Synthesis of 1,2,3-triazole-fused N-heterocycles from N-alkynyl hydroxyisoindolinones and sodium azide via the Huisgen reaction

Abstract

An efficient methodology for the synthesis of dihydro[1,2,3]triazolo-pyrimidoisoindolones and dihydro[1,2,3]triazolo-diazepinoisoindolones has been developed using the Huisgen reaction from sodium azide and alkyne substituted amido alcohols in moderate to good yields. The reaction involves the in situ generation of the N-acyliminium ion intermediate, which undergoes a nucleophilic attack by the azide ion, followed by a [3 + 2]-intramolecular azide–alkyne cycloaddition reaction. Importantly, the reaction proceeds without the involvement of any transition metal catalyst. This methodology can be further utilized for the synthesis of dihydro[1,2,3]triazolo-pyrimidoisoindolthiones via thionation of amides.