Chemoselective sequential "click" ligation using unsymmetrical bisazides

Org Lett. 2012 May 18;14(10):2590-3. doi: 10.1021/ol300899n. Epub 2012 May 4.

Abstract

Unsymmetrical bisazides containing chelating and nonchelating azido groups undergo chemoselective three-component copper(I)-catalyzed azide-alkyne conjugation reactions with two different alkyne molecules. In conjunction with the reactivity gap between aromatic and aliphatic alkynes, a bistriazole molecule can be generated with excellent regioselectivity by mixing two alkynes and a bisazide in a single reaction container. This method is applicable in aqueous solutions at neutral pH, which may lend utilities in bioconjugation applications.