RUI: Synthesis of New P-Metallated Nucleosides

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With this award from the Chemical Synthesis Program, Prof. Robert A. Stockland Jr. from Bucknell University will synthesize unique P-metallated nucleosides through phosphorus-hydrogen (P-H) activation of hydrogen phosphonates and related compounds using organometallic complexes as precursors. These metallated nucleosides will serve as transfer agents in a new base-free cross-coupling reaction that will be developed for the synthesis of P-arylated derivatives. The cross-coupling chemistry will be expanded to include heteroaryl substrates through the incorporation of nitrogen, sulfur, and oxygen-containing aromatic heterocycles. Detailed mechanistic studies will shed light on key reaction intermediates as well as the electronic and steric scope of the reaction. Furthermore, the synthesis of new derivatives through the exchange of one metal center for another will be investigated in order to expand the scope of the chemistry and incorporate metal centers that have a rich history in electrochemistry or photophysics. The metallated nucleosides will also be used as building blocks in the synthesis of unique metal-organic architectures.This work will lead to the development of new synthetic methodology for the preparation of functionalized nucleosides. These new compounds are high-value targets due to their potential applications in medicine and chemical biology. Furthermore, this work will generate strategies for the synthesis of compounds with unique geometries and reactivity profiles that are not accessible with current methods. Experiments designed to probe the importance of specific structural motifs will be carried out to refine the synthetic procedures and design second-generation catalysts. The undergraduate researchers involved in these projects will gain valuable laboratory experience in several areas of chemistry and will hone their critical thinking and problem solving skills.