I was intrigued by a recent paper from the Stoltz lab. In it, the authors describe their ongoing efforts to generate and characterize strained amides. For years, Kirby dominated the landscape of unusual amides characterized by the lack of C/N overlap. Then came Stoltz and his imaginative use of the Aubé-Schmidt reaction. This area of research has been a race toward the most strained amide structure. Stoltz’s recent addition to the list of weird amides (see the structure shown below) is the front-runner at this point. Notable spectroscopic features include a C=O IR stretch of 1877 cm-1. The X-ray analysis holds the most interesting result: the ξ angle of 5.8o. The authors propose to use “ξ” to refer to the O-C-N deviation from 120o degrees. For clarity, I am exaggerating the ξ value in my drawing below. The explanation for the deviation offered by Stoltz has to do with the p-like oxygen orbital and its interaction with the C-N σ* orbital. In my view, there is an interesting connection here to the “n-to-π*” interactions popularized by Raines. I talked about it the past and raised a point about the “infamous” rabbit ears (https://amphoteros.com/2015/06/25/rabbit-ears/).
It is a nice educational point that the Kirby/Stoltz twisted amides do not behave like typical amides – they possess basic nitrogen and hydrolyze like crazy. (I remember many years ago, Evans was musing in a lecture whether nature uses this trick, if there is any amide hydrolase enzymes that would destabilize amide “mechanically” by twisting it out of plane. )
Well, this is a good point and nature appears to do something along these lines. Berkessel looked at what later became known as “Olah’s enzyme”: http://www.sciencedirect.com/science/article/pii/S1367593100002453. I have not followed this area for some time, so I cannot comment on what came out of it and whether or not the mechanism was rigorously proven.