In 2010, Barbas and coworkers developed the use of N4-substituted 1,2,4-triazoline-3,5-diones (TADs) reagents for Tyr-selective protein bioconjugation (Figure ). These aqueous-compatible reactions are described as 'click-like' by virtue of their favorable reaction rates and residue-selectivity. Accordingly, many TAD reagents have been prepared for protein bioconjugation studies, discriminating changes in protein structure, and recent electrochemical oxidation methods have been developed to enable the in situ generation of N4-substituted TAD reagents from their corresponding N4-substituted urazole precursors. The procedural ease of these developments encouraged us to examine scenarios where in situ generated N4-substituted TAD peptides could react with sequence-embedded Tyr residues to produce Tyr-linked cyclic peptides (Figure ). The method design was predicated on several objectives. We sought to (1) provide predictable and modular access to Tyr-linked cyclic peptides, using (2) peptide-compatible oxidation conditions that tolerate native residue functionalities, while (3) being procedurally simple to perform. In this approach, we show N4-substituted urazoles are readily built using N-terminal or embedded amines of Tyr-containing peptides. The urazole moiety can be chemoselectively oxidized in situ to generate a N4-substituted TAD peptide that undergoes spontaneous cyclization with an embedded Tyr residue under aqueous conditions.