Late-stage diversification strategy for synthesizing ynamides through copper-catalyzed diynylation and azide-alkyne cycloaddition

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.

Automated summary

A late-stage diversification strategy for synthesizing ynamides with various substituents, including pyrene, amino acid, nucleoside, and N-acetylglucosamine, has been developed. This strategy involves 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.