Henry Rzepa's Blog Chemistry with a twist

May 2, 2019

An Ambimodal Trispericyclic Transition State: the effect of solvation?

Ken Houk’s group has recently published this study of cycloaddition reactions, using a combination of classical transition state location followed by molecular dynamics trajectory calculations,[1] and to which Steve Bachrach’s blog alerted me. The reaction struck me as being quite polar (with cyano groups) and so I took a look at the article to see what both the original[2] experimental conditions were and how the new simulations compared. The reaction itself is shown below.

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References

  1. 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. http://dx.doi.org/10.1021/jacs.8b12674
  2. C.Y. Liu, and S.T. Ding, "Cycloadditions of electron-deficient 8,8-disubstituted heptafulvenes to electron-rich 6,6-disubstituted fulvenes", The Journal of Organic Chemistry, vol. 57, pp. 4539-4544, 1992. http://dx.doi.org/10.1021/jo00042a039

April 25, 2019

Imaging normal vibrational modes of a single molecule of CoTPP: a mystery about the nature of the imaged species.

Previously, I explored (computationally) the normal vibrational modes of Co(II)-tetraphenylporphyrin (CoTPP) as a “flattened” species on copper or gold surfaces for comparison with those recently imaged[1]. The initial intent was to estimate the “flattening” energy. There are six electronic possibilities for this molecule on a metal surface. Respectively positively, or negatively charged and a neutral species, each in either a low or a high-spin electronic state. I reported five of these earlier, finding each had quite high barriers for “flattening” the molecule. For the final 6th possibility, the triplet anion, the SCF (self-consistent-field) had failed to converge, but for which I can now report converged results.

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References

  1. J. Lee, K.T. Crampton, N. Tallarida, and V.A. Apkarian, "Visualizing vibrational normal modes of a single molecule with atomically confined light", Nature, vol. 568, pp. 78-82, 2019. http://dx.doi.org/10.1038/s41586-019-1059-9

April 18, 2019

Imaging vibrational normal modes of a single molecule.

The topic of this post originates from a recent article which is attracting much attention.[1] The technique uses confined light to both increase the spatial resolution by around three orders of magnitude and also to amplify the signal from individual molecules to the point it can be recorded. To me, Figure 3 in this article summarises it nicely (caption: visualization of vibrational normal modes). Here I intend to show selected modes as animated and rotatable 3D models with the help of their calculation using density functional theory (a mode of presentation that the confinement of Figure 3 to the pages of a conventional journal article does not enable).

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References

  1. J. Lee, K.T. Crampton, N. Tallarida, and V.A. Apkarian, "Visualizing vibrational normal modes of a single molecule with atomically confined light", Nature, vol. 568, pp. 78-82, 2019. http://dx.doi.org/10.1038/s41586-019-1059-9

April 4, 2019

Smoke and mirrors. All is not what it seems with this Sn2 reaction!

Previously, I explored the Graham reaction to form a diazirine. The second phase of the reaction involved an Sn2′ displacement of N-Cl forming C-Cl. Here I ask how facile the simpler displacement of C-Cl by another chlorine might be and whether the mechanism is Sn2 or the alternative Sn1. The reason for posing this question is that as an Sn1 reaction, simply ionizing off the chlorine to form a diazacyclopropenium cation might be a very easy process. Why? Because the resulting cation is analogous to the cyclopropenium cation, famously proposed by Breslow as the first example of a 4n+2 aromatic ring for which the value of n is zero and not 1 as for benzene.[1] Another example of a famous “Sn1” reaction is the solvolysis of t-butyl chloride to form the very stable tertiary carbocation and chloride anion (except in fact that it is not an Sn1 reaction but an Sn2 one!)

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References

  1. R. Breslow, "SYNTHESIS OF THE s-TRIPHENYLCYCLOPROPENYL CATION", Journal of the American Chemical Society, vol. 79, pp. 5318-5318, 1957. http://dx.doi.org/10.1021/ja01576a067

April 1, 2019

Impossible molecules.

Members of the chemical FAIR data community have just met in Orlando (with help from the NSF, the American National Science Foundation) to discuss how such data is progressing in chemistry. There are a lot of themes converging at the moment. Thus this article[1] extolls the virtues of having raw NMR data available in natural product research, to which we added that such raw data should also be made FAIR (Findable, Accessible, Interoperable and Reusable) by virtue of adding rich metadata and then properly registering it so that it can be searched. These themes are combined in another article which made a recent appearance.[2]

