Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products

With the support of the Chemical Synthesis program in the Division of Chemistry, Andrew G. Roberts of the University of Utah will develop new synthetic methodology for the generation of complex polyaromatic compounds and biologically important natural products. The new methodology involves iterative carbon-nitrogen bond formation and cleavage en route to the construction of new carbon-carbon bonds to generate the desired products. The planned research is grounded in fundamental organic chemistry principles. Dr. Roberts and his research team will establish the use of nitrogen-containing molecules (tertiary amines) as templates for the assembly of carbon–carbon bond-containing compounds that are difficult to obtain by other synthetic routes. These research efforts will serve to train multiple students at the graduate and postdoctoral levels in the practice of modern organic synthesis. The planned Broader Impacts activities will align the chemistry research with productive outreach programs that include chemistry visualization workshops and science, technology, engineering, and mathematics (STEM) promotion efforts through the integration of organic chemistry-based scientist spotlight assignments in a sophomore-level organic chemistry course. The scientific goal of this research is to understand the fundamental reactivity of tertiary amines and amine-derived intermediates in transformations that involve carbon–nitrogen bond cleavages. Efforts toward this broader goal will establish amine rearrangement and deaminative methods for complex molecule synthesis. Preliminary research shows that tertiary amines can undergo iterative methylation; rearrangement reactions to enable the formation of difficult carbon–carbon bonds. The proposed research will involve the design and application of synthesis logic to prepare simple tertiary amine substrates, the use the tertiary amine to template carbon–carbon bond forming cyclization reactions, and rearrangement or deamination of the template with the formation of difficult-to-access carbon–carbon bonds of the target products. The planned experiments will optimize reactivity for amine methylation and ammonium-based group transfer chemistry, establish mechanistic understandings for amine rearrangement and deaminative reactions, and incorporate developed methods to complete concise syntheses of important polycyclic molecules and bioactive natural products. 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.