Unlocking palladium catalysis S,O-ligand-promoted C-H functionalization of arenes

Over the past decades, palladium-catalyzed (Pd-catalyzed) C–H activation has revolutionized the formation of C–C and C–X bonds, offering atom- and step-economic transformations without the need of pre-functionalization. Recently, non-directed C–H activation has gained increasing attention as a straightforward approach, driven by the development of diverse ligands. This thesis focuses on advancing non-directed C–H functionalization using arene as the limiting reagent through innovative Pd/S,O-ligand catalytic systems, delivering efficient and industrially relevant methodologies.
More specifically, a para-selective Pd-catalyzed C–H alkynylation of anilines enabled by the S,O-ligand is presented in Chapter 2. This method achieves good yields with a broad substrate scope, showcasing its potential for downstream synthetic applications.
A versatile C–H arylation reaction for anisole derivatives using aryl iodides under mild conditions is presented in Chapter 3. This methodology achieves arylation with excellent efficiency and selectivity, accommodating diverse substrates and enabling late-stage functionalization of bioactive molecules.
Chapter 4 describes a Pd/S,O-ligand catalyzed oxidative dehydrogenative homocoupling of arenes, employing O₂ as the sole oxidant at room temperature. This transformation affords biaryl dimers with high regioselectivity. Its application to the synthesis of a key precursor of the Upilex® monomer demonstrates the industrial relevance of the methodology.
By expanding the utility of Pd/S,O-ligand catalysis, these studies establish a foundation for more sustainable and versatile C–H functionalization reactions, driving innovation in the synthesis of pharmaceuticals, functional materials, and beyond.