Unexpected Isomerization of Oxetane-Carboxylic Acids – substrate design.

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.

R’ is set to have three values, R’=H (the original substituent), R’= CH3 and R’= CF3 (FAIR data DOI: 10.14469/hpc/10820)

R’ ΔG, kcal/mol
H 27.0
CH3 29.1
CF3 39.6

The inference is clear-cut; to inhibit the isomerisation to a lactone, CF3 groups substituted onto the methylene groups of the oxetane will effectively do this, with CH3 itself having a much weaker effect.


DOI: 10.14469/hpc/10861 and 10.14469/hpc/10862


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. http://dx.doi.org/10.1021/acs.orglett.2c01402

One Response to “
Unexpected Isomerization of Oxetane-Carboxylic Acids – substrate design.

  1. Henry Rzepa says:

    I have also now added a Me at the bridgehead position. The free energy barrier was 29.2 kcal/, pretty much the same as adding the methyl to the methylene gorups.

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