B.R.S.M. When all you have is a hammer everything looks like a nail


Welwitindolinones Redux

Perhaps not unexpectedly, given last year's exciting breakthrough syntheses, more synthetic work on the weltwitindolinones appeared in the literature last week, so I think an update is in order. As a reminder, the first synthesis of a bridged bicyclic member of this family came in March last year when Rawal reported a neat racemic route to N-methylwelwitindolinone D isonitrile, emerging as the winner of a 15 year race between plenty of well known synthetic chemists. This was rapidly followed by Garg, who published an excellent synthesis of (-)-N-methylwelwitindolinone C isothiocyanate in August, which I covered here.

Well, two more back to back JACS papers,[1] one each from Rawal and Garg have just appeared, and I'll summarise both here. Garg's describes improvements to the key step in his previously reported route to (-)-N-methylwelwitindolinone C isothiocyanate, along with the synthesis of (-)-N-methylwelwitindolinone C isonitrile and a couple of the so-called 'oxidised welwitindolinones'. Rawal's contains an asymmetric version of his previous racemic route, allowing access to (-)-N-methylwelwitindolinone C isothiocyanate/isonitrile, along with one of the 'oxidised welwitindolinones'. As Rawal’s has the most new chemistry of the two we'll look at that first.

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(–)-N-Methylwelwitindolinone C Isothiocyanate

Update: 13/09/11. I have reworded the introduction considerably as the original version of this paragraph described work by Rawal and coworkers in this area unfairly. Having reread the papers and what I'd written I couldn't leave things as they were. The original text can be found in [5] at the end of the article.

Sorry things have been so quiet around here lately - moving out of the flat I've lived in for the past three years, having no internet and applying for conferences have made blogging tricky. I was a bit worried that someone'd beat me to this as it's such a nice bit of work, and Tot. Syn. did on Sunday, but I'd mostly finished this by then, so here's my take anyway.

Total Synthesis of (–)-N-Methylwelwitindolinone C Isothiocyanate

Garg et al., J. Am. Chem. Soc., 2011, ASAP; [PDF][SI][GROUP]

DOI: 10.1021/ja206538k

There's been a lot of interest in these unusual looking natural products in the past decade with publications from Wood, Trost, Baran, Simpkins, Martin and Rawal all appearing in the literature. Credit for the first total synthesis of a member of this family goes to Rawal and coworkers, who reported a neat route to racemic N-methylwelwitindolinone D isonitrile back in March of this year, unfortunately before I'd started this blog.[1,2] This paper by Garg describes the first synthesis of N-methylwelwitindolinone C isothiocyanate to date, using a chiral pool based approach from (S)-carvone, and also contains lots of interesting chemistry.

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