Phosphorus-Carbon Bond Formation Using Phosphorus Electrophiles

有机磷化合物被定义为在磷和碳之间有一个键的化合物。它们有许多用途，包括催化配体、抗癌药物和材料。它们形成的关键步骤是磷碳键的形成。本提案的目的是开发利用金属介导反应合成磷碳键的新方法。主要的工具将是一个磷离子，一个带正电的磷碎片和两个连接基团。由于缺电子和带正电荷，磷离子可以与有机分子发生亲电加成反应。然而，它们的电子缺陷意味着它们通常是不稳定的。它们可以使用π给体基团来稳定，但这限制了它们在有机磷合成中的多功能性，因为p结合基团被限制为π给体。稳定磷离子的另一种方法是将它们配位到金属上。这不仅稳定了它们，而且还促进了它们与有机底物的反应。因此，我们将研究过渡金属配位磷离子的生成和反应性，以及它们在有机磷合成中的适用性。金属配位磷离子可以通过从金属配位膦中提取氯、氨基或烷氧基来生成。用三酸银或三酸酐制备相应的三酸膦配合物，该配合物与磷离子处于平衡状态，具有相似的反应活性。磷离子配合物及其三酸盐类似物的反应性将与广泛的有机亲核试剂进行测试，包括芳烃、芳香族杂环、烯烃、炔和酮。由此产生的亲电取代反应将产生新的P-C键，从而产生广泛的有机磷产品，可作为催化、功能材料前体和药物的配体。与传统的P-C键形成反应相比，这些亲电性的添加将提供更好的区域选择性、产率和官能团耐受性，这是由于亲电性的增强和对磷孤对的保护。这里描述的方法代表了形成P-C键的一种强大的新技术。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易于，区域选择性和非常强的官能团耐受性。

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 primary tool will be a phosphenium ion, a positively charged phosphorus fragment with two attached groups. Because of their electron deficiency and positive charge, phosphenium ions can undergo electrophilic addition reactions 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 by coordinating them to metals. Not only does this stabilize them, but it also facilitates their reactions with organic substrates. 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, amino groups or alkoxy groups from metal coordinated phosphines. The corresponding phosphine triflate complexes, which are in equilibrium with phosphenium ions and show similar reactivity, will be generated using silver triflate or triflic anhydride. 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 with applications as ligands for catalysis, functional materials precursors, and pharmaceuticals. 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. 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 with many established P-C bond forming reactions.