Heterogeneous Directed Hydrogenation of Arenes and Olefins with Chemo- and Stereoselectivity

Project Summary/Abstract Heterogeneous noble metal catalysts are commonly used in organic synthesis for the hydrogenation of unsaturated organic functionality because of their fast reactivity and ease of purification. However, heterogeneous catalysts tend to be poorly selective in the presence of other reducible functionality and incapable of achieving stereoinduction due to the two-dimensional nature of the catalyst surface. Taking inspiration from the homogeneous literature on substrate- directed reactivity, the Li group recently demonstrated the first example of a heterogeneous hydroxyl-directed hydrogenation. Using a bimetallic alloy catalyst containing a noble metal and a base metal, we were able to catalyze highly diastereoselective hydrogenations of cyclic olefins by simultaneously adsorbing the hydroxyl directing group onto the base metal atom and the olefin onto the noble metal site. The overarching goal of this proposed research is to demonstrate that directed reactivity using bimetallic alloys is a general strategy to achieve chemo- and stereoselective hydrogenation of drug-like compounds. These selective hydrogenation reactions will be utilized to increase the sp3 content, three-dimensionality, and structural diversity of pharmaceutical candidates. We will develop new bimetallic nanoparticle compositions in order to extend the directed hydrogenation concept to systems that are not accessible using molecular catalysts, including arenes and heteroarenes, amine-directed reactions, and substrates where the directing group and reactive moiety are located remote from one another. We will also explore directing effects in dictating chemo- and regioselectivity in substrates where multiple reducible functional groups are simultaneously present. In parallel with the development of synthetic methods, we will conduct detailed nanomaterials characterization, in-situ surface spectroscopy, and kinetic studies in order to elucidate the surface ensemble required for high directivity. Together, this research program will provide new heterogeneous catalysts and methods for selective, late-stage transformations in biologically-active compounds.