B.R.S.M. When all you have is a hammer everything looks like a nail

10Jul/116

Eaton’s other reagents

On Friday, I found myself discussing the use of Eaton's reagent with a coworker. Many people know it as a handy alternative to polyphosphoric acid (PPA) for acylations, Friedel-Crafts reactions and the like. It's even endorsed by Milkshake. A simple 7.7 wt% solution of phosphorus pentoxide in methanesulfonic acid, it's not as viscid, viscous or  unpleasant to work up as PPA.[1] And it's commercially available. But neither my coworker, nor many other people I know, are aware of Eaton's other contributions to the synthetic world. He's still an emeritus professor at the University of Chicago, and you can read about his interests on his website, but what he's most famous for, unbeknownst to many younger chemists, is his synthesis of the cubanes.

My favourite thing about Eaton's seminal JACS paper on cubane is the title,[2] which is simply the word Cubane. I mean, can you imagine what would happen if it'd been synthesised for the first time last week? I think it'd be a little more self aggrandising.

I'll quickly show the synthesis, as the idea of drawing cubes in Chemdraw appeals to me. The route began with the conversion of cyclopentenone to the tribromide shown by radical, followed by ionic bromination. This compound was then treated with diethylamine at low temperature, causing a double E1cB elimination to give the unstable dienone that then dimerises immediately to the tricyclic diketone. Both ketones were then protected as the corresponding dioxolanes, and the a,b-unsaturated one was selectively cleaved using hydrochloric acid to give the a-bromoketone. A solution of this monoprotected compound in benzene was then exposed to UV light, undergoing a [2 + 2] intramolecular cycloaddition in almost quantitative yield. Treatment with aqueous base effected a Favorskii-type ring contraction to give the carboxylic acid. This was then converted via the acid chloride to the t-butyl perester which, when heated in refluxing cumene, underwent radical fragmentation to give a moderate yield of the decarboxylated product. The same five steps were then repeated to give the unnatural product.

A number of improved syntheses exist, some of which appear on this website. Cubane derivatives happen to make awesome explosives, due to their very strained nature and high densities. See the wikipage for octanitrocubane, whose structure is shown above. They're also not that shock sensitive. Apparently. Cubane was thought impossible until Eaton reported it, and although its synthesis was an awesome chemical achievement, the curiosity behind it was perhaps even more admirable. I mean, what does it even do?

I first read about the synthesis of cubane in an article by Roald Hoffmann entitled 'In Praise Of Synthesis' (free from his website!). It's accompanied by a memorable quote from the famous (British) magazine Punch:

you can make anything, from salve to a star,

(if you only know how), from black coal tar.

 

That's organic chemistry for you.

References

1. The original paper is J. Org. Chem., 1973, 38, 4071–4073.

2. Philip E. Eaton and Thomas W. Cole, J. Am. Chem. Soc., 1964, 86, 3157–3158.

 

Comments (6) Trackbacks (0)
  1. Are you omitting the 8th nitrogroup on purpose. Nice Blog, by the way!!!

  2. Nope, that’s definitely an error, although the paper does also describe the heptanitro version. I’ll fix that when I can. Thanks! (for pointing out the error, and for the compliment)

  3. Did you intend to mention the photocyclization of the partially protected dimer? Also, the synthesis started with cyclopentEnone.

  4. Some gossip I heard on cubane is that Eaton got his student/postdoc to do all the steps up to the final one, but Eaton wanted to do the final step himself so he could be the first to make it.

    • I hope that’s true, because it makes a good story. Do you know of any other natural products where the academic in charge of the group jumped in for the last step?


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