Cascade Azide–Alkyne Cycloaddition/Azetidine Ring-Opening Reactions for Accessing Aminomethyl-Functionalized 1,2,3-Triazole-Fused Bicyclic Heterocycles

This study presents an efficient transition-metal-free method for the synthesis of aminomethyl-decorated 1,2,3-triazole-fused bicyclic heterocycles via a tandem azide-alkyne cycloaddition and azetidine ring-opening reaction. The tandem process proceeds with broad functional group compatibility and high atom economy. Mechanistic studies indicate that the transformation involves an initial [3 + 2] cycloaddition followed by intramolecular triazole-mediated azetidine ring opening. The resulting aminomethyl motif provides a versatile handle for further functionalization, enabling the synthesis of structurally complex, biologically relevant heterocycles including bioactive conjugates.