Integration of SuFEx and Sonogashira Cross-Coupling for the Synthesis of Structurally Diverse Aryl Acetylenes on DNA

To address the current limitations of DNA-compatible Sonogashira cross-coupling reactions capable of accommodating a broad range of commercially available phenolic building blocks (BBs), an <i>in situ</i> SuFEx-Sonogashira cross-coupling protocol has been developed. This protocol involves the conversion of readily accessible phenolic compounds into the corresponding aryl fluorosulfates within 96-well microplates via a highly efficient <i>in situ</i> liquid-phase SuFEx reaction, followed by Sonogashira cross-coupling with DNA-conjugated terminal alkynes.