Pagenkopf and Wang. Org. Lett., 2007, ASAP. DOI: 10.1021/ol701797e.
Just a quick Org. Lett. to get back in the saddle, so to speak. The target is certainly appealing; quite an interesting array of functionality there. It does have some biological activity, as a Na/K ATPase inhibitor, but isn’t particularly potent. The chemistry gets interesting with a desymmeterisation of a diol using an orthoester to provide the acetate. Then they form the first THF using a tasty Mukaiyama cobalt-catalyzed aerobic oxidative cyclisation, a method popular with the group. They state that the hydroperoxide is there to oxidise the cobalt up to Co(III), but I’m pretty sure that the atmospheric oxygen will do that alone…
Either way, a smart result. They repeat this technique shortly, after a bit of protecting group shuffling, generating the fused bis-THF required. The diene is appended by doing an oxidation followed by a pair of Wittig olefinations. On the other end of the molecule, an oxidation and alkylation provided the propargyl alcohol (interestingly using a titanium acetylide, used by Overman in similar work…). Treatment of this with LiCuBr2 gave the allene, with a strong bias towards the desired diastereoisomer (which, in the event, wasn’t the natural product). Nice chemistry!