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Dannenberg, Steven Gilman

Chemistry

2023

Ph. D.

Metal-catalyzed hydrophosphination is a powerful tool for the synthesis of P-C bond containing compounds due to the ubiquity of alkene substrates and potential for perfect atom economy, or the incorporation of all the atoms in the starting material into the products. Organophosphorus compounds, the products of these reactions, are integral molecules in organic synthesis, catalysis, materials science, and biologically active molecules. However, more widespread use of hydrophosphination is limited because many catalysts are air- and/or water-sensitive, complicated to prepare, or suffer from limited substrate scope or modest activity. Metal-catalyzed hydrophosphination is a powerful tool for the synthesis of P-C bond containing compounds due to the ubiquity of alkene substrates and potential for perfect atom economy, or the incorporation of all the atoms in the starting material into the products. Organophosphorus compounds, the products of these reactions, are integral molecules in organic synthesis, catalysis, materials science, and biologically active molecules. However, more widespread use of hydrophosphination is limited because many catalysts are air- and/or water-sensitive, complicated to prepare, or suffer from limited substrate scope or modest activity. This dissertation aims to address these outstanding challenges for hydrophosphination. We found that commercially available and bench-stable Cu(acac)2 meets many of the criteria for a broadly applicable catalyst. Cu(acac)2 is highly active for the hydrophosphination of alkenes and alkynes at ambient temperature and under 360 nm irradiation. Photocatalytic conditions are critical, and provide high conversions with unactivated substrates, among others. These substrates have never been reported with an air- and water-stable catalyst. The commercial availability, ease of use, and broad substrate scope of Cu(acac)2 make hydrophosphination more available to synthetic chemists. Enhanced reactivity under photolysis is general to copper compounds under irradiation. Several copper salts displayed enhanced reactivity under photolysis, as did an oligomeric copper phosphido compound Cu4([mu]PPh2)4(PtBu3)2, and a monomeric copper phosphido compound IPrCuPPh2. Mechanistic investigations were performed to answer questions about the reactivity of 1, the role of light in catalysis, and to provide direction for further study. A divergent Hammett plot indicated that different mechanisms occur depending on the electron density at the alkene substrate. A radical process was eliminated based on trapping reactions and in situ electron paramagnetic resonance experiments. Isotopic labeling experiments, a zwitterionic trapping experiment, stoichiometric model reactions, and catalytic reactions using proxy intermediates indicated that both the conjugate addition and insertion-based mechanistic pathways occur with this system, depending on the unsaturated substrate. Computational analysis indicated that the lowest energy transition is a ligand-to-metal charge transfer from the phosphido ligand where the lowest occupied molecular orbital (LUMO) has significant Cu-P antibonding character, suggesting that a weakened Cu-P bond accelerates insertion under photocatalytic conditions. This hypothesis explains the greater activity of Cu(acac)2 compared to prior copper-catalyzed hydrophosphination reports and appears to be a general phenomenon for copper(I) catalysts and copper (II) catalysts that are capable of being reduced by phosphine substrate. These results have been leveraged to achieve heretofore unknown catalytic hydrophosphination reactivity, namely the diastereoselective hydrophosphination of a tri-substituted styrene substrate, among other previously unattainable hydrophosphination products. Copper-photocatalyzed hydrophosphination has significantly advanced the scope and activity of hydrophosphination catalysis and copper salts have become the premier catalysts for exploratory hydrophosphination. This dissertation also discusses initial results that suggest the greater potential of copper photocatalysis for hydrophosphination, asymmetric hydrophosphination, hydroarsination and other related reactions. Although these reactions remain a continued challenge, significant groundwork towards their eventual realization has been developed, and suggestions for future work is discussed.