were observed to
cyclize thermally, while only the TMS- and phenyl-substituted enediynes were observed to
photochemically cyclize. | |
