Bidentate ligand promoted palladium-catalyzed C–H olefination of aromatic compounds

Metal-catalyzed C–H functionalization is an attractive strategy to introduce complexity in organic molecules since no pre-functionalization of the starting materials is required. However, the low reactivity of C‒H bonds and the poor selectivity observed in molecules that contain diverse C–H bonds are the main obstacles in the development of efficient C‒H bond transformations. To unlock the full potential of metal-catalyzed C–H functionalization, the discovery of new ligands capable of increasing the reactivity and selectivity of these processes is of central importance. Herein, we described the design, synthesis and evaluation of a new class of bidentate ligands, based on both heteroatom and carboxylic acid functionalities, for C–H functionalization reactions.
In Chapter 2, the development of a new and general methodology for the synthesis of α-substituted phosphinoacetic acids (P,O-ligands) is reported. In Chapters 3–5, the synthesis of new class of ligands in metal catalysis, namely thioethercarboxylic acids (S,O-ligands), is described. The application of these ligands in palladium-catalyzed C–H olefination of simple arenes, including anilines, is presented. The new methodologies proceed efficiently with a broad range of substrates and olefins providing the olefinated product in good yields. We have shown that these methodologies are operationally simple, scalable, and can be used in late-stage functionalization of complex molecules. The S,O-ligand is responsible for the dramatic improvements in substrate scope and the high selectivity observed in these transformations. In Chapter 6, mechanistic studies to understand the role of the S,O-ligand in these reactions are presented.