I wanted to mention this paper that’s out in Nature, especially since I was mentioning azide/alkyne click chemistry the other day. If you’re using that system in any sort of chemical diversity sense, you’ve run into problems on the azide end. There are not a whole lot of commercially available azides out there (although definitely more than there used to be before this reaction became popular!) And while there are ways to prepare them from amines, none of them are wildly appealing. For a while there was an imidazolium reagent that looked promising, but it has some stability problems. Then there’s triflyl azide, but no one enjoys that stuff, either: you have to make it fresh and keep it dilute, and it’s a rather slow reaction that doesn’t always complete.
The current paper, from the Shanghai Inst. for Organic Chemistry and Barry Sharpless at Scripps, describes the use of fluorosulfonylazide, which is generated in solution in situ, as a fast and high-yielding reagent for azide formation from primary amines. The paper describes its use on a very wide variety of structures, with all sorts of complex functional groups, and indeed extends it to 96-well plate format for generating azide libraries. They prepared 1224 azides, half of which are previously unknown in the literature, and show that they’re ready for Cu-catalyzed click chemistry after sitting for at least six months in solution, in the plate wells.
So this looks like first a good way to make specific azides for chemical biology applications, including direct azide formation on very complex substrates and secondly an entry into azide diversity sets, which have really never existed at this scale. Given the number of primary amines out there, though, they sure can now. . .