Methodology studies on one and two carbon ring expansion on polyether polycyclic natural products

Medium sized cyclic ethers are found in many natural products, with the most notable example being the polyether polycyclic family of marine toxins. Due to their increased size loss of entropy, torsional strain and unfavourable transannular interactions, as well as other effects require different synthetic approaches than the smaller homologues. In this work, different pathways were explored for the efficient synthesis of the seven-, eight- and nine- membered rings of marine polyether polycyclic natural products, through the expansion of a common six-membered ether substrate. The effect of the Lewis acid promoted TMS-diazomethane ring expansion of cyclic ketones was investigated and was successfully applied for the efficient synthesis of the oxepane and oxocane ring systems. Furthemore, a [2+2] cycloaddition between a seven-membered cyclic silyl enol ether and ethyl propiolate was examined for the concise formation of nine-membered cyclic ethers from an easily accessible substrate.