Taber, Sikkander, and Storck. JOC, 2007, ASAP. DOI: 10.1021/jo070257g.
A short synthesis and therefore a short post on the synthesis of this secondary metabolite from Laurencia cartilaginea. The family, bromochamigrenes, show selective, potent cytotoxicity in the NCI 60 cell antitumor, and are thus quite deserving of Douglass Taber’s work (who gave a nice lecture here on Tuesday). The key to the synthesis is the carbene insertion, but let’s look at the retro first:
As you can see, the exciting chemistry is happening at a damn congested neo-pentyl centre, so getting anything to happen is quite impressive. The forward shows that they managed this quite efficiently, producing the carbene via deprotonation/loss of bromide. This then inserts into the only available C-H bond (with a small amount of rearrangement product), generating the spirocycle in good yield.
Now, what I found really smart in this work was a “rearrangement” to the 6,6 spirocycle via ozonolysis of the olefin, followed by aldol to give the enone. Nice! I also like the use of hydrobenzoin to protect the ketone and allow resolution… not novel, but nice.