Phosphorus-carbon bond formation using metal coordinated phosphorus electrophiles

有机磷化合物被定义为那些在磷和碳之间具有键的化合物。它们有许多应用，包括催化、抗癌药物和材料的配体。它们形成的关键步骤是磷-碳键的形成。这项提议的目的是开发利用金属介导的反应来合成磷-碳键的新方法。关键工具将是膦离子，这是一种带有两个连接基团的阳离子磷片段。由于它们的电子缺陷和正电荷，膦可以与有机分子发生亲电加成反应。然而，它们的电子缺乏意味着它们通常是不稳定的。它们可以用pi供体基团稳定，但这限制了它们在有机磷合成中的通用性，因为P-结合基仅限于pi供体。另一种稳定膦离子的方法是通过金属配位。这不仅稳定了它们，而且还增强了它们的亲电性。因此，我们将研究过渡金属配位的膦离子的生成和反应活性，以及它们在有机磷合成中的适用性。金属配位的膦离子是通过从金属配位的氯膦中提取氯而生成的。决定膦离子稳定性的因素将通过实验和计算进行评估。相应的三氟化膦络合物将使用三氟化银生成。我们已经证明，三氟化物与膦离子是平衡的，反应方式相同，但提供了更大的官能团耐受性。将用一系列有机亲核试剂，包括芳烃、芳香族杂环、烯烃、炔烃和酮，测试膦离子络合物及其三氟代类似物的反应性。由此产生的亲电取代反应将导致新的P-C键，从而产生广泛的有机磷产品。与传统的P-C键形成反应相比，这些亲电加成反应将提供更好的区域选择性、产率和官能团耐受性，这是由于增强了亲电性和保护了磷离子对。金属络合物也可用于模板化反应。反应底物顺式配位到膦配体可以提供对亲电加成反应的区域选择性的额外控制。这里描述的方法代表了一种形成P-C键的强大的新技术。与许多已建立的P-C键形成反应相比，金属介导的反应具有独特的简便性、区域选择性和非常高的官能团容忍度。因此，它们将在有机磷化合物的合成中得到广泛的应用。

Organophosphorus compounds are defined as those having a bond between phosphorus and carbon. They have many applications, including ligands for catalysis, anticancer drugs, and materials. The key step in their formation is the creation of the phosphorus-carbon bond. The purpose of this proposal is to develop new methodologies for the synthesis of phosphorus-carbon bonds using metal mediated reactions. The key tool will be a phosphenium ion, a cationic phosphorus fragment with two attached groups. Because of their electron deficiency and positive charge, phosphenium can undergo electrophilic additions to organic molecules. However, their electron deficiency means that they are typically unstable. They can be stablilized using pi donor groups, but this limits their versatility in organophosphorus synthesis because the P-bound groups are then limited to pi donors. An alternative way of stabilizing phosphenium ions is via metal coordination. Not only does this stabilize them, but it also enhances their electrophilicity. We will therefore examine the generation and reactivity of transition metal coordinated phosphenium ions, and their applicability to organophosphorus synthesis. Metal-coordinated phosphenium ions will be generated by abstraction of chloride from metal coordinated chlorophosphines. Factors that determine phosphenium ions stability will be assessed experimentally and computationally. The corresponding phosphine triflate complexes will be generated using silver triflate. We have shown that the triflates are in equilibrium with the phosphenium ions and react in the same way, but provide greater functional group tolerance. The reactivity of the phosphenium ion complexes, and their triflate analogs, will be tested with a wide range of organic nucleophiles, including arenes, aromatic heterocycles, alkenes, alkynes and ketones. The resulting electrophilic substitution reactions will lead to new P-C bonds, resulting in a wide range of organophosphorus products. These electrophilic additions will provide improved regioselectivity, yields, and functional group tolerance compared to traditional P-C bond forming reactions as a result of enhanced electrophilicity and protection of the phosphorus lone pair. Metal complexes can also be used for templated reactions. Coordination of a reactive substrate cis to the phosphenium ligand can provide additional control over the regioselectivity of the electrophilic addition reaction.  The methodologies described here represent a powerful new technique to form P-C bonds. The metal-mediated reactions are uniquely facile, regioselective, and very functional group tolerant compared to many established P-C bond forming reactions. As a result, they will find many applications in the synthesis of organophosphorus compounds.