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 CO2H). Compound 1 itself nowadays is used to calibrate chiroptical calculations[cite]10.1021/ct300359s[/cite], which is what brought it to my attention. But about four decades ago, and now largely forgotten, both 1 and the dicarboxylic acid were famous for the following rearrangement that gives a mixture of 2 and 3[cite]10.1021/ja00747a019[/cite]. I thought I might here unpick some of the wonderfully subtle stereochemical analysis that this little molecule became subjected to.
Posts Tagged ‘Reaction Mechanism’
Feist’s acid. Stereochemistry galore.
Thursday, April 4th, 2013The mechanism of ester hydrolysis via alkyl oxygen cleavage under a quantum microscope
Tuesday, April 2nd, 2013A sideways look at the mechanism of ester hydrolysis.
Friday, March 29th, 2013The 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.
Concerted vs stepwise (Meisenheimer) mechanisms for aromatic nucleophilic substitution.
Monday, March 25th, 2013My 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; are there any circumstances under which the mechanism could instead be concerted, by-passing this intermediate?
Kinetic vs Thermodynamic control. Subversive thoughts for electrophilic substitution of Indole.
Sunday, March 10th, 2013I 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.
Understanding the electrophilic aromatic substitution of indole.
Sunday, March 3rd, 2013The electrophilic substitution of indoles is a staple of any course on organic chemistry. Indoles also hold a soft-spot for me, since I synthesized not a few as part of my Ph.D. studies.[cite]10.1039/P29750001209[/cite],[cite]10.1039/P29770000281[/cite] The preference for substitution in the 3-position is normally explained using the arrows shown below (position 3=green,2=blue,1=red). Here I explore how these arrows might be interpreted in terms of various quantum mechanical properties.
The π-complex in the benzidine rearrangement: a molecular orbital analysis.
Friday, January 18th, 2013Michael 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.
The Benzidine rearrangement. Computed kinetic isotope effects.
Friday, January 11th, 2013Kinetic 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 bisprotonation of diphenyl hydrazine, but what happens next was the crux. Does this species rearrange directly to the C-C coupled intermediate (a concerted [5,5] sigmatropic reaction) or does it instead form a π-complex, as famously first suggested by Michael Dewar[cite]10.1016/S0040-4039(01)82765-9[/cite] [via TS(NN] and only then in a second step [via TS(CC)] form the C-C bond? Here I explore the isotope effects measured and calculated for this exact system.