Understanding Geometric and Electronic Structure Contributions to Ground and Excited State Cu- and Ni-Catalyzed Cross-Coupling Reactions

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Project Summary Developing sustainable approaches to the synthesis of molecular therapeutics will be important for the continued evolution and success of medicinal and pharmaceutical chemistries. A major component of drug synthesis involves transition metal catalyzed C–X (X = C, N, O, etc.) bond formation reactions. While precious metals such as Pd are used for these reactions, first row transition metals are becoming more widely adopted, as they are abundant and open new mechanistic pathways involving one- and multi-electron transfer reactivity, which can potentially work in concert with ligand noninnocence and multireference electronic structure to form transformative structure/function relationships. The merger of thermal catalysis with photochemistry also provides new mechanistic possibilities for cross-couplings that harness the energy of light to drive bond-formation reactions that would not occur in ground states. However, the nature of inorganic intermediates and the important ultrafast transition metal excited state relaxation processes in ground and excited state cross-coupling reactions are not well understood. This proposal therefore applies physical inorganic approaches to develop a fundamental knowledge base of the geometric and electronic structures of the critical inorganic species formed in Cu- and Ni- catalyzed cross-coupling reactions, as well as the time and energy evolution of photoinduced electronic states involved in excited state catalysis. This knowledge base will ultimately guide the development of a molecular engineering approach to ligand development and catalyst discovery. We will bring new spectroscopic methods to the field, including variable temperature variable field magnetic circular dichroism (VTVH MCD) and X-ray absorption and emission spectroscopies, which will be critical to quantitatively define transition metal electronic structure, including multireference character. Ultrafast optical and X-ray spectroscopic approaches will also be used to define the key photonic energy distribution pathways that define photocatalyst efficiency and further guide ligand perturbations to control the excited state potential energy surfaces (PESs) of photocatalysts. Spectral features of isolable species will be used to experimentally calibrate computational methods to define the critical frontier molecular orbitals and bonding interactions that activate metal centers for reactivity, especially those that are fleeting but critical to catalysis. Electronic structure calculations will also allow for the translation of our understanding of resting states, intermediates, and excited states to reaction coordinates in catalysis and the PESs governing relaxation pathways. In concert with collaborative methodological studies, the proposed research will help inform chemists how to leverage the ground and excited state electronic structures of first-row transition metal complexes and thus guide academic and industry research toward sustainable approaches for bond constructions in drug synthesis.