The selective oxidation of C-H bonds in (hetero)aromatics provides an efficient access to functionalized aromatic molecules of industrial interest. Aerobic oxygen is an ideal terminal oxidants for this transformation because it is readily available and often produces water as the sole byproduct. Homogeneous palladium catalysts are eminently compatible with aerobic turnovers and have seen success in numerous aerobic oxidation processes (e. g., alkene oxidation, alcohol oxidation). In contrast, palladium-catalyzed aerobic oxidative C-H functionalization has been rather underdeveloped. Challenges include slow catalytic turnover, catalyst decomposition and lack of selectivity control (e.g., site selectivity, homo- vs. cross-coupling selectivity). This thesis presents three research projects with different approaches to tackle the unsolved problems in the reaction class of palladium-catalyzed aerobic C-H oxidation of (hetero)aromatics. The reaction mechanism of C-H/C-H coupling of [o]-xylene was characterized, which disclosed a novel, bimetallic pathway. Built on this work, the effect of copper cocatalyst in this reaction was investigated, which revealed a non-traditional role of copper salt in oxidative palladium catalysis and led to the discovery of an improved catalyst system. Last, a synthetic methodology for aerobic indole C-H arylation with ligand-controlled site selectivity was developed, which provided efficient access to pharmaceutically-relevant aryl indoles and led to preliminary mechanistic insights into regiocontrol.

The field of organometallic chemistry has emerged over the last twenty-five years or so to become one of the most important areas of chemistry, and there are no signs of abatement in the intense current interest in the subject, particularly in terms of its proven and potential application in catalytic reactions involving hydrocarbons. The development of the organometallic/ catalysis area has resulted in no small way from many contributions from researchers investigating palladium systems. Even to the well-initiated, there seems a bewildering and diverse variety of organic reactions that are promoted by palladium(II) salts and complexes. Such homogeneous reactions include oxidative and nonoxidative coupling of substrates such as olefins, dienes, acetylenes, and aromatics; and various isomerization, disproportionation, hydrogenation, dehydrogenation, car bonylation and decarbonylation reactions, as well as reactions involving formation of bonds between carbon and halogen, nitrogen, sulfur, and silicon. The books by Peter M. Maitlis - The Organic Chemistry of Palladium, Volumes I, II, Academic Press, 1971 - serve to classify and identify the wide variety of reactions, and access to the vast literature is available through these volumes and more recent reviews, including those of J. Tsuji [Accounts Chem. Res. , 6, 8 (1973); Adv. in Organometal. , 17, 141 (1979)], R. F. Heck [Adv. in Catat. , 26, 323 (1977)], and ones by Henry [Accounts Chem. Res. , 6, 16 (1973); Adv. in Organometal. , 13, 363 (1975)]. F. R. Hartley's book - The Chemistry of Platinum and Palladium, App!. Sci. Pub!.

Palladium-catalyzed allylic C-H acetoxylation has been the subject of significant study in its 60-year history, however several limitations still exist. There are no methods for the allylic acetoxylation of terminal alkenes that exhibit high catalytic turnover. This is of considerable interest in order to establish large scale reactions. Reactions with a broad scope in substrate and coupling partner are also relatively sparse. In order for the field to continue to move forward, it is critical to understand the mechanistic systems so the insights can be applied to develop new methods that are broad in scope and robust in catalytic activity. This thesis will focus on mechanistic investigations to understand the mechanism of 4,5-diazafluoren-one (DAF)/Pd(OAc)[2]-catalyzed aerobic allylic C-H acetoxylation reactions, as well as develop methods that will expand the scope and increase the catalytic activity of allylic acetoxylation.Chapter 1 analyzes high turnover methods for Pd-catalyzed allylic acetoxylation with a focus on the factors that contribute to the success of existing catalytically robust methods, as well as the challenges with developing high turnover methods for terminal akenes and how recent advances with this substrate class may provide insights into unlocking reactivity. Chapter 2 presents the development of a method for Pd-catalyzed aerobic allylic acyloxylation with a low stoichiometry of carboxylic acid coupling partners. Chapter 3 provides an in-depth mechanistic investigation into 4,5-diazafluoren-9-one (DAF)/Pd(OAc)[2]-catalyzed aerobic allylic C-H acetoxylation by using operands spectroscopy to elucidate the two distinct rate regimes. Chapter 4 probes the role of benzoquinone additives in DAF/Pd(OAc)[2]-catalyzed aerobic allylic acetoxylation in the presence and absence of Co(salophen), a transition metal cocatalyst. Chapter 5 presents the development of a method for high turnover DAF/Pd(OAc)[2]-catalyzed allylic C-H acetoxylation of a terminal alkene as well as preliminary kinetics to probe the mechanism.

This book deals with the search for environmentally benign procedures for the oxidation of alcohols and gives an overview of their transition-metal-catalyzed aerobic oxidation.

Palladium catalyzed oxidative transformations that employ readily available molecular oxygen as the stoichiometric oxidant enable economic synthetic routes to complex organic targets. This thesis focuses on the development of aerobic oxidative transformations that generate carbon-nitrogen bonds. Chapters 2 and 3 describe research projects that have expanded the scope and mechanistic understanding of reactions that involve amidopalladation of alkenes (aza-Wacker reactions). Chapters 4, 5 and 6 describe research projects that have targeted the discovery of aryl C-H amination reactions. Palladium catalyzed aerobic C-H amination reactions have limited precedent. Several approaches to address this challenge were tested, and promising results are discussed.