Modular chemocatalysts for tunable and predictable C-H functionalization

University Of Wisconsin-Madison, Madison WI

Investigators

Abstract

With the support of the Chemical Catalysis and the Chemical Synthesis Programs in the Division of Chemistry, Professor Jennifer M. Schomaker of the University of Wisconsin is studying the development of new earth abundant and inexpensive catalysts to transform feedstock chemicals from petroleum and biorenewable sources into valuable building blocks for pharmaceuticals, agrochemicals, polymers, and fuels. The carbon-hydrogen (C–H) bond is the most common type of chemical bond in organic compounds and it can be transformed into more valuable bonds, including carbon-nitrogen (C–N) bonds. However, it is challenging to achieve selectivity for a desired reaction at only one specific C–H bond when there are multiple different C–H bonds in a molecule. In this project, Professor Schomaker’s group is expanding the design of low-cost silver catalysts to transform C–H bonds into C–N bonds in high yields and using this knowledge to develop even less expensive catalysts based on the earth abundant metals iron and copper. These catalysts generate less waste, deliver several useful products from a single starting material, and streamline the preparation of selected commercial drugs that contain at least one C–N bond. In terms of broader impacts, Professor Schomaker participates in outreach programs to educate and engage the general public, especially young women, in science. Her studies are aimed at making her laboratory’s research and new catalysts appealing to industry by showing how water can be used as an environmentally sustainable solvent, exploring efficient electrochemical methods to reduce waste streams, and collaborating with industry partners. Graduate and undergraduate students benefit from these broader impacts through exposure to real world applications of their chemistry and by receiving co-mentoring from industrial colleagues. The work being carried out in this project is expected to lead to the development of low-cost, modular catalysts based on silver, iron and copper for the tunable functionalization of C–H bonds to upgraded C–N bonds. To address this issue, Professor Schomaker is pursuing both the fundamental understanding and the practical applications of new catalytic systems able to achieve predictable catalyst control of the chemo-, site-, and stereoselective transformations of C–H bonds to C–N bonds through metal-catalyzed nitrene transfer processes. She also plans to extend the utility of these catalysts to selectively transform C–H bonds into more valuable C–C and C–O bonds. These investigations will combine mechanistic, spectroscopic, and computational studies (density functional theory and higher-level ab initio methods such as CASSCF) to understand how the features of diverse and easily prepared N- and P-donor ligands influence: 1) the electronic structures of the resulting metal nitrenes and carbenes, 2) the dynamic behavior of reactive intermediates, 3) non-covalent interactions between the substrate and catalyst to control site-selectivity of the C–H functionalization, and finally, 4) the ability to develop general, modular, and readily accessible catalysts for enantioselective nitrene transfers. Ultimately, this work aims to establish universal design principles to sustainably facilitate non-directed C–H functionalization that overrides innate reactivity preferences. The scientific broader impacts of this work will be expanded by applying these principles to a diverse range of transition metal-catalyzed C–H bond oxidations. Additional broader impacts include the ability to use non-chlorinated solvents for these transformations, the employment of electrochemical methods to replace stoichiometric oxidants, and the collaboration with industrial partners in targeting late-stage modifications of drug scaffolds. 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.