Meng G,
Guo T,
Ma T,
Zhang J,
Shen Y,
Sharpless KB.
*
Dong J.
* Shanghai Institute of Organic Chemistry, P. R. of China
Modular Click Chemistry Libraries for Functional Screens using a Diazotizing Reagent.
Nature 2019;
574: 86-89
Key words
diazo transfer - click chemistry - azides - chemical library
Significance
Copper-catalyzed azide alkyne click chemistry (CuAAC) is a powerful bioorthogonal reaction that provides triazole products in very high yields. A significant limitation is the restricted access to the azide precursors because azide preparation with NaN3 or TfN3 suffers from long reaction times, toxicity, or risk of explosion. The authors present a new, highly reactive diazo transfer reagent that enables rapid and safe access to azides from amines.
Comment
Previously reported fluorosulfuryl imidazolium triflate salt (Guo et al. Angew. Chem. Int. Ed. 2018, 57, 2605) was treated with NaN3 to generate fluorosulfuryl azide 1 in situ. In an optimized solvent system (DMF–MTBE–H2O), 1 undergoes diazo transfer to a broad variety of amines in a click chemistry fashion.
