Lukas, who occasionally comments on this blog, sent me the following challenge. In a recent article he had proposed that the stereochemical outcome (Z) of reaction between a butenal and thioacetic acid as shown below arose by an unusual concerted cycloaddtion involving an S-H bond. He wrote in the article “…this scheme … recommends itself for evaluation by in silico methods“. I asked if the answer could be posted here, and he agreed. So here it is.
My initial instinct was that it might prove to be a reaction with “hidden intermediates” (for example transfer of the S-H proton onto the oxygen to form a zwitterionic “hidden intermediate”). Well, this is what the computed transition state and the IRC look like.
- For acrolein itself, the forward free-energy barrier ΔG†298 is 25.8 kcal/mol (ωB97XD/6-311G(d,p)/SCRF=acetone) and the reverse barrier 27.7 kcal/mol, which makes the overall free energy for the reaction -1.8 kcal/mol. These values are not inconsistent with an equilibrium thermal reaction at room temperatures or above.
- The gradients show no sign of any “hidden intermediates”. The reaction indeed is nicely concerted, albeit with O-H bond formation asynchronously preceding that of C-S. This reaction should indeed be added to the pantheon of facile pericyclic (or pseudopericyclic) reaction types.
- For the methyl substituted system (R=Me) the forward barrier is a little lower than before (23.8 kcal/mol) and the reverse likewise (25.5).‡ The (Z) product far dominates the (E) (61:1). The IRC is similar to the unsubstituted reaction, but with the faintest of hints of a hidden intermediate (at IRC ~0.8).
The reaction itself is a smaller-ring thia-homologue of one reported by Birney and classified there as a pseudopericyclic reaction, the point of interest being the difference in behaviour between the O-H acid and the S-H acid.
Well, that is the in silico counterpart to the in silica experiment. It took a few hours (about the same as a few NMR measurements?).
‡Slightly lower values are obtained for the s-cis conformation of the thio-acid: ΔG†298 is 21.0 kcal/mol for the forward and 22.0 for the reverse reactions.
- L. Hintermann, and A. Turočkin, "Reversible Generation of Metastable Enols in the 1,4-Addition of Thioacetic Acid to α,β-Unsaturated Carbonyl Compounds", The Journal of Organic Chemistry, vol. 77, pp. 11345-11348, 2012. http://dx.doi.org/10.1021/jo3021709
- Henry S. Rzepa., "Gaussian Job Archive for C5H8O2S", 2013. http://dx.doi.org/10.6084/m9.figshare.701466
- Henry S. Rzepa., "Gaussian Job Archive for C5H8O2S", 2013. http://dx.doi.org/10.6084/m9.figshare.701174
- Henry S. Rzepa., "Gaussian Job Archive for C6H10O2S", 2013. http://dx.doi.org/10.6084/m9.figshare.701467
- Henry S. Rzepa., "Gaussian Job Archive for C6H10O2S", 2013. http://dx.doi.org/10.6084/m9.figshare.701468
- H. Ji, L. Li, X. Xu, S. Ham, L.A. Hammad, and D.M. Birney*, "Multiphoton Infrared Initiated Thermal Reactions of Esters: Pseudopericyclic Eight-Centeredcis-Elimination", Journal of the American Chemical Society, vol. 131, pp. 528-537, 2009. http://dx.doi.org/10.1021/ja804812c
- Henry S. Rzepa., "Gaussian Job Archive for C6H10O2S", 2013. http://dx.doi.org/10.6084/m9.figshare.701501
Tags: Reaction Mechanism