Synthesis of heterocycles using metal and base catalysis

Abstract

Brevetoxin B was isolated from the organism Gymnodium breve, its structure was determined as containing 11 trans-fused oxygen heterocycles, of which eight are fused pyrans, two are used polyoxepanes and one alone was a trans-fused eight membered ring.It has become a formidable challenge for synthetic organic chemists. We have made progress toward the formation of the fused pyran segment, initially investigating the formations of pyran rings via the metal catalysed cyclisations of allene diols. This however posed a great challenge, as the allene proved unwilling to undergo the desired 6- exo-cyclisation, instead favoring the undesired 5-e«afo-cyclisation, to form an undesired furan. Subsequently we have revised our synthetic route to investigate the cyclisation of a range of Michael accepters by Michael addition of a pendant oxygen nucleophile. As a result of these studies we have obtained a route to a functionalised pyran by tandem deprotection and cyclisation under basic conditions. We are currently in the progress of demonstrating the iterative nature of this synthetic route and the mild cyclisation conditions.