Totally Synthetic by Paul H. Docherty, 26 October 2008

Total Synthesis of Panacene

Canesi

C. Sabot, D. Bérard. S. Canesi, Org. Lett. 2008, 4629-4632.

DOI: 10.1021/ol801921d

Panacene has some fairly unique biological properties, as it is a shark antifeedant. In otherwords, it puts sharks of their food, and makes the sea hare in which it is produced less attractive to the peckish big fish.

The paper offers an incredibly neat solution for the total synthesis of Panacene. The key motif is an 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. The oxonium ion produced is then rearranged by attack of the ketone to provide a 6,5,5-fused system in a reasonable yield. 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. 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. Firstly, the DHF was hydrated to the hemiacetal using an oxo-mercuration / borohydride process. 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. Using the same hemiacetal shown above, they did a Wittig olefination to give an enyne. Again, mercuric acetate was used, but this time the product was a mercuric allene. To give the target, they performed an in situ protiodemercuration using ethandithiol, which was impressively stereoselective. A very interesting synthetic step!