RUI: Nitrogen as an Enabling Linchpin for Complexity-Building Based on (5 + 2) Cycloadditions

Board Of Trustees Of Illinois State University, Normal IL

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Andrew Mitchell of Illinois State University and Professor Dean Tantillo of UC-Davis are developing new chemical reactions that have connections to biology, medicine, physics, materials, environmental sustainability, and other areas. Professor Mitchell and his undergraduate students study important reactions called cycloadditions in the laboratory and Professor Tantillo and his students use high-powered computer technology to aid in understanding the inner workings of each molecule involved. In addition, they collaborate with Professor Corey Stephenson and his students at University of Michigan who study reactions that are promoted by visible light, which is an important and sustainable alternative to environmentally detrimental chemicals. These reactions enable the selective transformation of two dimensional flat molecules into three-dimensional building blocks, which resemble a number of biologically active compounds and medicines. Although new reaction discoveries are fascinating, the Mitchell and Tantillo groups are equally passionate about training next generation scientists, many of whom are from underrepresented groups, to ask important questions within an organic chemistry CORE (Collaboration, Outreach, Research, Education) curriculum. Collaboration invites students to work with other established scientists and scientists in training. Deep understanding of these reactions is obtained by creativity, teamwork, communication, and characterization of new compounds, skills that are often caught more than taught. For example, students learn to think on their feet and engage in nuanced scientific discussions during lab work and group meetings. Outreach provides opportunities for local high school students to hear stories about historical and current science. Research in the undergraduate environment opens the door for greater sophistication through mentorship, critical reasoning, and exposure to state-of-the-art instrumentation at Illinois State and beyond. Oxidopyrylium-based [5+2] cycloadditions are exceptionally useful reactions that result in the construction of important heterocyclic small molecules. The Mitchell group has demonstrated that this reaction can lead to previously undiscovered scaffolds but that the reaction suffers from regioselectivity issues. To overcome this problem, they have chosen to employ nitrogen as a traceless tether as a means of controlling the reaction’s regioselectivity. Synthetic and mechanistic studies in collaboration with the Tantillo and Stephenson labs will expand these experiments, establish the use of traceless tethers as a means of controlling the reaction, and explore the photochemical activation of the reactions to discover new pathways. 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.