RUI: Synthesis of New P-Metallated Nucleosides

巴克内尔大学的Robert A. Stockland Jr.教授将利用有机金属配合物作为前体，通过磷酸氢（P-H）活化磷酸氢酸盐和相关化合物，合成独特的p金属核苷。这些金属化核苷将作为一种新的无碱交叉偶联反应的转移剂，该反应将用于合成p芳基化衍生物。交叉偶联化学将通过氮、硫和含氧芳香族杂环的结合扩大到包括杂芳基底物。详细的机理研究将阐明关键的反应中间体以及反应的电子和空间范围。此外，通过一种金属中心交换另一种金属中心来合成新的衍生物将被研究，以扩大化学的范围，并纳入在电化学或光物理中具有丰富历史的金属中心。金属化核苷也将被用作合成独特金属有机结构的基石。这项工作将导致新的合成方法的发展，以制备功能化核苷。这些新化合物在医学和化学生物学方面具有潜在的应用价值。此外，这项工作将为合成具有独特几何形状和反应性特征的化合物提供策略，这些化合物是目前方法无法获得的。旨在探索特定结构基序重要性的实验将用于改进合成程序和设计第二代催化剂。参与这些项目的本科生研究人员将在化学的几个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能力。

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.