An unprecedented approach that enables the direct and selective preparation of 1,5-disubstituted 1,2,3-triazoles from abundantly available building blocks such as primary amines, enolizable ketones and 4-nitrophenyl azide as a renewable source of dinitrogen via an organocascade process has been developed. Furthermore, this efficient methodology also enables the synthesis of fully functionalized and fused N-substituted heterocycles.

NH-1,2,3-Triazole moieties are a part of the design of various biologically active compounds, pharmaceutical agents and functional materials. Unfortunately, the applications of this heterocycle are still underexplored due to the lack of a general synthetic protocol. Here we outline a novel, general and facile metal-free pathway that enables the direct synthesis of these heterocycles by combining readily accessible and abundant precursors such as enolizable ketones and NH4OAc with high levels of regioselectivity via an organocascade process. The developed chemistry has been successfully applied to the synthesis of several structurally diverse products, pharmaceutical agents and supramolecular receptors.

This TFA-catalyzed [3+2] cycloaddition of organic azides with α-fluoronitroalkenes, used as synthetic surrogates of α-fluoroalkynes, provides a new route to multi-substituted fluorotriazoles with broader substrate scopes and high regioselectivity.