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Totally Synthetic by Paul H. Docherty, 24 July 2007

Total Synthesis of Platensimycin


P. Li, J. N. Payette, H. Yamamoto, J. Am. Chem. Soc. 2007, 9534-9535.

DOI: 10.1021/ja073547n

This total synthesis of platensimycin by Yamamoto is quite elegant, and contains some amazing transformations. Their work differs from previous approaches by not forming the ether by alcohol addition to an alkene, but via a Robinson annulation.

On with the synthesis… Their work starts with an asymmetric Diels-Alder reaction on methyl cyclopentadiene and methyl acrylate using their BLA (Brønsted acid assisted chiral Lewis acid) catalyst. They then deprotonated the ester, and did a nitrosoaldol reaction to give the N-nitroso species. This was then decarboxylated to leave the desired ketone. Nice!

The next few steps to the Robinson precursor are nicely planned, and are executed with rather decent results, other than an unfortunately unselective cyanide addition to a lactol. I’m surprised at the lack of selectivity here, and also the choice of reagent: diethyl aluminium cyanide can’t have been at the front of the fridge! However, they explain that this was a Lewis acid mediated addition, which makes some sense to me.

A few more steps and they were ready to cyclise, using stoichiometric L-proline to control the addition to the Si face of the enone. This reinforced the substrate induce bias to achieve a 5:1 d.r., better than the 3:1 achieved using the unmatched D-proline case. The sodium hydroxide that follows then dehydrated to give the desired intermediate.

This paper was a good read, and an excellent synthetic plan.