Phosphorus-Carbon Bond Formation Using Phosphorus Electrophiles

使用磷亲电子试剂形成磷-碳键

• 批准号: RGPIN-2021-02522
• 负责人: Sterenberg, Brian
• 金额: $ 1.75万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742029
• 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 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.

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。主要的工具将是膦离子，一种带有两个连接基团的带正电的磷片段。由于它们的电子缺陷和正电荷，膦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将它们与金属配位。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膦中提取氯化物、氨基或烷氧基而生成的。相应的三氟化膦络合物与膦离子处于平衡状态，并显示出类似的反应活性，将使用三氟化银或三氟酸酐生成。将用包括芳烃、芳香族杂环、烯烃、炔烃和酮在内的多种有机亲核试剂来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，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。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。