Henry Rzepa's Blog

The topic of dicarbon, C₂, has been discussed here for a few years now. It undoubtedly would be a gas! This aspect of the species came to the fore recently[1] when further experiments on a potential chemical precursor of dicarbon, the zwitterion X(+)-C≡C(-), showed that different variants of X(+), such as not only X=PhI(+), but also e.g. X=dibenzothiophenium(+) appeared to generate a gaseous species, which could be trapped as “C₂” in a solvent-free connected flask experiment.

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References

1. H.S. Rzepa, M. Arita, K. Miyamoto, and M. Uchiyama, "A combined DFT-predictive and experimental exploration of the sensitivity towards nucleofuge variation in zwitterionic intermediates relating to mechanistic models for unimolecular chemical generation and trapping of free C ₂ and alternative bimolecular pathways involving no free C ₂", Physical Chemistry Chemical Physics, vol. 24, pp. 25816-25821, 2022. https://doi.org/10.1039/d2cp01214f

The term bispericyclic reaction was famously coined by Caramella et al in 2002[1] to describe the unusual features of the apparently innocuous dimerisation of cyclopentadiene. It shows features of two paths for different pericyclic reactions, comprising a 2+4 cycloaddition in the early stages, but evolving into a (degenerate) pair of [3,3] sigmatropic reactions in the latter stages. Houk (who also uses the term ambimodal) has in recent years extended the number of examples of such pericyclic sequences to trispericyclic[2] (see here) and even an ambimodel tetrapericyclic reaction, as reported at the recent WATOC event. Here I show an example of a new type of bispericyclic reaction, comprising a 2+4 cycloaddition combined with a electrocyclic ring opening.

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References

1. P. Caramella, P. Quadrelli, and L. Toma, "An Unexpected Bispericyclic Transition Structure Leading to 4+2 and 2+4 Cycloadducts in the <i>E</i><i>ndo</i> Dimerization of Cyclopentadiene", Journal of the American Chemical Society, vol. 124, pp. 1130-1131, 2002. https://doi.org/10.1021/ja016622h
2. X. Xue, C.S. Jamieson, M. Garcia-Borràs, X. Dong, Z. Yang, and K.N. Houk, "Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity", Journal of the American Chemical Society, vol. 141, pp. 1217-1221, 2019. https://doi.org/10.1021/jacs.8b12674

Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer chain, via a H-bonded dimer shown below.

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Having established a viable model for the unexpected isomerism of oxetane carboxylic acids to lactones[1], and taken a look at a variation in the proton transfer catalyst needed to accomplish the transformation, I now investigate the substrate itself.

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References

1. B. Chalyk, A. Grynyova, K. Filimonova, T.V. Rudenko, D. Dibchak, and P.K. Mykhailiuk, "Unexpected Isomerization of Oxetane-Carboxylic Acids", Organic Letters, vol. 24, pp. 4722-4728, 2022. https://doi.org/10.1021/acs.orglett.2c01402

Derek Lowe’s blog has a recent post entitled A Downside to Oxetane Acids which picks up on a recent article[1] describing how these acids are unexpectedly unstable, isomerising to a lactone at a significant rate without the apparent need for any catalyst. This is important because these types of compound occur frequently in the medicinal chemistry literature.

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References

1. B. Chalyk, A. Grynyova, K. Filimonova, T.V. Rudenko, D. Dibchak, and P.K. Mykhailiuk, "Unexpected Isomerization of Oxetane-Carboxylic Acids", Organic Letters, vol. 24, pp. 4722-4728, 2022. https://doi.org/10.1021/acs.orglett.2c01402