Posts Tagged ‘animation’
A tutorial problem in stereoelectronic control. A Grob alternative to the Tiffeneau-Demjanov rearrangement?Saturday, November 28th, 2015
In answering tutorial problems, students often need skills in deciding how much time to spend on explaining what does not happen, as well as what does. Here I explore alternatives to the mechanism outlined in the previous post to see what computation has to say about what does (or might) not happen.
A tutorial problem in stereoelectronic control. The Tiffeneau-Demjanov rearrangement as part of a prostaglandin synthesis.Monday, November 23rd, 2015
This reaction emerged a few years ago (thanks Alan!) as a tutorial problem in organic chemistry, in which students had to devise a mechanism for the reaction and use this to predict the stereochemical outcome at the two chiral centres indicated with *. It originates in a brief report from R. B. Woodward’s group in 1973 describing a prostaglandin synthesis, the stereochemical outcome being crucial. Here I take a look at this mechanism using computation.
- R.B. Woodward, J. Gosteli, I. Ernest, R.J. Friary, G. Nestler, H. Raman, R. Sitrin, C. Suter, and J.K. Whitesell, "Novel synthesis of prostaglandin F2.alpha.", Journal of the American Chemical Society, vol. 95, pp. 6853-6855, 1973. http://dx.doi.org/10.1021/ja00801a066
The outcome of pericyclic reactions con depend most simply on three conditions, any two of which determine the third. Whether the catalyst is Δ or hν (heat or light), the topology determining any stereochemistry and the participating electron count (4n+2/4n). It is always neat to conjure up a simple switch to toggle these; heat or light is simple, but what are the options for toggling the electron count? Here is one I have contrived by playing a game with the periodic table. The ring closure of a divinylketone is called the Nazarov reaction, it being promoted thermodynamically by coordination of a Lewis acid to atom X. Divinyl ketone can be regarded as a hidden pentadienyl cation, since the C=O bond is polarised Cδ+Oδ- in the time-honoured manner of organic chemistry. In this (formal) resonance form, it becomes part of a pentadienyl cation and can electrocyclise via a 4-electron reaction involving a stereochemical process known as conrotation. The new bond is formed antarafacially (from opposite faces) at the termini of the pentadienyl cation (ωB97XD/6-311G(d,p)/SCRF=dichloromethane.). Note that for the uncatalysed reaction, the barrier is high and the reaction is endothermic but adding a BF3 to the oxygen lowers the barrier and removes the endothermicity. So, one can play a game and ask what would happen if the polarity of the C=X bond were to be reversed. This means going left of oxygen in the periodic table, ending at Be. The reaction has a high barrier, but it is strongly exothermic.† However the most noteworthy aspect is that the stereochemistry of the electrocyclisation is now disrotatory, with suprafacial bond formation (from the bottom face in the animation below). The stereochemical outcome of this reaction has been flipped by reversing the polarity of the CX bond.‡ This little example shows how a thought game played using the periodic table can then be reality tested by solving appropriate quantum mechanical equations. In this instance, one is not going to rush into the laboratory to try to replicate the experiment, but it might help catalyse new thoughts amongst the readers of this blog.
- Henry S. Rzepa., "Gaussian Job Archive for C5H6O", 2014. http://dx.doi.org/10.6084/m9.figshare.1125721
- Henry S. Rzepa., "Gaussian Job Archive for C5H6BF3O", 2014. http://dx.doi.org/10.6084/m9.figshare.1125724
- Henry S. Rzepa., "Gaussian Job Archive for C5H6Be", 2014. http://dx.doi.org/10.6084/m9.figshare.1125792
Sharpless epoxidation converts a prochiral allylic alcohol into the corresponding chiral epoxide with > 90% enantiomeric excess,. Here is the first step in trying to explain how this magic is achieved.
- 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. http://dx.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. http://dx.doi.org/10.1021/jo00360a058
In this earlier post, I described how the stereochemistry of π2+π2 cycloadditions occurs suprafacially if induced by light, and how one antarafacial component appears if the reaction is induced by heat alone. I also noted how Woodward and Hoffmann (WH) explained that violations to their rules were avoided by mandating a change in mechanism requiring stepwise pathways with intermediates along the route. Here I illustrate how the stereochemistry of a thermal π2+π2 cycloaddition can indeed avoid an antarafacial component by performing appropriate gymnastic contortions instead of a mechanistic change (a WH violation certainly in the letter of their law, if not their spirit).
In the previous post, I wrote about the processes that might be involved in a molecular wheel rotating. A nano car has four wheels, and surely the most amazing thing is how the wheels manage to move in synchrony. This is one hell of a tough problem, and I do not attempt an answer here, but simply record an odd observation.