Posts Tagged ‘X-ray’

Chiroptical spectroscopy of the natural product Steganone.

Tuesday, February 10th, 2015
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Steganone is an unusual natural product, known for about 40 years now. The assignment of its absolute configurations makes for an interesting, on occasion rather confusing, and perhaps not entirely atypical story. I will start with the modern accepted stereochemical structure of this molecule, which comes in the form of two separately isolable atropisomers.
steganone
The first reported synthesis of this system in 1977 was racemic, and no stereochemistry is shown in the article (structure 2).[1] Three years later an “Asymmetric total synthesis of (-)steganone and revision of its absolute configuration” shows how the then accepted configuration (structure 1 in this article) needs to be revised to the enantiomer shown as structure 12 in the article[2] and matching the above representation. The system has continued to attract interest ever since[3],[4],[5],[6], not least because of the presence of axial chirality in the form of atropisomerism. Thus early on it was shown that the alternative atropisomer, the (aS,R,R) configuration initially emerges out of several syntheses, and has to be converted to the (aR,R,R) configuration by heating[3]. One could easily be fooled by such isomerism!

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References

  1. D. Becker, L.R. Hughes, and R.A. Raphael, "Total synthesis of the antileukaemic lignan (�)-steganacin", Journal of the Chemical Society, Perkin Transactions 1, pp. 1674, 1977. http://dx.doi.org/10.1039/P19770001674
  2. J. Robin, O. Gringore, and E. Brown, "Asymmetric total synthesis of the antileukaemic lignan precursor (-)steganone and revision of its absolute configuration", Tetrahedron Letters, vol. 21, pp. 2709-2712, 1980. http://dx.doi.org/10.1016/S0040-4039(00)78586-8
  3. E.R. Larson, and R.A. Raphael, "Synthesis of (?)-steganone", Journal of the Chemical Society, Perkin Transactions 1, pp. 521, 1982. http://dx.doi.org/10.1039/P19820000521
  4. A. Bradley, W.B. Motherwell, and F. Ujjainwalla, "A concise approach towards the synthesis of steganone analogues", Chemical Communications, pp. 917-918, 1999. http://dx.doi.org/10.1039/A900743A
  5. M. Uemura, A. Daimon, and Y. Hayashi, "An asymmetric synthesis of an axially chiral biaryl via an (arene)chromium complex: formal synthesis of (?)-steganone", Journal of the Chemical Society, Chemical Communications, pp. 1943, 1995. http://dx.doi.org/10.1039/C39950001943
  6. B. Yalcouye, S. Choppin, A. Panossian, F.R. Leroux, and F. Colobert, "A Concise Atroposelective Formal Synthesis of (-)-Steganone", European Journal of Organic Chemistry, vol. 2014, pp. 6285-6294, 2014. http://dx.doi.org/10.1002/ejoc.201402761

The 5σ-confidence level: how much chemistry achieves this?

Saturday, July 5th, 2014
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I was lucky enough to attend the announcement made in 2012 of the discovery of the Higgs Boson. It consisted of a hour-long talk mostly about statistics, and how the particle physics community can only claim a discovery when their data has achieved a 5σ confidence level. This represents a 1 in 3.5 million probability of the result occurring by chance. I started thinking: how much chemistry is asserted at that level of confidence? Today, I read Steve Bachrach’s post on the structure of Citrinalin B and how “use of Goodman’s DP4 method indicates a 100% probability that the structure of citrinalin B is (the structure below)”. Wow, that is even higher than the physicists. Of course, 100% has been obtained by rounding 99.7 (3σ is 99.73%) or whatever (this is one number that should never be so rounded!). pc But there was one aspect of this that I did want to have a confidence level for; the absolute configuration of citrinalin B. Reading the article Steve quotes[1], one sees this aspect is attributed to ref 5[2], dating from 2005. There the configuration was assigned on the basis of “comparison of the electronic circular dichroism (ECD) spectra for 1 and 2 with those of known spirooxiindole alkaloids“. However, this method can fail[3]. Also, one finds “comparison of the vibrational circular dichroism (VCD) spectra of 1 with those of model compounds[2]. Nowadays, one would say that there is no need for model compounds, why not measure and compute the VCD of the actual compound? Even a determination using the Flack crystallographic method can occasionally be wrong![4]. Which leads to asking what typical confidence levels might be for these three techniques, and indeed whether improving instrumentation means that the confidence level gets higher with time. OK, I am going to guess these.

