Phosphorus-carbon bond formation using metal coordinated phosphorus electrophiles

使用金属配位磷亲电子试剂形成磷-碳键

• 批准号: RGPIN-2015-04634
• 负责人: Sterenberg, Brian
• 金额: $ 1.46万
• 依托单位: University of Regina
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632645
• 关键词: Phosphorus; carbon; bond; formation; using

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.

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。关键的工具将是一个磷离子，一个带有两个连接基团的阳离子磷碎片。由于缺电子和带正电荷，磷可以通过亲电作用加入到有机分子中。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通过金属配位。这不仅稳定了它们，还增强了它们的亲电性。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。从金属配位的氯化物中提取氯离子，生成金属配位的磷离子。决定磷离子稳定性的因素将通过实验和计算进行评估。用三酸银可生成相应的三酸膦配合物。我们已经证明，三氟酸盐与磷离子处于平衡状态，并以相同的方式反应，但提供更大的官能团耐受性。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、芳烃杂环、烯烃、炔和酮。由此产生的亲电取代反应将产生新的P-C键，从而产生各种有机磷产物。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。金属配合物也可用于模板化反应。反应底物顺式配位到磷配体上可以提供对亲电加成反应区域选择性的额外控制。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。因此，它们将在有机磷化合物的合成中找到许多应用。