Dimethyl Gloiosiphone A
Takahashi, Doi, Iijima and Takasaki. JOC, 2007, ASAP. DOI: 10.1021/jo062546v.
At first, I loved the look of this synthesis; take one really simple acyclic precursor, dump in a little of everyone’s (or at least my) favourite palladium catalyst, and hey-presto – instant 5,5-spiro fused ring system. 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 (okay, one is an allyl acetate…). 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 sweet. The only slight flaw was a lack of diastereomeric control at the OMPM centre, but that was soon to be oxidised, so was irrelevent. 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 pi-allylpalladium intermediate, followed by Heck cyclisation.