Reaching New Horizons in Iminyl Radical Chemistry via Microwave Irradiation

Brigham Young University, Provo UT

Investigators

Abstract

With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Steven L. Castle of Brigham Young University. Professor Castle is developing new methods for synthesizing organic molecules that are facilitated by microwave energy rather than by catalysts or reagents that are often toxic, hazardous, or expensive. In comparison to traditional organic synthesis techniques, these methods are providing safer, more sustainable, and more efficient routes to compounds that have potential application as pharmaceuticals. A key innovation is the use of microwaves to trigger cascade processes that convert simple precursors into complex and useful compounds by enabling a sequence of chemical transformations to occur in a controlled fashion. Professor Castle and his students are impacting STEM education by creating lesson plans that will assist high school chemistry teachers with incorporating organic chemistry into their courses. These plans are designed to inspire high school students to pursue STEM careers by exposing them to the exciting world of organic chemistry and teaching them about the positive impact that chemistry has on human health and quality of life. Professor Castle and his co-workers employ O-aryl oxime ethers as precursors of iminyl radicals. Upon irradiation with microwaves, these species undergo direct homolysis of the O-N bond. The resulting iminyl radicals are then transformed by either cyclization or hydrogen atom abstraction (i.e., C-H activation). In both cases, a radical intermediate is formed and subsequently trapped by a reagent that forges a new C-C, C-N, C-O, C-S, or C-X bond. By generating iminyl radicals under nonreducing conditions in the absence of metal catalysts or redox cycles, these reactions permit a wide range of functionalized radical traps to be used. Additionally, the cyclizations are stereoselective and can be incorporated into cascade processes. The utility of these microwave-based methods is being demonstrated through the efficient construction of a member of the securinega family of alkaloids. The student participants in this project are receiving training in experimental techniques, troubleshooting, communication, and critical thinking that will enable them to pursue careers in chemistry or other STEM fields. 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.