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Totally Synthetic by Paul H. Docherty, 14 April 2007

Total Synthesis of Platensimycin


K. C. Nicolaou, Y. Tang, J. Wang, Chem. Commun. 2007, 1922-1923.

DOI: 10.1039/B704589A

This total synthesis of platensimycin (another will follow) by Nicolaou is a formal synthesis, actually going to the same intermediate that Snider did in the last post. Looking at these two papers, alarm bells started ringing, as the retrosyntheses look quite similar:

This strategy seems quite popular! The interesting bit, I guess, is then the synthesis of that decalin, which thankfully uses an entirely different approach. They got to a quite complex intermediate very quickly by just doing a pair of enolate alkylations. With a few functional group transformations, they were then set for the most interesting reaction in this paper:

With this dione complete, reduction and closure of the conformationally closer hydroxyl onto the alkene generated the THF, leaving the other hydroxyl ready for triflation and elimination. All that was remaining was to perform an allylic oxidation - but this was a bit more traumatic than one might expect. Efforts with chromium trioxide were unsatisfactory, as the allyl cation produced could oxidise on either end. They then moved to selenium dioxide, which either reacted too much, to produce the dienone, or the allylic alcohol. However, a little manganese dioxide allowed the latter to be converted to the desired enone in good overall yield.

Now that’s a nice Stetter reaction! They state that they tried a number of carbene-based catalysts, but found that the triazole catalyst shown was optimal. I noticed that the catalyst featured a perfluoro phenyl group - which maybe means they could use Curran’s fluorous phase chromatography to separate it with ease. Anyway, it’s certainly a sweet method to put that system together.

I’ll describe the asymmetric synthesis shortly