Corey, Mushti and Kim. JACS, 2006, ASAP. DOI: 10.1021/ja066336b.
Another top synthesis of an interesting polycyclic target, this one with a complex nine-four-six ring system at its core. The structure was determined almost twenty years ago, but the synthesis has apparently slipped through the cracks, along with the absolute stereochemistry. No details on the activity of the target were given in the paper, but I’ve not read the isolation reference yet, so perhaps it does something… however, the synthesis is what we’re interested in
After eight steps, the workers achieved a complex cyclisation precursor, full of synthetic handles. Saponification of the ester however, kicks things off, and with salt formation and treatment with tosyl chloride in base, a ketene intermediate is formed. This then performed an intramolecular [2+2], generating the cyclobutane and the useful remaining carbonyl group. This transformation has been somewhat of a Corey favourite, and several references in the paper point to other work containing this style of reaction.
With the carbonyl handle, functionalisation of the cyclobutane was easy, allowing ethylation, and at this point they did a resolution via chiral HPLC. Further functionalisation led them to a Î²-keto sulfone, with which they did an interesting Pd-catalyzed [2,3]-sigmatropic rearrangement:
Again, this interesting cyclisation left them with a useful synthetic handle, as well as the desired ring (in this case a difficult to form trans-nonene); however, the sulfone was removed via Al-Hg amalgam. Completion of the synthesis was then in sight, via eventual clevage of the five-member ring (using the periodate on silica reagent I mentioned in a previous comment), and formation of the six-rings by stirring in silica:
I know the last transformation is well precendented stuff, but it’s stuff I like .