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References

  1. E.V. Mercado-Marin, P. Garcia-Reynaga, S. Romminger, E.F. Pimenta, D.K. Romney, M.W. Lodewyk, D.E. Williams, R.J. Andersen, S.J. Miller, D.J. Tantillo, R.G.S. Berlinck, and R. Sarpong, "Total synthesis and isolation of citrinalin and cyclopiamine congeners", Nature, vol. 509, pp. 318-324, 2014. http://dx.doi.org/10.1038/nature13273
  2. T. Mugishima, M. Tsuda, Y. Kasai, H. Ishiyama, E. Fukushi, J. Kawabata, M. Watanabe, K. Akao, and J. Kobayashi, "Absolute Stereochemistry of Citrinadins A and B from Marine-Derived Fungus", J. Org. Chem., vol. 70, pp. 9430-9435, 2005. http://dx.doi.org/10.1021/jo051499o
  3. F. Cherblanc, Y. Lo, E. De Gussem, L. Alcazar-Fuoli, E. Bignell, Y. He, N. Chapman-Rothe, P. Bultinck, W.A. Herrebout, R. Brown, H.S. Rzepa, and M.J. Fuchter, "On the Determination of the Stereochemistry of Semisynthetic Natural Product Analogues using Chiroptical Spectroscopy: Desulfurization of Epidithiodioxopiperazine Fungal Metabolites", Chemistry - A European Journal, vol. 17, pp. 11868-11875, 2011. http://dx.doi.org/10.1002/chem.201101129
  4. F.L. Cherblanc, Y. Lo, W.A. Herrebout, P. Bultinck, H.S. Rzepa, and M.J. Fuchter, "Mechanistic and Chiroptical Studies on the Desulfurization of Epidithiodioxopiperazines Reveal Universal Retention of Configuration at the Bridgehead Carbon Atoms", J. Org. Chem., vol. 78, pp. 11646-11655, 2013. http://dx.doi.org/10.1021/jo401316a

The subtle effect of dispersion forces on the shapes of molecules: benzyl magnesium bromide.

Sunday, November 10th, 2013
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In the previous post I mentioned in passing the Grignard reagent benzyl magnesium bromide as having tetrahedral coordination at Mg. But I have now noticed, largely through spotting Steve Bachrach’s post on “Acene dimers – open or closed?” another geometric effect perhaps worthy of note, certainly one not always noted in the past; that of dispersion forces.

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A short non-bonding H…H interaction (continued)

Wednesday, October 2nd, 2013
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This is a continuation of the discussion started on Steve Bachrach’s blog about a molecule with a very short H…H interaction involving two Si-H groups with enforced proximity. It had been inferred from the X-ray structure[1] that the H…H distance was in the region of 1.50Å. It’s that cis-butene all over again! So is that H…H region a bond? Is it attractive or repulsive? Go read Steve’s blog first.

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References

  1. J. Zong, J.T. Mague, and R.A. Pascal, " Exceptional Steric Congestion in an in , in -Bis(hydrosilane) ", J. Am. Chem. Soc., vol. 135, pp. 13235-13237, 2013. http://dx.doi.org/10.1021/ja407398w

X-ray analysis and absolute configuration determination using porous complexes.

Wednesday, April 17th, 2013
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This is another in the occasional series of “what a neat molecule”. In this case, more of a “what a neat idea”. The s-triazine below, when coordinated to eg ZnI2, forms what is called a metal-organic-framework, or MOF. A recent article[1] shows how such frameworks can be used to help solve a long-standing problem in structure determination, how to get a crystal structure on a compound that does not crystallise on its own.

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References

  1. Y. Inokuma, S. Yoshioka, J. Ariyoshi, T. Arai, Y. Hitora, K. Takada, S. Matsunaga, K. Rissanen, and M. Fujita, "X-ray analysis on the nanogram to microgram scale using porous complexes", Nature, vol. 495, pp. 461-466, 2013. http://dx.doi.org/10.1038/nature11990

To be cyclobutadiene, or not to be, that is the question? You decide.

Thursday, March 21st, 2013
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A quartet of articles has recently appeared on the topic of cyclobutadiene.[1],[2],[3],[4]. You will find a great deal discussed there, but I can boil it down to this essence. Do the following coordinates (obtained from a (disordered) previously published[5] x-ray refinement) correspond to a van der Waals complex of 1,3-dimethyl cyclobutadiene and carbon dioxide, or do they instead represent a covalent interaction between these two components resulting in a compound with the chemical name 2-oxabicyclo[2.2.0]hex-5-en-3-one (i.e. not a cyclobutadiene)?

