Direct organocatalytic chemoselective synthesis of pharmaceutically active benzothiazole/benzoxazole-triazoles†

Abstract

Benzothiazole and benzoxazole heterocyclic ring-containing 1,4,5-trisubstituted-1,2,3-triazoles are well known for their wide range of applications in pharmaceutical and medicinal chemistry, but their high-yielding metal-free selective synthesis has always remained challenging as no comprehensive simple protocol has been outlined to date. Owing to their structural and medicinal importance, herein, we synthesized various benzothiazole and benzoxazole heterocyclic ring-containing 1,4,5-trisubstituted-1,2,3-triazoles in high to excellent yields with chemo-/regioselectivity from the library of benzothiazole/benzoxazole-ketones and aryl/alkyl-azides through an enolate-mediated organocatalytic azide-ketone [3 + 2]-cycloaddition under ambient conditions in a few hours. The commercial availability or quick synthesis of the starting materials and catalysts, a diverse substrate scope, chemo-/regioselectivity, quick synthesis of pharmaceutically active known compounds and their analogues, and numerous medicinal applications of functionalized benzothiazole/benzoxazole-triazoles are the key attractions of this metal-free organo-click reaction.