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Totally Synthetic by Paul H. Docherty, 27 March 2007

Total Synthesis of Welwitindolinone & Fischerindole


P. S. Baran, T. J. Maimone, J. M. 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 the total synthesis of 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. A very nice total synthesis!

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.