Sharpless epoxidation converts a prochiral allylic alcohol into the corresponding chiral epoxide with > 90% enantiomeric excess[cite]10.1021/jo00369a032[/cite],[cite]10.1021/jo00360a058[/cite]. Here is the first step in trying to explain how this magic is achieved.
Archive for the ‘Interesting chemistry’ Category
Why is the Sharpless epoxidation enantioselective? Part 1: a simple model.
Sunday, December 9th, 2012Di-imide reduction with a twist: A Möbius version.
Monday, November 26th, 2012I 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!
The “unexpected” mechanism of peroxide decomposition.
Sunday, November 18th, 2012A game chemists often play is to guess the mechanism for any given reaction. I thought I would give it a go for the decomposition of the tris-peroxide shown below. This reaction is known to (rapidly, very rapidly) result in the production of three molecules of propanone, one of ozone and a lot of entropy (but not heat).[cite]10.1021/ja0464903[/cite]
Thalidomide. The role of water in the mechanism of its aqueous racemisation.
Saturday, November 10th, 2012Thalidomide is a chiral molecule, which was sold in the 1960s as a sedative in its (S,R)-racemic form. The tragedy was that the (S)-isomer was tetragenic, and only the (R) enantiomer acts as a sedative. What was not appreciated at the time is that interconversion of the (S)- and (R) forms takes place quite quickly in aqueous media. Nowadays, quantum modelling can provide good in-silico estimates of the (free) energy barriers for such processes, which in this case is a simple keto-enol tautomerism. In a recently published article[cite]10.1002/chem.201202651[/cite], just such a simulation is reported. By involving two explicit water molecules in the transition state, an (~enthalpic) barrier of 27.7 kcal/mol was obtained. The simulation was conducted just with two water molecules acting as solvent, and without any additional continuum solvation applied. So I thought I would re-evaluate this result by computing it at the ωB97XD/6-311G(d,p)/SCRF=water level (a triple-ζ basis set rather than the double-ζ used before[cite]10.1002/chem.201202651[/cite]), and employing a dispersion-corrected DFT method rather than B3LYP. 
Mechanisms of carbon monoxide insertion reactions: A reality check on carbonylation of methyl manganese pentacarbonyl
Sunday, November 4th, 2012When methyl manganese pentacarbonyl is treated with carbon monoxide in e.g. di-n-butyl ether, acetyl manganese pentacarbonyl is formed. This classic experiment conducted by Cotton (of quadruple bond fame) and Calderazzo in 1962[cite]10.1021/ic50001a008[/cite] dates from an era when chemists conducted extensive kinetic analyses to back up any mechanistic speculations. Their suggested transition state is outlined below. Here I subject their speculations to a quantum mechanical “reality check“.
Secrets of a university tutor. An exercise in mechanistic logic: first dénouement.
Sunday, October 28th, 2012The reaction described in the previous post (below) is an unusual example of nucleophilic attack at an sp2-carbon centre, reportedly resulting in inversion of configuration[cite]10.1021/ja00765a062[/cite]. One can break it down to a sequence of up to eight individual steps, which makes teaching it far easier. But how real is that sequence?
Text-books and the bromination of ethene.
Sunday, October 14th, 2012There is often a disconnect between how a text-book (schematically) represents a reaction and a more quantitive “reality” revealed by quantum mechanics. Is the bromination of ethene to give 1,2-dibromoethane one such example?
Alkyne metathesis: a comparison with alkene metathesis.
Monday, October 8th, 2012Metathesis 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).