Baran, Maimone and Richter. Nature, 2007, 446, 404-408. DOI: 10.1038/nature05569.
If you read this blog, and you haven’t hassled me about a post on this paper, you’re actually in the minority. It’s from what appears to be a bit of a special on chemistry – or at least I’m not used to seeing quite this much in Nature. In the commentary, we’ve got a highlight by John Porco on this paper, a piece on C-H activation, and a review by F. Dean Toste on relativistic effects in gold catalysis. And as pointed out in a previous comment, I’m in it too…:)
Anyway on with the synthesis:
Nice. They actually investigated the coupling with plain indole, but even though they got a good yield, the subsequent 6-exo-trig cyclisation went best with the bromide in-place. Interestingly, radical cyclisation conditions went via a 7-endo-trig route, which I wouldn’t have thought to be so facile.
I’ve missed out the next few steps, primarily because they are a little less novel, but also because if I transcribed them, I’ve have done the whole synthesis… Anyway, with Hapuindole U done, all that was required was to install the tert-prenyl unit onto C2 of the indole – but direct methods weren’t compatible with that funky isonitrile. However, following a Danishefsky protocol, they formed the pentacyclic chloroimidate by addition of prenyl-9-BBN.
Now things get rather tasty – a Norrish-type 1 (I think) cleavage of the chloroimidate, followed by the usual hydrogen abstraction allowed deborylation and reduction back to the indole with the prenyl group in place – top banana!
Sweet synthesis, over in six steps! I can’t believe how good that last sequence is… Anyway, we’ll look at welwitindolinone A and fischerindole I in a couple of days…