Anionic and Pericyclic Reaction Cascades for Organic Synthesis

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With the support of the Chemical Synthesis Program in the Division of Chemistry, Professor Njardarson of The University of Arizona is studying new classes of chemical reactions that will lead to more efficient methods for the manufacture of compounds of importance to society, such as pharmaceutical agents, agrochemicals, and advanced materials. The insights gained from the studies, which will encompass powerful multiple bond-forming 'cascade' reactions capable of rapidly generating all manner of molecules of interest, are anticipated to inform on the future practice of synthetic design. The broader impacts of the funded project also include the education and training of the student coworkers taking part in the research and extend to enabling Prof. Njardarson's continued development of innovative and freely accessible educational content for the general public. In this regard, the award will support an expansion to the content available on the PI's popular app and website 'Chemistry By Design (CByD)', with concurrent transformation of current and future content to a machine-readable format that should be compatible with emerging artificial intelligence/informatics technologies in the chemical synthesis field. The well-established "Top 200" family of posters form the Njardarson group on the structures and properties of pharmaceutical drugs will continue to be produced and made available annually in traditional and new custom content formats.This project will involve continued and significantly expanded investigations of the new class of counterion-dependent anionic asymmetric amino-Cope rearrangements recently introduced by the Njardarson group. This versatile reaction platform affords access to a range of complex enantioenriched chiral products (both cyclic and acyclic molecules) from readily available starting materials; however, much remains to be learned about its scope before the power of the approach can be fully realized. New work will include establishing methods for the selective trapping and exploitation of chiral enamide intermediates and studying the many possible in situ cyclization scenarios. These efforts will also include novel ways to streamline synthesis of the requisite amino-Cope precursors (conjugated chiral imines) while also exploiting the discovery of new useful cascades that may outcompete the amino-Cope reaction. The second part of the funded project is focused on the development of new transformations for the assembly of high value densely substituted aromatic structures such as pyridines, isoquinolines, and other arenes, from simple acyclic building blocks via pericyclic-centered reaction cascades. It is anticipated that a number of significant new and useful methods for the elaboration of sought after acyclic and cyclic products from simple starting materials, will emerge from the research program.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.