The chemistry of 1,2-dioxines.

l,2-Dioxines are an important class of compounds that are useful in organic synthesis for the incorporation of 1,4-oxygen functionality. 1,2-Dioxines contain a weak peroxide bond that may be readily reduced and which may also undergo transition metal mediated homolysis yielding reactive cis-γ-hydroxyenone intermediates. These cis-γ-hydroxyenone intermediates undergo cyclopropanation when allowed to react with stabilised phosphorus ylides. The synthesis of some l,2-dioxines is presented. This is followed by an investigation into the cobalt catalysed rearrangement of unsymmetrical 1,2-dioxines to cis-γ-hydroxyenones. The unstable product cis-γ-hydroxyenones were characterised using 2D NMR and also derivitised with a stabilised phosphorus ylide. Cyclopropanes and 2E,4Z-dienoates were prepared in good yield and it was found that the relative ratios of the derivitives could be used to examine the ring-openings. It was found that the selectivity for the cobalt catalysed rearrangement was controlled by the steric bulk of the substituents on the 1,2-dioxines. The cis-γ-hydroxyenones generated from 1,2-dioxines also undergo cyclopropanation when allowed to react with sterically encumbered stabilised phosphorus ylides. The products that derive from the reaction contain a different substitution pattern than when non bulky ylides are used. The origins for the selectivity are discussed. It was discovered that lithium bromide also directs the selectivity of the rearrangement towards these new isomers. The cyclopropanes generated above were found to undergo a novel C₃-C₅ ring expansion reaction when allowed to react with strong hindered amine bases such as lithium hexamethyldisiazide. The mechanism for the reaction was probed and is discussed. The mechanism was proposed to be a sequential enolisation / ring-opening / aldol process. Further modifications of the cyclopentenes are discussed. A novel dimerisation of cis-γ-hydroxyenones catalysed by lithium hydroxide was found giving rise to highly substituted tetrahydrofurans. Both l,2-dioxines and trans-γ-hydroxyenones could be used as starting materials for the dimerisation. The reaction mechanism was proposed to be an oxy-Michael / Michael cyclisation reaction giving the observed tetrahydrofurans. The epoxidation of 1,2-dioxrnes was also investigated. The epoxidation went in excellent yield. The epoxy-1.2-diorine products could be ring-opened using both Co(II) catalysis and amine bases via a Kornblum / Delamare reaction. The epoxy-1,2-dioxines were also found to possess both antifungal and antimalarial activity.

Author dc:creator

• Greatrex, Ben William

Advisor dc:contributor.advisor

• Taylor, Dennis Kenwyn

• cyclopropanes; lithium; hydroxide; dioxines

Handle dc:identifier.uri

http://hdl.handle.net/2440/62554

OAI identifier oai:identifier

oai:digital.library.adelaide.edu.au:2440/62554