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References

  1. H.S. Rzepa, "A Computational Evaluation of the Evidence for the Synthesis of 1,3-Dimethylcyclobutadiene in the Solid State and Aqueous Solution", Chemistry - A European Journal, vol. 19, pp. 4932-4937, 2013. http://dx.doi.org/10.1002/chem.201102942
  2. M. Shatruk, and I.V. Alabugin, "Reinvestigation of “Single-Crystal X-ray Structure of 1,3-dimethylcyclobutadiene”", Chemistry - A European Journal, vol. 19, pp. 4942-4945, 2013. http://dx.doi.org/10.1002/chem.201103017
  3. Y. Legrand, D. Dumitrescu, A. Gilles, E. Petit, A. van der Lee, and M. Barboiu, "A Constrained Disorder Refinement: “Reinvestigation of “Single-Crystal X-ray Structure of 1,3-Dimethylcyclobutadiene” by M. Shatruk and I. V. Alabugin”", Chemistry - A European Journal, vol. 19, pp. 4946-4950, 2013. http://dx.doi.org/10.1002/chem.201203234
  4. Y. Legrand, D. Dumitrescu, A. Gilles, E. Petit, A. van der Lee, and M. Barboiu, "Reply to A Computational Evaluation of the Evidence for the Synthesis of 1,3-Dimethylcyclobutadiene in Solid State and Aqueous Solution-Beyond the Experimental Reality", Chemistry - A European Journal, vol. 19, pp. 4938-4941, 2013. http://dx.doi.org/10.1002/chem.201203235
  5. Y. Legrand, A. van der Lee, and M. Barboiu, "Single-Crystal X-ray Structure of 1,3-Dimethylcyclobutadiene by Confinement in a Crystalline Matrix", Science, vol. 329, pp. 299-302, 2010. http://dx.doi.org/10.1126/science.1188002

Helically conjugated molecules. A follow-up to [144]-annulene.

Tuesday, February 12th, 2013
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An extensive discussion developed regarding my post on a fascinating helical [144]-annulene. Topics included the nature of the ring current sustained by the π-electrons and in particular the bond-length alternation around the periphery and whether this should alter if the electron count were to be changed to that of a 4n+2 system (i.e. a dication). Whilst the [144]-annulene itself is hypothetical, it emerged that some compounds known as expanded porphyrins have very similar (albeit smaller scale) helical structures. X-ray structures for two such provide useful reality checks on the calculations. Here‡ I include the (3D) coordinates of these two systems so that you can explore for yourself their helicity.

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σ-π-Conjugation: seeking evidence by a survey of crystal structures.

Sunday, February 3rd, 2013
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The electronic interaction between a single bond and an adjacent double bond is often called σ-π-conjugation (an older term for this is hyperconjugation), and the effect is often used to e.g. explain why more highly substituted carbocations are more stable than less substituted ones. This conjugation is more subtle in neutral molecules, but following my use of crystal structures to explore the so-called gauche effect (which originates from σ-σ-conjugation), I thought I would have a go here at seeing what the crystallographic evidence actually is for the σ-π-type.

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Alkyne metathesis: a comparison with alkene metathesis.

Monday, October 8th, 2012
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Metathesis reactions are a series of catalysed transformations which transpose the atoms in alkenes or alkynes. Alkyne metathesis is closely related to the same reaction for alkenes, and one catalyst that is specific to alkynes was introduced by Schrock (who with Grubbs won the Nobel prize for these discoveries) and is based on tungsten (M=W(OR)3).

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Streptomycin: a case study in the progress of science.

Monday, May 28th, 2012
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Streptomycin is an antibiotic active against tuberculosis, and its discovery has become something of a cause célèbre. It was first isolated on October 19, 1943 by a graduate student Albert Schatz in the laboratory of Selman Waksman at Rutgers University. I want to concentrate in this post on its molecular structure. Its initial isolation was followed by an extraordinarily concentrated period of about three years devoted to identifying that structure, culminating in a review of this chemistry in 1948 by Lemieux and Wolfram.[1] This review presents the structure as shown below (left). The modern rendering on the right is based on a crystal structure done in 1978.[2]

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References

  1. R. Lemieux, and M. Wolfrom, "The Chemistry of Streptomycin", Advances in Carbohydrate Chemistry, pp. 337-384, 1948. http://dx.doi.org/10.1016/S0096-5332(08)60034-X
  2. S. Neidle, D. Rogers, and M.B. Hursthouse, "The Crystal and Molecular Structure of Streptomycin Oxime Selenate Tetrahydrate", Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, vol. 359, pp. 365-388, 1978. http://dx.doi.org/10.1098/rspa.1978.0047