Defying Woodward-Hoffmann with a Yank

As Paul from TotallySynthetic has mentioned, this issue of Nature is packed with organic chemistry- rather unusual for the journal. Reviewed in TotSyn was Baran's protecting group-free total synthesis of Ambiguine H and other molecules, which is quite a read. Also in the issue are papers by Bergman on C-H activation and one on relativistic effects in gold catalysis by demi-god F. Dean Toste. Like I said, jam-packed with organic-y goodness.

Then there's the cover story. This one's particularly near and dear to my heart, as it comes from my own group. The Moore group, in collaboration with profs from materials science and aerospace engineering, has developed a system which displays new reactivity when mechanical energy is utilized. The article has a much more thorough description than I could butcher out, so instead, I'll just attempt to give a general description. (You should read the article anyway.) If you're reading this blog, chances are good that you're at least partially familiar with the Woodward-Hoffmann rules, which predict the geometry of products of pericyclic reactions. The pericyclic reaction in question is the 4-electron concerted ring-opening of 1,2-disubstituted benzocyclobutenes. The Woodward-Hoffmann rules dictate that heating of this system should undergo conrotary ring-opening, and illumination of this system should result in disrotary ring-opening, regardless of the substituents. However, as computational studies have predicted and experiment has confirmed, the ring-opening geometry when mechanical energy is used is dependent on the geometry of the subtituents- in other words, whether conrotary or disrotary ring-opening occurs is dependent on whether the disubstituted benzocyclobutene is cis or trans.

This new reactivity isn't terribly hard to comprehend. You can do this experiment at home, without even having to resort to messy density functional theory like they did. Simply make a model of benzocyclobutene, and attach strings to each sp³ carbon. Now yank on the strings, hard. Whether you attach the strings on the same side (cis) or on different sides (trans), and assuming the model doesn't break (don't yank too hard), you end up with the same product, in stark contrast to the Woodward-Hoffmann rules. It's completely intuitive, again in stark contrast to the Woodward-Hoffmann rules. :)

So, great. It works in theory. The clever bit was proving this happens on a molecular level. The Moore group, being the deft polymer chemists they are (we are? though I don't do polymers), decided to utilize polymer tethers (namely poly(ethylene glycol)) as the "strings." A fluorescent, ¹³C-enriched dienophile was used to "capture" the ring-opening products via Diels-Alder cycloadditions, which were purified and analyzed by GPC and NMR.

The source for the mechanical energy was ultrasound. Pioneered in part by Ken Suslick in the same department, ultrasound is a viable source of mechanical energy on the nanoscale. Ultrasound induces small cavitation bubble formation in liquids which subsequently (and quickly) collapse. The collapse causes liquid molecules to "rush" into the space, resulting in frictional forces against the reactant molecules. (neat, huh?) Using ultrasound as the mechanical energy source, both cis and trans-polymer substituted benzocyclobutenes react to give the same stereoisomer, agreeing with theory. A very clever experiment!

So yes, I am tooting my own horn here, as it's my own group's work, even though I had nothing to do with it. But it is very novel science, indeed (plus, it probably won't happen again that I get to brag about my group making the cover of Nature). Although this system probably doesn't serve any practical purpose, it might open the doors to new systems which utilize mechanical stress as their main energy source. For more info, there are some fun videos on the Nature website with the Bossman explaining the lure of mechanochemistry and the development of the system.