Development of Strategies for the Synthesis of Heterocycles

Project Summary/Abstract Heterocycles are ubiquitous components of pharmaceutical drugs essential for human health. A particularly attractive approach to nitrogen containing heterocycles is the modification of cheap and readily available amines via C–H bond functionalization. However, methods that efficiently accomplish this task typically require the use of expensive transition metal catalysts and/or oxidants. This proposal is focused on the design and development of efficient and practical methods for amine functionalization, including the development of asymmetric variants. The main goal is the alpha- functionalization of amines through conceptually new and underdeveloped methods of substrate activation. Unique methods for the synthesis of heterocycles will also be explored in the context of asymmetric Lewis and BrØnsted acid catalysis. In addition to targeting the rapid preparation of compounds related to structures with known biological activities, efforts will center on the development of particularly powerful reactions that rapidly produce new polycyclic heterocycles. A priority is the generation of new structural frameworks that are absent from current drug discovery screening libraries.