Electrochemically driven azide–alkyne cycloaddition (E-CuAAC) via anodic oxidation using dual copper electrodes

Abstract

In recent years, click chemistry has played a pivotal role in diversifying novel heterocyclic compounds to enhance bioavailability. Achieving this diversification via a sustainable electrochemical method is a great challenge and more demanding than it appears. Herein, we report an anodic oxidation-initiated Azide–Alkyne cycloaddition (E-CuAAC) protocol for the synthesis of functionally diverse and biologically significant 1,4-disubstituted-1,2,3-triazoles, demonstrating its potential for sustainable, precise chemical transformations. This methodology leverages electrochemically assisted anodic copper oxidation to facilitate cycloaddition reactions between terminal alkynes and benzyl/aryl azides, employing undivided Cu∥Cu electrodes and NaAsc, which serves as both electrolyte and reducing agent conducted in DMF at +0.6 V under ambient conditions, the protocol achieves excellent yields (95–99%) with a shorter reaction time (30–50 min). The key features include in situ azide generation from bromides, scalable synthesis, and environmentally benign techniques consistent with green chemistry principles. The green metrics of the present protocol demonstrate improved sustainability compared with reported methods, as evidenced by a significantly lower E-factor (0.001–0.456) and higher AEf, CE, RME, EMY, and OE values, confirming its environmentally benign profile. Notably, the apparent faradaic efficiencies ranging from ≈406% (n = 1) to ≈812% (n = 2) reveal a redox-coupled electrocatalytic mechanism, in which the electrode acts as a trigger and sodium ascorbate sustains catalytic turnover, thereby amplifying overall efficiency. The operational simplicity, excellent yield, broad substrate tolerance, gram-scale synthesis, and alignment with eco-friendly methodologies establish it as a significant advancement in electrochemical click chemistry.