CAS: Copper Catalyzed sp3 C-H Functionalization

With the support of the Chemical Catalysis Program of the Division of Chemistry, Professor Timothy H. Warren of the Department of Chemistry at Michigan State University is studying how to add function to molecules through normally unreactive carbon-hydrogen (C–H) bonds using copper-based catalysts. This research aims to create more efficient, environmentally friendly, and cost-effective ways to build important chemical structures, such as those found in medicines and materials. By developing new methods to modify the most abundant types of carbon-hydrogen bonds in organic molecules, this project will help scientists streamline the synthesis of complex molecules and explore new chemical space. The broader impacts of the work include hands-on training for high school students, undergraduates, and graduate students enhanced through collaborations with industrial and academic partners. Outreach activities that include science festivals and mentorship programs will help inspire the next generation of scientists. This project will establish new catalytic protocols to transform strong, unreactive sp3 carbon-hydrogen bonds in molecules and materials to carbon-nitrogen, carbon-oxygen, carbon-sulfur, and carbon-carbon bonds. These C–H functionalization methods provide access to areas of chemical space that are difficult to reach using traditional synthetic approaches. Copper catalyzed radical relay approaches will enable new synthetic methods for C-H arylation, alkylation, and vinylation reactions with broad applicability. Copper nitrene-based methods will allow metal-centered control over site selectivity in C-H amination, allowing functionalization of stronger, more accessible primary C–H bonds even in the presence of weaker secondary and tertiary ones. Mechanistic studies of reactive copper intermediates – including underexplored copper(II) alkyl species - serve as a unifying foundation, informing the development of more efficient and selective catalytic systems. This project expands the synthetic toolbox for late-stage molecule diversification and polymer functionalization and informs broader catalytic strategies in organic chemistry. 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.