Palladium‐Catalyzed Site‐Selective C─H Alkoxylation Using Biorelevant Heterocyclic Directing Groups

This study introduces a novel palladium‐catalyzed alkoxylation method via C─H activation, utilizing an intrinsic, weakly coordinating directing group (DG) derived from bioactive molecules. This approach is particularly relevant for the pharmaceutical and chemical industries, offering a versatile tool for functionalizing complex compounds. The success and site selectivity of this method are determined by the choice of catalytic systems and reaction conditions, including the catalyst, ligand, solvent, and temperature. The substrate scope demonstrates broad applicability, particularly for modifying bioactive scaffolds, highlighting the method's generalizability. This protocol provides a promising route for altering pharmaceutical compounds and other critical chemical products with exceptional regioselectivity. The discovery of an intrinsic DG, combined with the ability to fine‐tune reaction conditions, positions this methodology as a significant advancement for functionalization processes in pharmaceutical and chemical applications, paving the way for further exploration in these fields. A novel palladium‐catalyzed alkoxylation via C─H activation, utilizing an intrinsic weakly coordinating directing group derived from bioactive molecules, is presented. The method offers exceptional regioselectivity and broad applicability for pharmaceutical and chemical industries, enabling functionalization of complex compounds. This approach highlights advancements in substrate scope, reaction tuning, and bioactive scaffold modifications.