Canesi, Sabot and Berard. Org. Lett., 2008, 10(20), 4629-4632. DOI: 10.1021/ol801921d.
I nearly missed this paper, published online at the beginning of last month, but it’s an incredibly neat solution for the synthesis of some funky little natural products.Â The parent molecule, panacene, has some fairly unique biological properties, as it is a shark-antifeedant.Â In otherwords, it puts sharks of their food, and makes the sea-hare in which it is produced that little bit less attractive to the peckish big-fish.Â Okay, so it doesn’t cure cancer, but the next time you’re swimming in the Med…
I suspect (though I’ve no justification) that this paper was a get-the-methodology-then-find-the-target type of study, but it’s certainly methodology that seems to work rather well.Â The key motif is a umpolung addition of furan to phenolic-type systems (or more largely electron-rich aromatics), using iodobenzene diacetate to generate a cationic intermediate that allows attack of furan.Â Sort-of reminiscent of Friedel-Crafts chemistry.Â The oxonium ion produced is then rearranged by attack of the ketone to provide a 6,5,5-fused system in a reasonable yield.Â There is a selectivity issue as to which position ortho to the phenolic hydroxyl is fused, but this was overcome by using a TMS blocking group.
With the desired system in place, it was time to add the desired allenic sidechain.Â Two different approaches were used to impart the different sidechains, with the unhalogenated desbromopanacene made most succinctly in only two steps from a common (desilylated) intermediate.Â Firstly, the DHP DHF was oxidised hydrated to the hemiacetal using an oxo-mercuration (rather them than me…) / borohydride process.Â Treatment of this with a propynylsilane under Lewis-acidic conditions allowed a Sakurai reaction, neatly completing the target in good yield.
For the parent molecule, panacene, the brominated allene moiety meant that a more complex route was required.Â Using the same hemiacetal shown above, they did a Wittig olefination to give a enyne.Â Again, a spot of mercuric acetate was used, but this time the product was a mercuric allene.Â To give the target, they did an in-situ protiodemercuration using ethandithiol, which was impressively stereoselective.Â Nice stuff!