| Today, natural products remain the most abundant source of lead compounds for new drug discovery, and as such, natural product total synthesis remains a venerable goal. In Chapter I of this work it was our endeavor to develop a unified approach to optically active, functionalized heterocycles of differing ring sizes. Because optically active heterocycles are the core of the vast majority of natural products, such a methodology could be a foundation supporting synthetic approaches to multiple classes of naturally occurring compounds. Towards that goal, we have shown that asymmetric intramolecular Heck cyclization of endocyclic enamides (i) occurs at room temperature to give functionalized indolizidinone (ii) and azaazulone (iii ) in up to 86% enantiomeric excess. To demonstrate the utility of this methodology a total synthesis of (+)-5-epiindolizidine (iv) and indolizidine 223AB (v) is described. Chapter II describes our efforts directed toward the total synthesis of the marine derived macrocyclic natural product upenamide (vi). The synthesis will utilize an enamide-based approach to assemble the upper bicyclic aminal moiety and an enantioselective Diels-Alder cycloaddition to assemble the lower spirooxaquinolizidinone ring system.*; In modern organic synthesis, organometallic catalysis plays an ever increasing role in carbon-carbon bond construction. Palladium coupling reactions are ubiquitous in current literature and the desire for efficient palladium catalysts is strong. Chapter III explores the synthesis and study of new PCP-type palladium catalysts vii–ix. The overarching goal of this work was to utilize the known stability of PCP-type catalysts in order to develop a chiral, reusable, polymer bound PCP catalyst for palladium mediated coupling reactions.; *Please refer to dissertation for diagrams. |
