Development of Immobilized Chiral Bronsted Acids and Their Exploration in Asymmetric Catalysis

About This Grant

With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Pavel Nagorny of the University of Michigan is developing new recyclable catalysts that promote chemical reactions resulting in enantiomerically enriched (chiral) products. Access to molecules in their enantioenriched form is critically important for drug discovery, as it affects key molecular characteristics such as therapeutic potency, thereby underscoring the need for catalysts that can selectively form these molecules. The Nagorny research group has expertise in designing and using polymers that embed chiral acid catalysts. Professor Nagorny and his students will investigate how these catalysts work and will optimize them for the synthesis of molecular fragments commonly found in pharmaceuticals. It will generate new knowledge about organic molecule reactivity that advances the fields of catalysis, polymer chemistry, and asymmetric synthesis. The resulting techniques and catalysts will enable chemists to shorten synthetic sequences and develop chemical processes that are safer and more sustainable, thereby saving time, money, and natural resources. These studies will also be used to train graduate and undergraduate students who plan to pursue careers in the chemical and pharmaceutical industries, biomolecular science, and medicine. Professor Nagorny and his students will also participate in various training and outreach efforts focused on attracting K–12 students to STEM fields. With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Pavel Nagorny of the University of Michigan is developing new polystyrene-based chiral Brønsted acids and using them as recyclable catalysts for asymmetric organocatalysis in both batch and continuous flow setups. These catalysts will be synthesized using approaches designed to enable late-stage modifications of advanced intermediates, allowing the generation of multiple catalysts in a minimal number of steps, thereby simplifying the process of catalyst tuning. The project will target the immobilization of the best-performing classes of Brønsted acid catalysts, such as monomeric BINOL-based chiral phosphoric acids (CPAs) and dimeric, spatially confined imidodiphosphates (IDPs). The resulting polymeric catalysts are designed to be easily recovered and recycled, and will be employed in both new and established asymmetric transformations, such as transfer hydrogenation, allylation, acetal formation, and cycloaddition reactions. In addition, new strategies aimed at streamlining asymmetric reaction optimization with immobilized catalysts in continuous flow will be pursued to accelerate the discovery of optimal reaction conditions and reagents. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.