Part I. Palladium-Catalyzed Alkyl Carbon-Hydrogen Activation. Part II. Palladium-Catalyzed Aryl Carbon-Hydrogen Activation

The work in this dissertation is divided into two major parts. Part I describes the Pd-catalyzed activation/functionalization of inert alkyl C(sp3)–H bonds through the development of highly reactive directing groups and identification of compatible ligands that cooperatively promote C(sp3)–H functionalization. Prior to this dissertation research, methods to selectively functionalize methyl and methylene C(sp 3)–H bonds at the β-position of carbonyl groups were underdeveloped. Inspired by the indispensable roles of electronically and sterically optimized phosphine (PR3) and N-heterocyclic carbene (NHC) ligands in traditional cross-coupling reactions, we have invented a class of highly optimized N-arylamide directing groups that weakly coordinate to Pd, yet promote cleavage of β -C(sp3)–H bonds and facilitate subsequent conversion into an array of C–C and C–heteroatom bonds. A unique feature of Pd-catalyzed C(sp3)–H activation reactions using N-arylamide directing groups is that a range of coordinating moieties that are known to compete for the coordination sites around Pd (e.g., PR3, NHC, pyridine, CO, acrylates, and DMF) can be accommodated, while maintaining robust C(sp 3)–H activation. By exploiting the N-arylamide directing group, we have developed the following unprecedented transformations, which will be summarized in five discrete chapters: 1. Pd(0)/PR3-catalyzed intermolecular arylation of β-C(sp3)–H bonds. 2. Pd(II)-catalyzed olefination of β -C(sp3)–H bonds. 3. Pd(II)-catalyzed carbonylation of β-C(sp3)–H bonds. 4. Pd(II)/amino acid-catalyzed enantioselective activation of cyclopropyl C–H bonds. 5. Pd(II)/quinoline-catalyzed arylation of β-methylene C(sp3)–H Bonds.;Part II of this dissertation addresses applications of this same class of amide directing groups for C(sp2)–H activation reactions in developing previously unprecedented C(sp2)–H functionalization reactions. In particular, we have focused our efforts on the following two topics: 1. Pd(II)-catalyzed synthesis of lactams via intramolecular C(sp 2)–H amination. 2. Pd(0)/PR3-catalyzed N- arylamide-directed regioselective C–H arylation of pyridines.;The versatility and practicality of these reactions in their current forms are evaluated with respect to the efficiency of catalysis and substrate scopes. Key problems and potential solutions are also discussed.