About a year and a half ago, I was asked to put together a special issue of Chemical Reviews dedicated to small ring heterocycles. This project has taken a lot of organizational effort, but it has been rewarding to assemble a team of researchers who have pushed back the frontiers of this area over the past 10-15 years. I am going to post more information pertaining to this special issue as the project nears completion, so stay tuned. I just want to mention one name from this compilation: Professor Daniel Romo of Texas A & M University. The reason I want to talk about some of his classic work tonight is because it serves as an example of going after molecules which, on paper, have little reason to exist, yet are surprisingly stable even to column chromatography. Below you see Romo’s spiroepoxy-beta-lactones. Their synthesis is deceptively simple: add DMDO to a diketene. That’s it. The resulting molecules look wild, but many of them are isolable and stable to column chromatography. In these structures, you might imagine some really interesting manifestations of the anomeric effect. Romo talks about the crystal structure of a representative member of this series in his JACS report and discusses stereoelectronics there. There are also some nice synthetic applications of spiroepoxy-beta-lactones demonstrated in this manuscript. One disadvantage of these molecules is the symmetry of the ketene dimer precursors. Oh well, life can’t be perfect (my lab knows it all too well when we deal with an occasional reaction that does not fully destroy the aziridine aldehyde dimer).
amphoteros 
to me, the most monstrous molecule is 1,5-cyclooctadiyne: two bent triple bonds that are part of an 8-membered ring. That thing is isolable and stable enough at room temperature that some interesting cyclization chemistry and also double copper-free click reactions were done with it
I agree! This is a good one…