Enantioselective, Metal-Catalyzed Alkynylations of Oxocarbenium and Iminium Ions

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Organic molecules containing oxygen and nitrogen atoms are prevalent in pharmaceuticals, natural products, polymers, and other materials. Many of these molecules are chiral, which means that they exist as non-superimposable mirror images. These mirror image structures often behave differently in biological systems. For example, chiral pharmaceuticals typically show different efficacy depending on which mirror-image structure is administered. Given their importance in biological and biomedical applications, it is therefore crucial to prepare these molecules as a single chiral structure, also known as an enantiomer. However, methods to prepare the desired enantiomer of many molecules are limited, and this curbs the discovery of potential medicines and biological probes. In this project, Dr. Mary Watson is developing a strategy using catalysts for the synthesis of oxygen- and nitrogen-containing cyclic compounds that will allow the efficient synthesis of molecules that are currently difficult to prepare as single enantiomers. The catalysts are themselves single enantiomers, and she is also studying the fundamental interactions between the catalyst and the organic substrates to enable broad understanding of the mechanism of these reactions, and especially how the chirality of the catalyst is ultimately conveyed to that of the chiral product. Dr. Watson is actively engaged in outreach activities that build upon her research to provide opportunities for students of all levels to engage in science. Her research program provides excellent training for undergraduate students through significant research opportunities. In addition, through outreach at the University-associated daycare, Dr. Watson is inspiring a diverse group of young children (pre-school through third grade) with excitement about science. With funding from the Chemical Synthesis Program of the Chemistry Division, Dr. Mary Watson of the University of Delaware is developing enantioselective catalytic methods for the synthesis of oxygen and nitrogen heterocycles with tri- and tetrasubstituted alpha-stereocenters. She is investigating the use of chiral copper catalysts to deliver terminal alkynes to cyclic oxocarbenium and iminium ion intermediates. Her focus is to enable efficient synthesis of highly enantioenriched oxygen and nitrogen heterocycle scaffolds that are difficult to prepare via conventional methods. She will also undertake rigorous mechanistic experiments to understand the structure of the active catalyst and determine a rationale for the high enantioselectivity observed in these reactions. Dr. Watson is actively engaged in science, technology, engineering, and mathematics (STEM) outreach programs focused on increasing diversity through student research experiences and demonstration programs at the University-associated daycare, in support of the broader impacts of this project.