Back in the days (1893) when few compounds were known, new ones could end up being named after the discoverer. Thus Feist is known for the compound bearing his name; the 2,3 carboxylic acid of methylenecyclopropane ( 1 , with Me replaced by CO ₂ H). Compound 1 itself nowadays is used to calibrate chiroptical calculations[cite]10.1021/ct300359s[/cite], which is what brought it to my attention.

My previous dissection of the mechanism for ester hydrolysis dealt with the acyl-oxygen cleavage route (red bond). There is a much rarer[cite]10.1039/jr9550001522[/cite] alternative: alkyl-oxygen cleavage (green bond) which I now place under the microscope.

My two previous explorations of aromatic substitutions have involved an electrophile (NO ⁺ or Li ⁺ ). Time now to look at a nucleophile, representing nucleophilic aromatic substitution . The mechanism of this is thought to pass through an intermediate analogous to the Wheland for an electrophile, this time known as the Meisenheimer complex[cite]10.1002/jlac.19023230205[/cite]. I ask the same question as before;

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[cite]10.1021/ja01607a027[/cite]. A third option is readily available nowadays; calculate the transition state directly. Here are the results of exploring this third variation.

Michael Dewar[cite]10.1016/S0040-4039(01)82765-9[/cite] famously implicated a so-called π-complex in the benzidine rearrangement, back in the days when quantum mechanical calculations could not yet provide a quantitatively accurate reality check. Because this π-complex actually remains a relatively unusual species to encounter in day-to-day chemistry, I thought I would try to show in a simple way how it forms.

Kinetic isotope effects have become something of a lost art when it comes to exploring reaction mechanisms. But in their heyday they were absolutely critical for establishing the mechanism of the benzidine rearrangement[cite]10.1021/ja00373a028[/cite]. This classic mechanism proceeds via bis protonation of diphenyl hydrazine, but what happens next was the crux.

This is an interesting result I got when studying the [1,4] sigmatropic rearrangement of heptamethylbicyclo-[3.1.0]hexenyl cations. It fits into the last lecture of a series on pericyclic mechanisms, and just before the first lecture on conformational analysis. This is how they join.

Eagle-eyed footnote readers might have spotted one at the bottom of the post on the benzidine rearrangement.

I have written earlier about dihydrocostunolide, and how in 1963 Corey missed spotting the electronic origins of a key step in its synthesis.[cite]10.1021/ja00952a037[/cite]. 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.

I noted briefly in discussing why Birch reduction of benzene gives 1,4-cyclohexadiene (diagram below) that the geometry of the end-stage pentadienyl anion was distorted in the presence of the sodium cation to favour this product. This distortion actually has some pedagogic value, and so I elaborate this here.