Transition Metal-Catalyzed Functionalization of Diazirines

In this project, Professor Ross A. Widenhoefer in the Department of Chemistry at Duke University will develop transition metal-catalyzed bond forming processes between carbon and other elements using diazirine reagents. Diazirines are reactive three-membered rings containing one carbon and two nitrogen atoms. The project will develop new catalysts, elucidate the key catalyst attributes that enable diazirine activation and subsequent functionalization, and expand the scope of these reactions. These catalytic processes will convert readily available chemical feedstocks into value-added products with potential applications to pharmaceutical development, agrochemistry, synthesis, and chemical biology. These research activities will be fully integrated into the scientific education and training of the graduate and undergraduate student researchers. Graduate and undergraduate students participating in the proposed activities, particularly those interested in academic careers, are encouraged to augment their training through participation in educational activities offered through the Duke Chemistry Department and Duke University Graduate School. Graduate students and undergraduate students will participate in community outreach activities through the Duke Chemistry Outreach program. Building on preliminary results that established weakly ligated Pt(II) complexes as efficient catalysts for diazirine to alkene carbene transfer (cyclopropanation), Prof. Widenhoefer and his team will identify new catalysts for diazirine to alkene carbene transfer with a focus on ligand-controlled selectivity and, in doing so, will elucidate the electronic and structural features that facilitate diazirine activation and subsequent carbene transfer. The team will likewise investigate the mechanisms of catalytic diazirine to alkene carbene transfer, with a focus on the intimate mechanisms and microscopic steps involved in diazirine activation. The project also seeks to expand the scope of catalytic diazirine to alkene carbene transfer to include a more diverse range of diazirines and alkenes and to extend catalytic diazirine functionalization to include carbon-hydrogen and element-hydrogen carbene insertion processes. Owing to the enhanced stability and greater diversity of substitution of diazirines relative to the widely employed diazo compounds, development of transition metal-catalyzed carbene transfer processes employing substituted diazirines will (1) mitigate many of the safety concerns associated with the use of diazo compounds, (2) significantly expand the scope of these methods with respect to carbene substitution, and (3) facilitate application of catalytic carbene transfer to large-scale synthesis and increased utilization in industrial settings. 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.