Pretenders

Chemists are well familiar with the concept of umpolung, which describes a deliberate attempt to change the natural polarity of a functional group. Earlier today I was thinking about functional groups that “sneak” into known reactions and behave as if they were molecular components one is used to seeing in a particular process. These are not chameleons, and they are probably not even pretenders per se… But there has got to be a decent way of categorizing these functional groups. And, by the way, the title “pretenders” does not have any negative connotations. If anything, this is a compliment to a group that emerges as a replacement for something that is ingrained in the lore of a particular kind of reactivity. Take azide/alkyne cycloaddition as an example. The power of this process, and the reason it is likely to result in a Nobel Prize one day, is that azide and alkyne are considered to be unique in their orthogonality to almost everything out there, yet react very predictably and cleanly with each other under copper catalysis. Below is a case for a “pretender”, if you will. I refer to the phosphorous ylide molecule. The metal-free process you see allows one to make peptidomimetics containing triazoles as cis-amide bond mimetics. Among several notable features of this reaction, developed by Rademann and colleagues some years ago, is that it bypasses the need to use amino acid alkynes that are not always easy to make. For me, though, the most attractive feature of this chemistry is that identifies a functional group that does something that is “reserved” for another one.