S,O-ligand-promoted palladium-catalyzed C–H functionalization of anisole and aniline derivatives

The present PhD thesis deals with the exciting and rapidly evolving field of non-directed C−H functionalization, a groundbreaking approach revolutionizing modern organic synthesis. Traditional synthetic chemistry has heavily relied on prefunctionalization strategies, impeding synthetic efficiency and atom economy. Direct C−H functionalization offers a transformative method for forming C−C and C−X bonds directly from nonfunctionalized substrates, overcoming limitations posed by prefunctionalization. However, challenges such as low reactivity of C−H bonds and selectivity issues persist. The thesis comprises several chapters focusing on the development of synthetic methodologies to achieve precise control over the site-selectivity of C−H functionalization reactions in anisole and aniline derivatives. The catalytic activity of the Pd/S,O-ligand catalyst, particularly in combination with norbornene mediators, is explored. In Chapter 2, a methodology for C−H olefination of anisole derivatives is detailed, emphasizing the importance of ligand modification and solvent selection. Chapter 3 introduces a catalytic system for meta-C−H arylation of aryl ethers, demonstrating superior performance compared to existing systems. Chapter 4 presents the first general and efficient meta-C−H arylation of non-directed aniline derivatives via cooperative catalysis with a palladium–S,O-ligand–norbornene system. Chapter 5 optimizes meta-C−H methylation of non-directed aromatic amines, expanding the scope of late-stage methylation methodologies. Chapter 6 investigates the role of silver salts in Pd/S,O-ligand/NBE catalyzed meta-C−H arylation, providing insights into the kinetics and revealing silver's dual function as a halide scavenger and a promoter of oxidative addition. The thesis contributes significantly to advancing non-directed C−H functionalization, offering new synthetic strategies with broad applications in organic synthesis.