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Totally Synthetic by Paul H. Docherty, 7 November 2006

Total Synthesis of Monocerin


J. H. Cassidy, C. N. Farthing, S. P. Marsden, A. Pedersen, M. Slater, G. Stemp, Org. Biomol. Chem. 2006, 4, 4118-4126.

DOI: 10.1039/B612256F

A really short but effective total synthesis of the anti-fungal and insecticidal natural product monocerin is in the current issue of OBC. Interestingly, the article points out that the target has been isolated from many sources, which at first surprised me, but on second thought, can’t really be that rare… The synthesis, as I said, is really short, and is based on some methodology the group has been pursuing for the last few years. They’ve shown in a couple of papers that they can quickly construct substituted THFs via condensation of cyclic allylsiloxanes with aldehydes. Although the seven-member ring starting material looks complex, they’re able to make it in good yield simply by RCM with an allylsiloxane and terminal olefin.

As shown, the Lewis acid mediated condensation goes in excellent yield, and with 9:1 dr. Although it would seem that the synthesis is nearly done, they had a little trouble progressing to the natural product. An excellent, and rather surprising 6-endo Heck, in 67% yield, gave them the 5,5,6 system with a terminal olefin, which was quickly converted to the ketone. Unfortunately, the Baeyer-Villiger to complete the skeleton gave the wrong regiochemistry - the isomeric lactone! However, an alternative strategy took them to the natural product in four steps, with an interesting selective demethylation with BBr3 to give the desired phenol.

A nice read, especially the discussion regarding that Heck coupling