Welwitindolinone & Fischerindole
Baran, Maimone and Richter. Nature, 2007, 446, 404-408. DOI: 10.1038/nature05569.
There’s actually not too much more to add to this synthesis of three further related natural products – using chemistry familiar from the previous synthesis, they were able to complete 11-epi-fischerindole G in only six steps from carvone oxide. With this target already complete, a simple oxidation with DDQ returned fischerindole I in one step and in a great yield.
However, using xenon difluoride for fluorohydroxylation of the indole was certainly less simple; the disconnection to electrophile addition, addition of water, rearrangement and then elimination of the “electrophile” was inspired. The molecule then underwent a [1,5] sigmatropic rearrangement to give the spirocyclobutane of welwitindolinone A, as a single diastereomer. Damn nice!
I’m also glad to read they admit that the selectivity of the latter process was unknown to the group, and that they intend to study this further.
Folks, I’ve had to freeze comments and delete the most inflammatory/libellous – by using this blog, and certainly writing commnets, you’ve read the AUP, and agreed to it. It states that the discussion should remain civil, and frankly we’d gone beyond that considerably. Please remember that, especially if you don’t use your real name as your “Name”, I take the flak and indeed the harm to my career prospects when commenters are libellous. I’ll open the comments again shortly, and allow you to re-write your comment then – with your real name attached – if you still think it’s a good idea.
To paraphrase the great Michael Winner “Calm-down dear…. It’s only a synthesis paper!”