. Oxidation reactions are essential for both functional group manipulation and heteroatom introduction in the synthesis of biologically relevant compounds. Additionally, newly discovered and significantly improved oxidative processes can have a direct effect on the efficiency of, and approaches to the execution of targeted syntheses. Therefore, the development of selective, practical oxidation reactions is a continuing challenge facing chemists in both academia and industry. A key consideration in developing oxidation reactions is selection of the stoichiometric oxidant where versatility, expense, and environmental impact need to be addressed. An attractive approach is the use of metal-catalyzed oxidations coupled to a practical terminal oxidant such as molecular oxygen or hydrogen peroxide. Therefore, a central goal of oxidation catalysis and this program is the discovery of highly active, robust catalysts capable of using practical oxidants. Based on this goal, palladium catalysts have been selected due to their ability to effectively use molecular oxygen as a terminal oxidant in oxidation catalysis and promote cross-coupling reactions forming a vast array of C-C, C-N, C-S, and C-O bonds. A fundamental goal of the proposed research is to integrate Pd-catalyzed oxidation reactions with cross-coupling processes and ultimately generate mature synthetic methods applicable in both industry and academia for the synthesis of biologically relevant compounds. The current proposal is directed toward the development of new Pd-catalyzed olefin functionalization reactions. Specifically, we will (1) study and develop our recently discovered Pd-catalyzed aerobic hydroalkoxylation reactions of styrenes containing a phenol, (2) develop and investigate Pd-catalyzed hydroalkoxylation reactions of styrene derivatives, (3) explore Pd-catalyzed cross-coupling reactions utilizing organometallic reagents paired with an aerobic alcohol oxidation to functionalize olefins, (4) develop and expand a Pd-catalyzed aerobic dialkoxylation of styrenes containing a phenol, (5) investigate the scope and mechanism of a recently discovered ligand-modulated direct dioxygen-coupled Wacker oxidation. The proposed research described herein will be approached using method discovery and development facilitated by elucidation of mechanistic details using physical organic chemistry techniques.
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