Enantioselective, Metal-Catalyzed Alkynylations of Oxocarbenium & Iminium Ions

With the support of the Chemical Synthesis Program in the Division of Chemistry and the Office of Strategic Initiatives, Professor Mary Watson of the University of Delaware is studying the development of new methods for the synthesis of cyclic molecules containing oxygen and nitrogen atoms. The products of these methods are of societal importance in pharmaceutical, natural product, polymer, and other material applications. Preparing these molecules as single three-dimensional geometrical isomers, or “enantiomers,” is particularly significant in biomedical applications because opposite enantiomers often elicit different bioactivity. In this project, Dr. Watson and her research group are developing a catalytic strategy for the synthesis of oxygen and nitrogen heterocycles that will allow efficient access to molecules that are currently difficult to prepare as single enantiomers. Dr. Watson is also actively engaged in outreach activities to provide opportunities for students of all levels to engage in science. Her research program provides excellent training for undergraduate students through guided research opportunities. In addition, through outreach at the University-associated daycare, Dr. Watson is exciting young children (pre-school through third grade) about science and scientific careers. This project focuses on developing enantioselective copper-catalyzed additions of alkynes to cyclic oxocarbenium and iminium ion intermediates to deliver oxygen and nitrogen heterocycles with both tri- and tetrasubstituted stereocenters adjacent to the heteroatom. Due to the prevalence of disubstituted heterocycles in bioactive molecules, enantioselective difunctionalization approaches are being established to efficiently increase the complexity and value of simple achiral starting materials. In addition, enantioselective alkynylation of a variety of cationic intermediates are being investigated to provide efficient access to a wide range of heterocyclic products, which may be derivatized into valuable acyclic amines with tetrasubstituted stereocenters or elaborated into natural products and natural product analogues. Students involved in this project are receiving training in chemical synthesis and enantioselective catalysis. 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.