Field of Science

Carbene 'decarbenized'

An interesting exchange has taken place in the pages of Angewandte Chemie. Barbel Shulze and his group at the University of Leipzig claimed that they had isolated the first isothiazolium carbenoid (DOI: 10.1002/anie.200702746)

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Other carbenoids such as imidalolium, thiazolium etc. were already well known. The group characterised this elusive species by solid state NMR and cited the C13 resonance of the carbenoid carbon as proof that they had it in hand. However, they had no crystal structure

One of their "proofs" for the existence of this species was its reaction with morpholine, in which they suggested that the carbene inserts into the morpholino NH in a classic carbene insertion reaction.

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However, Guy Bertrand and his group at UC Riverside challenged this assumption and pretty clearly negated it as far as I can see.(DOI: 10.1002/anie.200702272) They showed that the purported carbene actually forms a different species.

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Very nicely, they got a hint for this process from an old 1966 Woodward publication dealing with ring opening of isoxazolium salts. I love such insights from history!

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Interestingly, their calculations, done at a pretty decent level of quantum chemical theory, suggested the TS for this rearrangement was only 1 kcal/mol more than the purported carbene, this making its existence almost impossible. And the rearranged derivative was several kcal/mol more stable than the purported carbene. Thus their rebuttual clearly says that not only do they think the carbene is not "stable" but they don't observe it at all.

The group also proposed an alternative explanation for the formation of the morpholino derivative, a simple nucleophilic addition to an electrophilic carbon (6S below). Not only that, but they also obtained a crystal structure for product (7s below) of the reaction of the morpholine with their new rearranged derivative.

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In my opinion, Bertrand's group cinched it as well as it can be cinched. I wouldn't have liked to be Shulze in this whole episode. Now anybody can make a mistake, although one would prefer that he or she does not make it in the pages of AC. But at the same time, what is most troublesome is the fact that Bertrand and his colleagues could not observe the NMR resonance that Shulz and his colleagues observed. Not at all.

Now one thing to Schulze's credit is that he and his co-authors graciously accepted Bertrand's alternative explanation which was pretty solid and were generous in their praise of his group's work. However, they also challenge Bertrand's alternative explanation of the formation of the morpholino derivative; after all, both nucleophilic addition and carbene insertion could lead to the same product.

But what's happening here? What exactly did the earlier group see? Only time will tell I guess. Maybe some even more interesting chemistry will be unearthed. I guess an elusive species has to pass some pretty rigorous tests in order to be called "stable".

P.S. Nothing like mulling over and reading an interesting chemistry debate while listening to Mozart's 40th Symphony


  1. Cool!
    Nothing but love for crystal structures...

  2. "What you can touch and what you can see, is all that your world will ever be"


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