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References

  1. J.B. McAlpine, S. Chen, A. Kutateladze, J.B. MacMillan, G. Appendino, A. Barison, M.A. Beniddir, M.W. Biavatti, S. Bluml, A. Boufridi, M.S. Butler, R.J. Capon, Y.H. Choi, D. Coppage, P. Crews, M.T. Crimmins, M. Csete, P. Dewapriya, J.M. Egan, M.J. Garson, G. Genta-Jouve, W.H. Gerwick, H. Gross, M.K. Harper, P. Hermanto, J.M. Hook, L. Hunter, D. Jeannerat, N. Ji, T.A. Johnson, D.G.I. Kingston, H. Koshino, H. Lee, G. Lewin, J. Li, R.G. Linington, M. Liu, K.L. McPhail, T.F. Molinski, B.S. Moore, J. Nam, R.P. Neupane, M. Niemitz, J. Nuzillard, N.H. Oberlies, F.M.M. Ocampos, G. Pan, R.J. Quinn, D.S. Reddy, J. Renault, J. Rivera-Chávez, W. Robien, C.M. Saunders, T.J. Schmidt, C. Seger, B. Shen, C. Steinbeck, H. Stuppner, S. Sturm, O. Taglialatela-Scafati, D.J. Tantillo, R. Verpoorte, B. Wang, C.M. Williams, P.G. Williams, J. Wist, J. Yue, C. Zhang, Z. Xu, C. Simmler, D.C. Lankin, J. Bisson, and G.F. Pauli, "The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research", Natural Product Reports, vol. 36, pp. 35-107, 2019. http://dx.doi.org/10.1039/c7np00064b
  2. A. Barba, S. Dominguez, C. Cobas, D.P. Martinsen, C. Romain, H.S. Rzepa, and F. Seoane, "Workflows Allowing Creation of Journal Article Supporting Information and Findable, Accessible, Interoperable, and Reusable (FAIR)-Enabled Publication of Spectroscopic Data", ACS Omega, vol. 4, pp. 3280-3286, 2019. http://dx.doi.org/10.1021/acsomega.8b03005

March 24, 2019

The shortest known CF…HO hydrogen bond.

There is a predilection amongst chemists for collecting records; one common theme is the length of particular bonds, either the shortest or the longest. A particularly baffling type of bond is that between the very electronegative F atom and an acid hydrogen atom such as that in OH. Thus short C-N…HO hydrogen bonds are extremely common, as are C-O…HO. But F atoms in C-F bonds are largely thought to be inert to hydrogen bonding, as indicated by the use of fluorine in many pharmaceuticals as inert isosteres.[1] Here I do an up-to-date search of the CSD crystal structure database, which is now on the verge of accumulating 1 million entries, to see if any strong C-F…HO hydrogen bonding may have been recently discovered.

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References

  1. S. Purser, P.R. Moore, S. Swallow, and V. Gouverneur, "Fluorine in medicinal chemistry", Chem. Soc. Rev., vol. 37, pp. 320-330, 2008. http://dx.doi.org/10.1039/B610213C

February 18, 2019

The Graham reaction: Deciding upon a reasonable mechanism and curly arrow representation.

Students learning organic chemistry are often asked in examinations and tutorials to devise the mechanisms (as represented by curly arrows) for the core corpus of important reactions, with the purpose of learning skills that allow them to go on to improvise mechanisms for new reactions. A common question asked by students is how should such mechanisms be presented in an exam in order to gain full credit? Alternatively, is there a single correct mechanism for any given reaction? To which the lecturer or tutor will often respond that any reasonable mechanism will receive such credit. The implication is that a mechanism is “reasonable” if it “follows the rules”. The rules are rarely declared fully, but seem to be part of the absorbed but often mysterious skill acquired in learning the subject. These rules also include those governing how the curly arrows should be drawn. Here I explore this topic using the Graham reaction.[1]

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References

  1. W.H. Graham, "The Halogenation of Amidines. I. Synthesis of 3-Halo- and Other Negatively Substituted Diazirines1", Journal of the American Chemical Society, vol. 87, pp. 4396-4397, 1965. http://dx.doi.org/10.1021/ja00947a040

January 13, 2019

Free energy relationships and their linearity: a test example.

Linear free energy relationships (LFER) are associated with the dawn of physical organic chemistry in the late 1930s and its objectives in understanding chemical reactivity as measured by reaction rates and equilibria.

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December 21, 2018

Epoxidation of ethene: a new substituent twist.

Five years back, I speculated about the mechanism of the epoxidation of ethene by a peracid, concluding that kinetic isotope effects provided interesting evidence that this mechanism is highly asynchronous and involves a so-called “hidden intermediate”. Here I revisit this reaction in which a small change is applied to the atoms involved.

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September 20, 2018

Concerted Nucleophilic Aromatic Substitution Mediated by the PhenoFluor Reagent.

Recently, the 100th anniversary of the birth of the famous chemist Derek Barton was celebrated with a symposium. One of the many wonderful talks presented was by Tobias Ritter and entitled “Late-stage fluorination for PET imaging” and this resonated for me. The challenge is how to produce C-F bonds under mild conditions quickly so that 18F-labelled substrates can be injected for the PET imaging. Ritter has several recent articles on this theme which you should read.[1],[2]

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References

  1. P. Tang, W. Wang, and T. Ritter, "Deoxyfluorination of Phenols", Journal of the American Chemical Society, vol. 133, pp. 11482-11484, 2011. http://dx.doi.org/10.1021/ja2048072
  2. C.N. Neumann, and T. Ritter, "Facile C–F Bond Formation through a Concerted Nucleophilic Aromatic Substitution Mediated by the PhenoFluor Reagent", Accounts of Chemical Research, vol. 50, pp. 2822-2833, 2017. http://dx.doi.org/10.1021/acs.accounts.7b00413

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