Posts Tagged ‘CF 3 CO’

Computationally directed synthesis: 2,3-dimethyl-2-butene + NO(+).

Saturday, September 6th, 2014
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In the previous posts, I explored reactions which can be flipped between two potential (stereochemical) outcomes. This triggered a memory from Alex, who pointed out this article from 1999[1] in which the nitrosonium cation as an electrophile can have two outcomes A or B when interacting with the electron-rich 2,3-dimethyl-2-butene. NO NMR evidence clearly pointed to the π-complex A as being formed, and not the cyclic nitrosonium species B (X=Al4). If you are wondering where you have seen an analogy for the latter, it would be the species formed when bromine reacts with an alkene (≡ Br+, X=Br or Br3). The two structures are shown below[1] tetramethyletylene-NO+ Since the topic that sparked this concerned pericyclic reactions, it seemed possible that if it had been formed, species B would immediately undergo a pericyclic electrocyclic reaction to form the rather odd-looking cation C, which might then be trapped by eg X(-) to form the nitrone D. So this post is an exploration of what happens when X-NO (X= CF3COO, trifluoracetate) interacts with 2,3-dimethyl-2-butene, as an illustration of what can be achieved nowadays from about 2 days worth of dry-lab computation as a prelude to e.g. an experiment in the wet-lab (it would take a little more than two days to achieve the latter I suspect). Hence computationally directed synthesis. The model is set up as ωB97XD/6-311G(d,p)/SCRF=chloroform. A transition state is located[2] and the resulting IRC (below) [3] does not quite have the outcome the above scheme would suggest. NOa NOe NOg Neither A nor B is formed; instead it is the tetrahedral species E, which is ~15 kcal/mol endothermic. NOaa I should immediately point out that this is not inconsistent with the formation of A as previously characterised[1]. That is because this experiment was conducted with a non-nucleophilic counter-anion (X=Al4), whereas in the computational simulation above, we have a nucleophilic anion (X= CF3CO2). What a difference the inclusion of a counter-ion in the calculation can have! The barrier however (~35 kcal/mol) is a little too high for a facile thermal reaction. In the second of this two-stage reaction, E now ring-opens to form the anticipated D[4] with quite a small barrier of ~6 kcal/mol, but a highly exothermic outcome. I ask this question about it; can this still be described as a pericyclic process? (there is some analogy to the electrocyclic ring opening of a cyclopropyl tosylate). NObNObe So what are the conclusions? Well, because of the rather high initial barrier, the alkene will need activation (by electron donating substituents, perhaps OMe) for the reaction to become more viable. But if it works, it could be an interesting synthesis of nitrones (I have not yet searched to find out if the reaction is actually known).

References

  1. G.I. Borodkin, I.R. Elanov, A.M. Genaev, M.M. Shakirov, and V.G. Shubin, "Interaction in olefin–NO+ complexes: structure and dynamics of the NO+–2,3-dimethyl-2-butene complex", Mendeleev Communications, vol. 9, pp. 83-84, 1999. http://dx.doi.org/10.1070/MC1999v009n02ABEH000995
  2. Henry S Rzepa., "C8H12F3NO3", 2014. http://dx.doi.org/10.14469/ch/24979
  3. Henry S. Rzepa., "Gaussian Job Archive for C8H12F3NO3", 2014. http://dx.doi.org/10.6084/m9.figshare.1162797
  4. Henry S. Rzepa., "Gaussian Job Archive for C8H12F3NO3", 2014. http://dx.doi.org/10.6084/m9.figshare.1162676

Mechanism of the Boekelheide rearrangement

Wednesday, June 26th, 2013
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A reader asked me about the mechanism of the reaction of 2-picoline N-oxide with acetic anhydride to give 2-acetoxymethylpyridine (the Boekelheide Rearrangement[1]). He wrote ” I don’t understand why the system should prefer to go via fragmentation-recombination (… the evidence being that oxygen labelling shows scrambling) when there is an easy concerted pathway available (… a [3,3]sigmatropic shift). Furthermore, is it possible for two pathways to co-exist?” Here is how computation might enlighten us.

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References

  1. A. Massaro, A. Mordini, A. Mingardi, J. Klein, and D. Andreotti, "A New Sequential Intramolecular Cyclization Based on the Boekelheide Rearrangement", European Journal of Organic Chemistry, vol. 2011, pp. 271-279, 2010. http://dx.doi.org/10.1002/ejoc.201000936

Hidden intermediates in the (acid catalysed) ring opening of propene epoxide.

Monday, May 6th, 2013
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In a previous post on the topic, I remarked how the regiospecific ethanolysis of propene epoxide[1] could be quickly and simply rationalised by inspecting the localized NBO orbital calculated for either the neutral or the protonated epoxide. This is an application of Hammond’s postulate[[2] in extrapolating the properties of a reactant to its reaction transition state. This approach implies that for acid-catalysed hydrolysis, the fully protonated epoxide is a good model for the subsequent transition state. But is this true? Can this postulate be tested? Here goes.

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References

  1. H.C. Chitwood, and B.T. Freure, "The Reaction of Propylene Oxide with Alcohols", Journal of the American Chemical Society, vol. 68, pp. 680-683, 1946. http://dx.doi.org/10.1021/ja01208a047
  2. G.S. Hammond, "A Correlation of Reaction Rates", Journal of the American Chemical Society, vol. 77, pp. 334-338, 1955. http://dx.doi.org/10.1021/ja01607a027