Diazirines and Diaziridines as Nitrogen Transfer Reagents

With the support of the Chemical Synthesis Program in the Division of Chemistry, Justin Lopchuk of H. Lee Moffitt Cancer Cente in Tampa, Florida is studying the development of new methods and reagents to form carbon-nitrogen (C-N) bonds. This work is expected to have broad impact because nitrogen-containing compounds are valuable in pharmaceutical science, agricultural chemistry, chemical biology and in many materials/polymers. The methods being developed use a single reagent to create high value C–N bonds from a range of commercially available starting materials. Students doing this work will be trained in fundamental chemical principles, catalysis and the synthesis of complex organic molecular scaffolds of relevance to therapeutics. The broader impacts of the funded project include the creation of a diverse, nitrogen-rich compound screening library for chemical biology/biological discovery that will be made available to other researchers along with educational workshops and recurring virtual conferences. These latter efforts are being developed to provide opportunities for undergraduate and graduate students to network and to receive wider exposure for their research. This project is expected to expand the scope of amination reagents and contribute to both the late-stage amination of complex scaffolds and to developing a more diverse set of N-containing architectures, including N–containing heterocycles. More specifically, the Lopchuk group is focused on the use of diazirines and diaziridines (three-membered rings with two nitrogens and one carbon) as novel amination reagents. In this approach diazirines will be used in reactions with structurally diverse starting materials to form diaziridine intermediates that are subsequently converted into amines (including 15N stable labeled amines), hydrazines, and nitrogen-containing heterocycles such as pyrazoles, indazoles, and pyrroles. The use of diazirines and diaziridines avoids many of the drawbacks that have been seen with other electrophilic and radical amination reagents including their instability, their lack of functional group tolerance, and/or the harsh conditions needed for processing them downstream of C–N bond formation. 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.