CAREER: SusChEM: New organocatalytic approaches to the stereo- and regioselective construction of acetals

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With this award, the Chemical Catalysis Program of the Division of Chemistry supports the research of Professor Pavel Nagorny of the Department of Chemistry at the University of Michigan. This research project develops new chiral catalyst-controlled stereoselective transformations that proceed through highly reactive oxocarbenium ion intermediates. The chemistry of oxocarbenium ions is central to the synthesis of acetal-containing compounds such as carbohydrates and spiroketals, as well as heterocyclic compounds containing tetrahydrofuran and tetrahydropyran moieties. These functionalities are also present in numerous bioactive natural products as well as drugs and are often vital to the biological properties of these compounds. Harnessing the reactivity of oxocarbenium ions is a long-standing challenge, which is addressed utilizing chiral phosphoric acid-based catalysts to control the course of important transformations proceeding through the intermediacy of oxocarbenium ions. This project is focused on investigating catalyst-controlled stereo- and regioselective acetalization reactions. New chiral catalysts are synthesized and examined for the stereoselective/regioselective formation of spiroketals, acetals and glycosides. Structural and computational studies are performed to elucidate the mechanism of activation and the origins of selectivity. Mechanistic studies contribute to fundamental insights into catalyst structure and function, and provide opportunities for hypothesis-driven catalyst design. Professor Nagorny's research efforts revolve around the development of new chiral phosphoric acid-based transformations involving oxocarbenium ions and application of these transformations to the synthesis of bioactive compounds and natural products. These studies will produce new techniques that will enable the discovery of new small-molecule-based therapeutic agents and improve the understanding of fundamentally important chemical and biochemical processes. In addition, these efforts will advance the field of chemical synthesis and produce new catalysts that will allow chemists to shorten synthetic sequences, saving time, money and natural resources. This research is considered sustainable as it uses phosphorus-based catalysts (organocatalysts) rather than expensive, costly and sometimes toxic transition metal-based catalysts. In addition to the technical applications of the research, this project encourages sophomore undergraduate students to consider the historical, economic, social, psychosocial, societal and legal issues associated with pharmaceuticals design and production. Students will also be carefully trained to edit Wikipedia entries in order to learn how to explain their science to a broad and diverse audience.