Sure, there's your decarboxylations, your ozonolyses, your samarium iodide reductions. Long ago, natural enzymes figured out how to push electron density around to slice up substrates: think about gramine fragmentation, Poitier oxidation, or the (now-defunct) Pictet-Spengler spiro mechanism. But you don't often see fully saturated sp3 carbon-carbon bonds falling apart; after all, we'd be dealing biology a mortal blow with such precarious engineering.
Wouldn't it be cool, though, if we could just add a specific catalyst, a dash of water, and selectively crack a hydrocarbon?
|I don't recall seeing this graphic in the SI...but I can hope.|
Turns out you can...if the system's just right. Chinese University of Hong Kong chemistry professor Kin Shing Chan, with coworkers Ching Tat To and Kwong Shing Choi, reported just such a reaction in JACS ASAP yesterday. The scientists mix some Rh(III) porphyrin, some base, and a 100-fold excess of water, heating everything in the dark for 2-3 days. Out pops the "bibenzyl" compound (83%), which initially causes a bit of head-scratching: why don't they see C-H activation products? And where's the hydrogen coming from?
There's quite a bit of C-H activation, actually - it just doesn't go anywhere under the conditions. Swapping in deuterium oxide leads, unsurprisingly, to "D" incorporation on all the methylene groups and at the two newly-formed methyl groups. So the water indeed provides hydrogen, but not the way we'd usually think about it. No water splitting, no hydride formation, no "M-H." Instead, it's simply a radical quench: each metal-carbon bond, formed from C-C bond homolysis, grabs an "H-dot" from a neighboring water, and the remaining OH radicals shuffle away to produce hydrogen peroxide. And the rate looks pretty screwy, with second-order kinetics in metal, which the authors think means that two separate Rh(II) radical species - from Rh(III) reduction in situ - cooperate to cleave each side of the C-C bond simultaneously.
|Source: Chan et. al., JACS ASAP 2012|
Well, enough hype: only a few substrates (cyclooctane, cyclophane, strained substrates) have been shown to reliably react with these rhodium porphyrins, and the conditions (200 degrees Celsius, 3-4 days, in the dark?!?) aren't winning any immediate med chem converts. Hey, these things take a little time to become practical, so maybe one day you'll reach for your C-C "knife" of choice, and dial-in your molecular dissection.