Synthetic Methods to Generate Encarbamates and Nitrogen Containing Compounds

With the support of the Chemical Synthesis Program in the Division of Chemistry, Dr. Brewer of the University of Vermont is studying new reactions to prepare organic structures. These fundamental studies are important because discovering new ways to prepare organic molecules enables advances in many related fields of research including drug discovery and materials science. A key focus of this work is developing a new ring opening reaction that will produce a synthetically useful class of compounds, called encarbamates, that have received minimal attention from chemists and the studies being conducted under this award will enable their use in a variety of syntheses. This research will provide new routes to molecular scaffolds that contain nitrogen atoms, which take advantage of a more stable and easier to isolate intermediate than other systems. This is important because nitrogen containing compounds are ubiquitous in chemistry and common in medicines and this research has the potential to impact the field of medicinal chemistry. This funding will also impact STEM workforce development as the students who work on this project will receive training in synthetic organic chemistry and will learn to conduct mechanistic studies, reaction optimization and development studies, and will become adept at compound characterization and structure elucidation. Professor Brewer will also be engaged in student training and outreach programs. This research is a fundamental investigation into the reactivity of oxazolidinones in the presences of an activating agent and base to prepare N-vinyl carbamates through a putative azomethine ylide intermediate. Importantly, the ring opening of oxazolidinones provides a method to form 2-(N-acyl)amino-1,3-dienes, which have not received thorough study from the synthetic community because there are few convenient and reliable ways to prepare them. This research addresses that gap by providing the synthetic community with a new way to access these intermediates. These diene products will be studied as reaction partners in Diels-Alder cycloaddition reactions to give cyclic N-vinyl carbamates. These studies will benchmark the reactivity of these dienes in cycloaddition reactions and provide insight into the scope of these reactions. These fundamental studies will make 2-(N-acyl)amino-1,3-dienes more useful to the synthetic community and ultimately this research will provide novel and efficient ways to prepare structurally-complex biomedically-relevant compounds, or basic but important molecular scaffolds that contain amines. 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.