Three-component coupling reaction for the synthesis of fully substituted triazoles: reactivity control of Cu-acetylide toward alkyl azides and diazo compounds

Herein, we report a Cu-catalyzed three-component coupling reaction of alkynes, azides, and diazo compounds for the synthesis of fully substituted triazoles. The reactivities of alkyl azides and diazo compounds toward Cu-acetylide were controlled by the introduction of a ligand and the stoichiometry of azide and diazo compounds to suppress the undesired protonation or the alkyne-diazo coupling, maximizing the selectivity for the three-component coupling. Besides, the use of aliphatic alkynes was crucial for achieving high selectivity for the three-component coupling reaction. This method features mild reaction conditions, broad substrate scope, and good functional group tolerance. A variety of fully substituted triazoles and ring-fused triazoles were synthesized by this method in moderate to good yields.

Automated summary

In this study, a copper-catalyzed three-component coupling reaction was reported for the synthesis of fully substituted triazoles. Reactivities of alkyl azides and diazo compounds were controlled to enhance selectivity, particularly by introducing a ligand and adjusting stoichiometry. The use of aliphatic alkynes was crucial for achieving high selectivity and moderate to good yields.