Science Express just released an intriguing read from the Fokin group, which uses reaction calorimetry (how hot? how fast?) and mass spec isotopic enrichment studies (where'd that atom come from?) to study the copper-catalyzed click. Using calorimetry, Fokin's group determines that two copper atoms must cooperate to form the desired triazole; the uncatalyzed reaction limps along (~7%) in the same amount of time that the catalyzed reaction - which gives off a brief burst of heat - reaches completion (>96%).
To try and tease out which copper does what, the team synthesized an isotopically-enriched 63Cu catalyst, which they added to a "normal" (63Cu / 65Cu) isotope blend of a copper-bound acetylide. Time-of-flight mass spec showed isotopic enrichment of copper in the resulting isolated copper species. How the heck can that happen?!?
Well, it can't. . . unless, of course, there's an intermediate where the two copper atoms interchange. Enter the crazy, wild world of gem-dimetalation, a concept several groups (Fürstner, Blum, Gagné) have recently studied for a variety of d10 metals (Pd, Ag, Au). Even more crazy, the enrichment indicates that an NHC ligand "jumps" between the two copper atoms, hardly usual behavior for such a strong donor ligand. To explain these results, Fokin constructs a modified catalytic cycle, shown below:
|Source: Science | Fokin group, Scripps|
Check out that prism-shaped intermediate in the lower left. Anything seem strange about it?
Think, for a moment, about axial chirality. What comes to mind? BINAP, certainly, or the M and P descriptors for allene (cumulated double bonds) chemistry. Well, unless I'm missing something, this intermediate may be the first representation of olefinic axial chirality I've seen. To invoke this intermediate, the alkene in question must really be something special, since the azide has to be disposed roughly 90 degrees out-of-plane!
Usually, alkenes like to sit in sp2 -hybridized space - flat, like a sheet of paper. Rotational energy barriers exist to interchange E to Z olefins, but they usually need lots of energy (heat, light) or a charged intermediate. Here, we have an almost-room-temp, neutral, 3D alkene intermediate: a rare duck indeed.