8-Hydroxyquinoline catalysed regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles: realizing Cu-free click chemistry

Abstract

Despite numerous reports on the Cu-catalysed click reaction and faster rates of reaction using such catalysts, the pharmacological application of this important synthetic method has become limited and hence advancement towards metal-free click chemistry has increasingly grabbed attention in recent years. Herein we report a regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles via a one-pot azide-alkyne cycloaddition reaction under metal-free conditions using the 8-hydroxyquinoline (8-HQ) catalyst. Along with a plethora of simple triazole derivatives, the protocol has been successfully applied to the synthesis of some bioactive compounds incorporating triazole motifs. Thorough control experiments including deuterium-labelling studies support the proposed mechanism for the reaction wherein the catalyst works as both a proton-abstractor and proton-donor synergistically.