This thesis focuses on the use of unsaturated aldols as useful substrates in natural product synthesis. Two methodologies have been investigated for the asymmetric synthesis of highly substituted lactones containing multiple contiguous stereocentres from unsaturated aldol precursors. These lactones have potential application as building blocks for natural product synthesis. Firstly, synthetic applications of the retro aldol reaction are reviewed.The second chapter describes a novel methodology for the asymmetric synthesis of highly substituted δ-lactones from syn-aldol cyclopropanes iii. Mercury mediated cyclopropane ringopening of the methyl ester cyclopropanes iv followed by concomitant cyclisation produced organomercurial δ-lactones v, which subsequently undergo reductive demercuration in basic sodium borohydride to afford the highly substituted δ-lactones vi in good yield and excellent diastereoselectivity. The scope of this method was investigated with variation of the R1 and R2 groups. The synthetic utility of this process was also demonstrated with the synthesis of a series of (+)-Prelactone natural products.The third chapter decribes a method of preparing hydroxy-γ-butyrolactones (viii-x) containing multiple contiguous stereocentres in high yield with good diastereoselectivity. Upjohn dihydroxylation conditions using catalytic osmium tetroxide were employed to β-alkenyl-β- hydroxy-N-acyloxazolidin-2-ones vii with different alkene substitution patterns. This resulted in the formation of triols that underwent spontaneous intramolecular 5-exo-trig cyclisation reactions to afford hydroxy-γ-butyrolactones viii, ix or x depending on the substitution pattern of the alkene precursor.
|Date of Award||31 Dec 2013|
|Supervisor||Steven Bull (Supervisor)|