In a previous post on the topic, I remarked how the regiospecific ethanolysis of propene epoxide 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[ 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.
Posts Tagged ‘free energy’
The mechanism of ester hydrolysis is a staple of examination questions in organic chemistry. To get a good grade, one might have to reproduce something like the below. Here, I subject that answer to a reality check.
I mentioned in the last post that one can try to predict the outcome of electrophilic aromatic substitution by approximating the properties of the transition state from those of either the reactant or the (presumed Wheland) intermediate by invoking Hammond’s postulate. A third option is readily available nowadays; calculate the transition state directly. Here are the results of exploring this third variation.
- G.S. Hammond, "A Correlation of Reaction Rates", J. Am. Chem. Soc., vol. 77, pp. 334-338, 1955. http://dx.doi.org/10.1021/ja01607a027
Consider acetaldehyde (ethanal for progressive nomenclaturists). What conformation does it adopt, and why? This question was posed of me by a student at the end of a recent lecture of mine. Surely, an easy answer to give? Read on …
I return to this reaction one more time. Trying to explain why it is enantioselective for the epoxide product poses peculiar difficulties. Most of the substituents can adopt one of several conformations, and some exploration of this conformational space is needed.
I have written earlier about dihydrocostunolide, and how in 1963 Corey missed spotting the electronic origins of a key step in its synthesis.. 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.
- E.J. Corey, and A.G. Hortmann, "The Total Synthesis of Dihydrocostunolide", J. Am. Chem. Soc., vol. 87, pp. 5736-5742, 1965. http://dx.doi.org/10.1021/ja00952a037
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", J. Org. Chem., 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", J. Org. Chem., vol. 51, pp. 1922-1925, 1986. http://dx.doi.org/10.1021/jo00360a058
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.
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.