Synthetic Methods based on Biphilic Phosphorus Catalysts

基于双亲磷催化剂的合成方法

• 批准号: 10092173
• 负责人: ALEXANDER T RADOSEVICH
• 金额: $ 41.31万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092173
• 关键词: Alkenes; Amaze; Amides; Amidines; Aromatic Amines; Carbon; Catalysis; Chemistry; Complex; Coupling; Cyclization; Dehydration; Development; Electrons; Elements; Funding; Future; Geometry; Goals; Guanidines; Health; Human; Ice; Ketones; Laboratories; Ligands; Lytic; Metals; Methods; Modality; Molecular Weight; Nitrogen; Organic Synthesis; Outcome; Oxidation-Reduction; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Phosphines; Phosphorus; Play; Protocols documentation; Reaction; Reducing Agents; Research; Role; Route; Science; Shapes; Shunt Device; Structure; Technology; Transition Elements; Urea; base; catalyst; chemical synthesis; cost; design; drug candidate; drug synthesis; foot; human disease; improved; indoline; innovation; insight; nitrene; novel; oxidation; small molecule

PROJECT SUMMARY/ABSTRACT Advances in catalytic science and technology enable the preparation of pharmaceutical agents used to treat human disease. This project has the long-term goal of developing a broad class of inexpensive nonmetal catalysts that promote catalytic transformations via formal oxidation state cycling in qualitative analogy to transition metal catalysis. Within this overarching goal, the primary focus of this proposal is the design and application of phosphorus-based catalysts that function in the P(III)⇌P(V) redox couple. While phosphines are well-established in catalysis as spectator ligands for transition metal catalysis and as nucleophilic catalysts, this research describes innovative phosphorus-based catalysts of novel com- position and structure that explore the structural and electronic conditions required to enable new catalyt- ically-relevant reactivity via reversible P(III)⇌P(V) oxidation state cycling. The first major effort is the de- velopment of phosphine-catalyzed O-atom transfer methods that result in reductive functionalization of nitroarene compounds through the formation of new carbon-nitrogen bonds. The second major effort is the development of net redox-neutral (cyclo)dehydration reactions that are accomplished by phosphine catalysis in the P(III)⇌P(V) redox couple. The proposed research is expected to yield new practical cata- lytic methods for the construction of pharmacologically-relevant small molecules that meet the challenges of sustainable synthesis, and an improved fundamental understanding the interplay between structure and reactivity in the p-block that will underpin future development of nonmetals for atom transfer, bond activation, and catalysis. Taken together, these outcomes will advance nonmetal-based redox catalysis as a new and powerful modality in pharmaceutical synthesis.

项目摘要/摘要 催化科学和技术的进步使制剂可以制备过去 治疗人类疾病。该项目的长期目标是开发一系列廉价的一类 通过正式氧化状态循环在定性中促进催化转化的非金属催化剂 类似于过渡金属催化。在这个总体目标中，该提案的主要重点是 基于磷的催化剂的设计和应用，在P（iii）⇌P（v）氧化还原夫妇中起作用。 而磷在催化中是众所周知的，作为过渡金属催化和的观众配体 作为核螺旋催化剂，这项研究描述了基于创新的磷的新型催化剂 位置和结构，探索使新催化作用所需的结构和电子条件 通过可逆P（III）⇌P（V）氧化态循环的反应性。第一个主要努力是 磷酸催化的O-ATOM转移方法的速度导致降低的功能化 硝化化合物通过形成新的碳氮键。第二个主要努力是 磷酸实现的净氧化还原（环）脱水反应的发展 p（iii）⇌P（v）氧化还原夫妇中的催化。拟议的研究预计将产生新的实用cata- 构建与挑战相关的小分子的溶血方法 可持续合成，以及基本了解结构之间的相互作用 P块中的反应性将在未来的原子转移，键的非金属发展基础上发展 激活和催化。综上所述，这些结果将推进非金属的氧化还原催化 作为药物合成的新型和强大的方式。