RUI: Synthesis of New P-Metallated Nucleosides

该奖项由化学合成计划授予小罗伯特·A·斯托克兰教授。将以有机金属络合物为前体，通过磷-氢(P-H)活化磷酸盐和相关化合物合成独特的P-金属核苷。这些金属核苷将在一种新的无碱交叉偶联反应中作为转移剂，该反应将被开发用于合成P-芳基化衍生物。交叉偶联化学将通过引入氮、硫和含氧的芳香族杂环来扩展到包括杂芳基底物。详细的机理研究将揭示关键的反应中间体以及反应的电子和空间范围。此外，还将研究通过一个金属中心交换另一个金属中心来合成新的衍生物，以扩大化学的范围，并纳入在电化学或光物理方面具有丰富历史的金属中心。金属核苷还将被用作合成独特的金属-有机结构的构建块，这项工作将导致制备功能化核苷的新的合成方法的发展。这些新化合物因其在医学和化学生物学中的潜在应用而成为高价值的靶标。此外，这项工作将产生合成具有独特几何结构和反应性轮廓的化合物的策略，这是目前方法无法获得的。将进行旨在探索特定结构基序重要性的实验，以完善合成程序并设计第二代催化剂。参与这些项目的本科生研究人员将在几个化学领域获得宝贵的实验室经验，并将磨练他们的批判性思维和解决问题的技能。

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.