December 20th, 2012
I have written earlier about dihydrocostunolide, and how in 1963 Corey missed spotting the electronic origins of a key step in its synthesis.[1]. A nice juxtaposition to this failed opportunity relates to Woodward’s project at around the same time to synthesize vitamin B12. The step in the synthesis that caused him to ponder is shown below.
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References
- E.J. Corey, and A.G. Hortmann, "The Total Synthesis of Dihydrocostunolide", Journal of the American Chemical Society, vol. 87, pp. 5736-5742, 1965. https://doi.org/10.1021/ja00952a037
Tags: dispersion energy, free energy, Historical, pericyclic
Posted in Interesting chemistry, pericyclic, reaction mechanism | No Comments »
December 19th, 2012
The Sharpless epoxidation of an allylic alcohol had a big impact on synthetic chemistry when it was introduced in the 1980s, and led the way for the discovery (design?) of many new asymmetric catalytic systems. Each achieves its chiral magic by control of the geometry at the transition state for the reaction, and the stabilizations (or destabilizations) that occur at that geometry. These in turn can originate from factors such as stereoelectronic control or simply by the overall sum of many small attractions and repulsions we call dispersion interactions. Here I take an initial look at these for the binuclear transition state shown schematically below.
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Tags: asymmetric catalytic systems, Bob Hanson, catalysis, Julia Contreras-Garcia, little web site, NCI, non-covalent-analysis, Reaction Mechanism, terminal =CH
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December 17th, 2012
Part one on this topic showed how a quantum mechanical model employing just one titanium centre was not successful in predicting the stereochemical outcome of the Sharpless asymmetric epoxidation. Here in part 2, I investigate whether a binuclear model might have more success. The new model is constructed using two units of Ti(OiPr)4, which are likely to assemble into a dimer such as that shown below (in this crystal structure, some of the iPr groups are perfluorinated).
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Tags: catalysis, catalytic metal centre, Enantioselective, free energy difference, Reaction Mechanism, Sharpless epoxidation, t-butyl, This free energy difference, Tutorial material
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December 9th, 2012
Sharpless epoxidation converts a prochiral allylic alcohol into the corresponding chiral epoxide with > 90% enantiomeric excess[1],[2]. Here is the first step in trying to explain how this magic is achieved.
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References
- J.M. Klunder, S.Y. Ko, and K.B. Sharpless, "Asymmetric epoxidation of allyl alcohol: efficient routes to homochiral .beta.-adrenergic blocking agents", The Journal of Organic Chemistry, vol. 51, pp. 3710-3712, 1986. https://doi.org/10.1021/jo00369a032
- R.M. Hanson, and K.B. Sharpless, "Procedure for the catalytic asymmetric epoxidation of allylic alcohols in the presence of molecular sieves", The Journal of Organic Chemistry, vol. 51, pp. 1922-1925, 1986. https://doi.org/10.1021/jo00360a058
Tags: animation, asymmetric epoxidation, catalysis, Enantioselective, free energy, lower energy conformations, Reaction Mechanism, Tutorial material
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December 4th, 2012
Birch reduction of benzene itself results in 1,4-cyclohexadiene rather than the more stable (conjugated) 1,3-cyclohexadiene. Why is this?
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Tags: Birch reduction, energy, eventual product, less stable diene product, Reaction Mechanism, Tutorial material
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December 3rd, 2012
I promised that the follow-up to on the topic of Birch reduction would focus on the proton transfer reaction between the radical anion of anisole and a proton source, as part of analysing whether the mechanistic pathway proceeds O or M.
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Tags: Birch reduction, dielectric, energy, free energy, free energy barrier, Hammonds postulate, proton transfer, Reaction Mechanism, Tutorial material
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December 1st, 2012
The Birch reduction is a classic method for partially reducing e.g. aryl ethers using electrons (from sodium dissolved in ammonia) as the reductant rather than e.g. dihydrogen. As happens occasionally in chemistry, a long debate broke out over the two alternative mechanisms labelled O (for ortho protonation of the initial radical anion intermediate) or M (for meta protonation). Text books seem to have settled down of late in favour of O. Here I take a look at the issue myself.
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Tags: dielectric, energy, free energy, Reaction Mechanism, Tutorial material
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November 30th, 2012
A dichotomy is a division into two mutually exclusive, opposed, or contradictory groups. Consider the reaction below. The bicyclic pentadiene on the left could in principle open on heating to give the monocyclic [12]-annulene (blue or red) via what is called an electrocyclic reaction as either a six (red) or eight (blue) electron process. These two possibilities represent our dichotomy; according to the Woodward-Hoffmann (WH) pericyclic selection rules, they represent contradictory groups. Depending on the (relative) stereochemistry at the ring junctions, if one reaction is allowed by the WH rules, the other must be forbidden, and of course vice-versa. It is a nice challenge to ask students to see if the dichotomy can be reconciled.
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Tags: Möbius, pericyclic, pericylic, positive energy activation barrier, Reaction Mechanism, Tutorial material
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November 26th, 2012
I was intrigued by one aspect of the calculated transition state for di-imide reduction of an alkene; the calculated NMR shieldings indicated an diatropic ring current at the centre of the ring, but very deshielded shifts for the hydrogen atoms being transferred. This indicated, like most thermal pericyclic reactions, an aromatic transition state. Well, one game one can play with this sort of reaction is to add a double bond. This adds quite a twist to this classical reaction!
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Tags: free energy, Möbius knot, Möbius link, pericyclic, Reaction Mechanism
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