No Catalyst Required: New Thermally-Promoted Transformations of Iminyl Radicals for the Synthesis of Complex Molecules

Brigham Young University, Provo UT

Investigators

Abstract

With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Steven L. Castle of Brigham Young University is developing new reaction methodology for synthesizing organic molecules. These reactions are triggered by thermal energy (i.e., microwave irradiation or conventional heating) and do not require the addition of external catalysts. The advantages of this approach when compared to other, more conventional strategies to similar entities include its simplicity, the lack of expensive or extravagant reagents or catalysts, the scope of the molecules that can be subjected to and generated from this chemistry, and the relatively short reaction times that are required for initiation and product formation. As a result, these new methods provide efficient synthetic routes to important classes of compounds, including some with potential as pharmaceuticals. In addition to developing the chemistry, Professor Castle and his students plan to advance STEM (science, technology, engineering and mathematics) education by creating lesson plans that will help high school chemistry teachers to incorporate organic chemistry into their courses. By exposing students to organic and medicinal chemistry far sooner than they normally would be, it is hoped that high school students will develop a deeper appreciation for chemistry and this has the potential to encourage them to consider pursuing STEM pathways in their education and professionally. The students that are directly participating in this project are receiving training in experimental techniques, troubleshooting chemical reactoins, communication, and critical thinking that will provide them with valuable tools to pursue careers in STEM fields. Under this award, Professor Steven Castle and his research group will generate iminyl radicals under thermal conditions by inducing the homolytic cleavage of relatively weak N-O bonds that are present in readily available O-aryl oxime ethers. This process affords high energy iminyl radicals that are capable of undergoing a variety of chemical transformations including intramolecular processes. These include cyclization reactions with pendant alkenes and hydrogen atom abstraction reactions with hydrogens that are a prescribed distance from the iminyl nitrogen atom. The radicals are also capable of being trapped intermolecularly to forge new C-C, C-N, C-O, C-S, or C-X (X = halogen) bonds. In addition to studying the fundamental generation and reactivity of iminyl radicals, the utility of this methodology is to be demonstrated through the planned convergent synthesis of fortuneicyclidin, with iminyl radical cyclization being the key step. This architecturally novel alkaloid natural product has yet to be synthesized in the laboratory and the proposed route has the potential to demonstrate real utility of the proposed iminyl radical-based tandem cyclization chemistry. 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.