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Totally Synthetic by Paul H. Docherty, 14 May 2007

Total Synthesis of Dimethyl Gloiosiphone A


T. Doi, Y. Iijima, M. Takasaki, T. Takahashi, J. Org. Chem. 2007, 72, 3667-3671.

DOI: 10.1021/jo062546v

At first, I loved the look of this synthesis; take one really simple acyclic precursor, use well known palladium catalyst, and the 5,5-spiro fused ring system is synthesised. However, after that reaction, things go off-the-rails a little…

The substrate, as I said, was made very quickly, doing a double Tsuji-Trost allylic alkylation with the bis(phenylsulfonyl)methane on two allyl halides/acetates. They were then set to cyclise, using the same catalyst and ligand as in the past two reactions - however, they had to be careful not to get diallylation with only one electrophile.

No arguments - that is efficient. The only slight flaw was a lack of diastereomeric control at the OMPM centre, but that was soon to be oxidised, so was irrelevant. However, the process of getting to the target material was prolonged - fifteen further steps in total, and twelve to a known intermediate. Not exactly concise, but still a nice example of a domino intramolecular alkene insertion to a π-allylpalladium intermediate, followed by Heck cyclisation.