Rhodium carbenoid mediated cyclisations. Part 4. Synthetic approaches to oxepanes related to zoapatanol

Abstract

Synthetic approaches to the oxepane diterpene zoapatanol are described, in which the key step is the formation of the 7-membered cyclic ether by a rhodium carbenoid cyclisation. The model oxepane (15) was synthesised from (E)-geraniol by selective epoxidation of the allylic alcohol, followed by conversion into the corresponding epoxy iodide (9). Reaction of the iodide with the anion of ethyl acetate gave, after opening of the epoxide, diazo-transfer and acetylation, the substrate (14) for cyclisation. Treatment of (14) with rhodium(II) acetate resulted in cyclisation to the required oxepane (15) in good yield (Scheme 3). The approaches to the functionalised side chain of zoapatanol centred on the allylic alcohols (25), prepared by allylic oxidation of geraniol and functional group transformation. After asymmetric epoxidation, these substrates were converted into the diazo alcohols (30) using a similar sequence to above (Scheme 5). Finally, cyclisation using rhodium(II) acetate gave the unstable optically active oxepanes (31), which were characterised by conversion into the silyl enol ethers (32).