Synthetic Methods based on Biphilic Phosphorus Catalysts

基于双亲磷催化剂的合成方法

• 批准号: 10573202
• 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/10573202
• 关键词: Acylation; Alkenes; Amaze; Amides; Amidines; Aromatic Amines; Carbon; Catalysis; Chemistry; Complex; Coupling; Cyclization; Dehydration; Development; Electronics; Electrons; Elements; Funding; Future; Geometry; Goals; Guanidines; Health; Human; Ketones; Laboratories; Ligands; Metals; Methods; Modality; Molecular Weight; Nitrogen; Organic Synthesis; Outcome; Oxidation-Reduction; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phosphines; Phosphorus; Play; Protocols documentation; Reaction; Reducing Agents; Research; Role; Route; Science; Shapes; Shunt Device; Structure; Technology; Transition Elements; Urea; catalyst; chemical synthesis; cost; design; drug candidate; drug synthesis; foot; human disease; improved; indoline; innovation; insight; manufacture; nitrene; novel; oxidation; pharmacologic; 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备用于 治疗人类疾病。这个项目的长期目标是开发一大批廉价的 通过定性的形式氧化态循环促进催化转化的非金属催化剂 类似于过渡金属催化。在这一总体目标内，这项提案的主要重点是 P(III)-⇌-P(V)氧化还原电偶中磷基催化剂的设计与应用。 虽然膦作为过渡金属催化的旁观者配体在催化中得到了很好的应用 作为亲核催化剂，本研究介绍了一种新型的组合物磷基催化剂。 探索实现新催化剂所需的结构和电子条件的位置和结构- 通过可逆P(III)⇌P(V)氧化态循环的相关反应性。第一个主要努力是去... 膦催化的氧原子转移方法的研究进展 硝基芳烃化合物通过形成新的碳氮键。第二项主要工作是 磷化氢完成的净氧化还原中性(环)脱水反应的研究进展 P(III)-⇌-P(V)氧化还原对的催化作用预计拟议的研究将产生新的实用目录- 构建迎接挑战的药理相关小分子的裂解方法 可持续的综合，以及对结构之间相互作用的更好的基本理解 以及p-基团的反应性，这将为非金属的未来发展奠定基础，用于原子转移、键 激活和催化。综上所述，这些成果将推进非金属基氧化还原催化。 作为一种新的、功能强大的药物合成方法。