Microwave-Assisted Precise Synthesis of Alkyl/Aryl-Modified Triazolyl-Phenylalanine Hybrids and Peptide Modifications through Multicomponent Reaction

We report a regioselective synthesis of triazolyl-phenylalanine hybrids via a two-step process: alkynylation at ambient conditions followed by multicomponent reaction, which includes protodesilylation, azidation, and [3 + 2] cycloaddition under microwave irradiation. This approach eliminates the isolation and purification of reactive intermediates, the handling of potentially explosive azides, and the Glaser homocoupling. Under sustainable conditions, the method supports a broad substrate scope, including pseudopeptides, <i>bis</i>-triazoles, and iterative ditriazole frameworks, and enables the synthesis of triazole-modified peptides.