Development of On‐DNA Thiophene Synthesis for DEL Construction

Thiophene and its substituted derivatives are a highly important class of heterocyclic compounds, with noteworthy applications in pharmaceutical ingredients. In this study, we leverage the unique reactivity of alkynes to generate thiophenes on‐DNA, using a cascade iodination, Cadiot‐Chodkiewicz coupling and heterocyclization. This approach, tackling on‐DNA thiophene synthesis for the first time, generates diverse, and unprecedented structural and chemical features, which could be significant motifs in DEL screening as molecular recognition agents for drug discovery. We developed a cascade of transformation composed of iodination, Cadiot‐Chodkiewicz coupling and heterocyclization to access pharmaceutically relevant thiophenes, which could be significant motifs in DEL screening as molecular recognition agents for drug discovery.