RUI: Exploration of [5+2] Cycloadditions toward Novel Heterocyclic Scaffolds

Board Of Trustees Of Illinois State University, Normal IL

Investigators

Abstract

The Chemical Synthesis Program of the NSF Chemistry Division supports the project by Professor Andy Mitchell in the Department of Chemistry at Illinois State University. Professor Mitchell and his students are developing new chemical reactions that form molecules comprised of rings of atoms. These new reactions are important in organic chemistry because they enable efficient and selective transformation of simple molecules to three-dimensional molecules of greater complexity. Many biologically active molecules and pharmaceuticals have three-dimensional structures similar to those constructed by these reactions. More generally, developments in organic chemistry advance the fields of biology, medicine, and materials, as well as promoting economic development and environmental sustainability. Undergraduate student research training performs an indispensable role in the growth of students into scientists. Through hands-on mentorship and exposure to state-of-the-art instrumentation, Professor Mitchell prepares undergraduates to continue their training at excellent graduate school programs or to enter the workforce as productive chemists. The Mitchell group pursues synthetic challenges with potential for enduring and broad impact, yet with manageable goals suitable for novice researchers. In addition, Professor Mitchell partners with the Illinois Summer Research Academy to mentor high school students, often from underrepresented groups. This intensive one-week research experience can provide the spark necessary to excite these young students with the wonders of organic synthesis. The main objective of the proposed research is to expand the chemical space that is accessible by cycloaddition reactions in order to construct novel and otherwise inaccessible heterocyclic scaffolds. Specifically, the Mitchell group is investigating the scope and reaction pathway of various oxidopyrylium-based [5+2] processes. Utilizing the Feist-Bénary furan synthesis, they are working toward the synthesis of toxicodenane A and developing a diastereoselective [5+2] three-carbon component. In a new direction, they are establishing activation parameters toward oxidopyrylium intermediates. They use this information to develop reactions that address current selectivity limitations. As part of broader impacts, next generation scientists are trained to ask important questions in the context of biologically relevant molecules. The educational plan includes outreach to local high schools to introduce students to the historical and current significance of organic synthesis. High school students are mentored in a research lab through the Illinois Summer Research Academy. These outreach activities are well integrated with the research program.