SusChEM: The Versatility of Electrophilic Metal N-Aryl Catalytic Intermediates for Carbon-Nitrogen Bond Formation

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The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Tom G. Driver. Professor Driver is a faculty member in the Department of Chemistry at the University of Illinois at Chicago. He is exploring the reactivity of metal-nitrogen catalytic intermediates for the formation of carbon-nitrogen bonds. The goal of this project is to develop new metal-catalyzed processes to form challenging nitrogen-containing heterocycles in molecules that exhibit important biological and electronic properties. Nitrogen heterocycles are pervasive in pharmaceutical agents that have been shown to improve the quality of life and health of humans. The hypothesis-driven nature of the project is well suited for the education of scientists at all levels. Professor Driver's research team includes undergraduate and graduate students, including women and underrepresented minorities. He has established an environment for students to advance in their professional development. The project includes research experiences for high school students to inspire their pursuit of careers in science, technology, engineering and mathematics fields.Nitrogen heterocycles are pervasive in pharmaceuticals and natural products that may improve the quality of life and health of humans. Simplifying access to functionalized nitrogen (N)-heterocycles is useful for the advancement of biological and medicinal studies. The experiments being conducted use the novel reactivity of electrophilic metal N-aryl catalytic intermediates in the development of new carbon-nitrogen bond-forming reactions of aryl azides and nitroarenes. The projects address gaps in state-of-the-art methods to access complex, functionalized N-heterocyclic compounds through construction of carbon-nitrogen and carbon-carbon bonds by developing synthetic methods that are mechanistically distinct from existing protocols. Towards that end, the principle investigator's goals are to: (1) develop new metal-catalyzed domino carbon-hydrogen amination reactions to efficiently access N-heterocycles from aryl azides; (2) synthesize N-heterocycles from nitroarenes through a metal-catalyzed cyclization-migration sequence or carbon-hydrogen amination; (3) achieve intermolecular sp2 and sp3 carbon-hydrogen amination reactions using nitroarenes; (4) determine if the reactivity patterns observed for electrophilic metal N-aryl nitrenes are a general phenomenon of divalent catalytic intermediates by studying metal-carbenes formed from N-tosylhydrazones. The compounds resulting from these studies are added to the University of Illinois at Chicago Center (UICentre) for Drug Discovery's novel small molecule library and submitted to Professor Driver's High-Throughput Screening (HTS) facility in order to initiate new collaborations. This project serves as means for the training of students to advance in their scientific careers. By emphasizing the participation of female and underrepresented minority students, this program helps meet the goals outlined by PCAST (President's Council of Advisors on Science and Technology) to transform and improve the science, technology, engineering and mathematics (STEM) student pipeline.