Development of on-DNA Formation of Benzofuran for DNA-Encoded Library Synthesis

Using a novel homologation–heterocyclization cascade, the on-DNA synthesis of benzofurans from aldehydes has been developed. The methodology, based on an innovative use of the Seyferth–Gilbert homologation, followed by a high yielding Sonogashira coupling in situ intramolecular cyclization one-pot, two-step reaction, provides a powerful and unique pathway for DNA-encoded library (DEL) synthesis of a wide array of pharmaceutically relevant benzofuran-based scaffolds.