Click Chemistry for the Synthesis of Azides

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.