Nickel Catalyzed Electrochemical C-C Cross-Coupling Reactions - Project Summary. This proposal describes the collaborative research activities by Liu (PI) and Ess (co-PI) towards developing highly effective, sustainable, green Nickel (Ni) catalyzed electrochemical cross-coupling reactions for synthetic applications in making pharmaceuticals and bioactive molecules, and integrated education activities aimed at promoting research experiences of undergraduate, and graduate students. Special emphases will be placed on attracting and training underrepresented Native American students. The new knowledge obtained from this proposed research will provide guidance in developing competent and atomically economic electrosynthesis approaches for their utilization in developing pharmaceuticals and bioactive molecules, thereby enhancing human health and enabling the sustainable development of our society. Herein, we propose that redox neutral electrochemical C?C cross-coupling reactions can be accomplished in an undivided cell configuration using bench-stable electrophiles (aryl halide, alkenyl halides, and alkynyl halides) and nucleophiles (organic trifluoroborate, carboxylates, and amines), non-precious, bench-stable catalysts consisting of a NiII pre-catalyst and polypyridine ligands under ambient conditions. Preliminary studies have confirmed the broad reaction scope and good yields of the Ni-catalyzed electrochemical coupling reactions by 50 examples of aryl/β-styrenyl chloride/bromide and benzyl trifluoroborates. Their potential applications were demonstrated by electrosynthesis and late-stage functionalization of pharmaceuticals, natural amino acid modification, and scalable synthesis using a flow-cell electrolyzer. In the future, we plan to expand the substrate scopes of both electrophiles and nucleophiles and further develop the flow-cell electrolyzer technology to achieve optimal reaction efficiency and scalable synthesis. In addition, we will conduct comprehensive experimental and computational studies to gain in-depth mechanistic understandings. This electrochemical C?C cross-coupling paradigm is expected to be highly productive and atomically economic and will find wide-spread applications in developing pharmaceuticals and bioactive molecules. The knowledge gained will have broad impacts on developing other metal based (e.g. Fe, and Co) and even metal free electrochemical C-C, C-N, and C-O, and C-S coupling reactions and other electrochemical organic transformations. In addition, this proposal will provide rich research opportunities for undergraduate students (particularly for Native American undergraduate students) that will enlarge their career vision in health sciences. This AREA grant is essential to the PI’s lab and to providing research and mentoring opportunities for undergraduate and graduate students.
