A late-stage diversification strategy for synthesizing ynamides has been developed. This strategy was enabled by the copper-catalyzed direct electrophilic diynylation of sulfonamides with a novel triisopropylsilyl diynyl benziodoxolone, deprotection, and the late-stage chemoselective copper-catalyzed azide-alkyne cycloaddition sequence, which yields various complex molecule-derived ynamides with pyrene, amino acid, nucleoside, and N-acetylglucosamine as substituents.