It’s hard to go wrong with rearrangement chemistry. It’s really the most atom-economical chemistry that one can do, converting one molecule into another without the influence of anything aside from heat, light, and/or solvent. Sam Danishefsky delivers a nice two-for-one in his latest Organic Letters contribution on the reaction of isonitriles with carboxylic acids to generate what one might call “amide anhydrides” (see diagram). S.D. calls them, perhaps more clearly than I, “N-formyl amides.”
Using computational chemistry, Danishefsky rules out polar and radical intermediates for the reaction, demonstrating that two concerted (but not necessarily synchronous) processes must take place. In the first, the electron-rich carboxylic acid group approaches the electrophilic, carbene-esque carbon of the isonitrile. Simultaneously, the isonitrile carbon receives electron density from the carbonyl O and donates it to the acidic proton, which ultimately generates a mixed hydride intermediate…an “imine anhydride,” if you will. Not a rearrangement per se, but 100% atom economical nonetheless.
The second process is a bona fide rearrangement, as the COPh group migrates from oxygen to nitrogen and a second carbonyl (formyl) group forms. Calculations showed both concerted processes to be exothermic in the gas phase and in chloroform, while polar and radical mechanisms proved to have intermediate steps that were ridiculously endothermic. Organic chemistry takes a few torturous steps up the slippery slope that is computational chemistry!