Treating nitrogen with respect is one of the things I have learned to appreciate over the years. No other element has so much going for it, especially under seemingly trivial conditions and in mundane settings. When Iain Watson was doing his PhD in my lab, he stumbled upon an effect that helped shape our thinking for many years. At that point of time, we had just started looking at the properties of amines in constrained environments. Iain discovered that aziridines displayed some aberrant behaviour in palladium-catalyzed allylic amination reactions. The kinetic branched product never isomerized into the linear one, which was odd considering what had been known prior to our work. We spent several years trying to understand this effect; several generations of my students took those results further and developed some rather nice methods. The irony is that we still have arguments about the origins of allyl aziridine stability against isomerization. But then again, at least the experimentally observed aberration was at the very “start” of the cyclic amine series, allowing us to end any argument with “Oh well, these rings are seriously strained after all… Let’s just go have a beer or something”. You probably know how circular arguments develop and propagate.
http://pubs.acs.org/doi/abs/10.1021/ja049242f
http://www.nature.com/nmeth/journal/v12/n3/full/nmeth.3256.html
Now hold on to your seats. Professor Igor Alabugin of Florida State University sent me a really nice book chapter he has been writing. In it, he elaborates on the s-character trends in the secondary amine series and cites a paper that made me scratch my head. This 2014 Nature Methods piece prescribes the use of azetidines (four-membered heterocycles with one nitrogen) in order to dramatically boost the quantum yield of certain fluorescent dyes. The three- and five-membered congeners are both inferior in this application, whereas the four-membered one hits the sweet spot.
Planting outliers in a series where one might naively expect some cute little trend is where organic chemistry is at its finest. The rationale behind the azetidine effect is most likely rather complicated. That’s ok: incorporating azetidines into dyes is now billed as a general method to improve fluorophores for live-cell microscopy. Way to go, azetidines…