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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613078
• 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具有键的那些。它们有许多应用，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。该提案的目的是开发使用金属介导的反应合成磷-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片段。由于它们的缺电子和正电荷，膦可以与有机分子进行亲电加成。然而，它们的电子缺陷意味着它们通常不稳定。它们可以使用π供体基团稳定化，但这限制了它们在有机磷合成中的通用性，因为P-结合基团随后被限制为π供体。另一种稳定磷离子的方法是通过金属配位。这不仅使它们稳定，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产生和反应性，以及它们对有机磷合成的适用性。通过从金属配位的氯膦中提取氯离子，将产生金属配位的膦离子。决定磷离子稳定性的因素将通过实验和计算进行评估。使用三氟甲磺酸银生成相应的膦三氟甲磺酸盐络合物。我们已经表明，三氟甲磺酸酯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。磷鎓离子络合物及其三氟甲磺酸酯类似物的反应性将用广泛的有机亲核试剂进行测试，包括芳烃、芳族杂环、烯烃、炔烃和酮。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物。与传统的P-C键形成反应相比，这些亲电加成将提供改进的区域选择性、产率和官能团耐受性，这是由于磷孤对的亲电性和保护增强。金属络合物也可用于模板化反应。配位反应底物顺式的膦配体可以提供额外的控制亲电加成反应的区域选择性，这里描述的方法代表了一个强大的新技术，形成P-C键。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容易性、区域选择性和非常高的官能团耐受性。因此，它们在有机磷化合物的合成中具有广泛的应用前景。