Catalytic Oxidative Fragment Coupling Reactions

催化氧化片段偶联反应

• 批准号: 9293348
• 负责人: Marisa C Kozlowski
• 金额: $ 29.56万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9293348
• 关键词: Acids; Alkanes; Amination; Amines; Aniline; Area; Benign; Biological; Biomimetics; Catalysis; Chemicals; Chemistry; Coupled; Coupling; Data; Development; Diabetes Mellitus; Dioxygen; Drug Industry; Electrons; Eugenol; Felis catus; Goals; Grant; Homo; Hydrogen Bonding; Hydroxyl Radical; Imines; Indoles; Industrialization; Ketones; Libraries; Metals; Methods; Naphthols; Natural Products; Natural regeneration; Organic Synthesis; Oxidants; Oxidases; Oxygen; Oxygenases; Pattern; Pharmaceutical Chemistry; Pharmacologic Substance; Phenols; Process; Pyrroles; Reaction; Research; Resources; Site; Societies; Stream; Structure; Testing; Training; Water; Work; bioactive natural products; c new; catalyst; cost; design; functional group; graduate student; innovation; oxidation; programs; public health relevance; small molecule; therapeutic target; tool; trend; wasting

 DESCRIPTION (provided by applicant): The overall objective of this proposal is to devise unique processes for the oxidative coupling of fragments via C-C, C-O, and C-N bond formation by means of C-H activation chemistry. Catalyst libraries will be designed for study of biomimetic reactions using the two guiding principles: 1) matching catalyst oxidation potentials with the oxidation potentials of the substrates under consideration and 2) selecting metals that can utilize oxygen to regenerate the catalytic species. These libraries will be deployed in a high-throughput microscale format to discover reactivity patterns heretofore unimagined in five areas: phenol coupling, aniline coupling, cross-coupling of enolic substrates with electron-rich aromatics, alkenyl phenol coupling, and other couplings/oxygenations. From the data obtained, reaction "profiles" will be constructed and new inferences about reactivity, selectivity, and mechanism will be made, which will be tested experimentally. The fundamental hallmark of this proposal is the ability to access new reaction patterns to construct important organic structures in an efficient and rational manner. High throughput microscale experimentation tools permit rational hypotheses to be interrogated broadly and facilitate optimization of the many interdependent variables in the possible reaction space. The development of new oxidative coupling chemistry leads to increases in efficiency due to lower step counts and smaller waste streams, because reaction sites no longer need to be preactivated with functional groups in order to obtain a selective reaction. As a consequence, the number of substrates for oxidative activation is intrinsically larger than for non-oxidative coupling processes. The challenge in this area follows from this fact, namely selectivity in any given transformation due the numerous C-H bonds present in a typical organic molecule. Use of biomimetic processes leads to bioactive natural products and natural product-like cores, desirable entities in medicinal chemistry. New synthetic methods greatly increase access to untapped chemical space, leading to materials and pharmaceuticals that benefit society. Invaluable training, absent outside of industrial settings, will be afforded to graduate students and other coworkers.

 描述(由申请人提供)：本提案的总体目标是通过C-H活化化学方法设计通过C-C、C-O和C-N键形成的片段氧化偶联的独特过程。将根据两个指导原则设计用于仿生反应研究的催化剂库：1)将催化剂氧化电位与所考虑的底物的氧化电位相匹配；2)选择可以利用的金属 氧气，以再生催化物种。这些文库将以高通量的微尺度格式部署，以在五个领域发现迄今无法想象的反应模式：苯酚偶联、苯胺偶联、烯烃底物与富含电子的芳烃的交叉偶联、烯基苯酚偶联和其他偶联/氧化反应。根据所获得的数据，将建立反应“轮廓”，并将对反应性、选择性和机理作出新的推断。 将在实验中进行测试。这一提议的基本标志是能够以有效和合理的方式获得新的反应模式来构建重要的有机结构。高通量的微型实验工具允许合理的假设被广泛询问，并有助于在可能的反应空间中优化许多相互依赖的变量。新的氧化偶联化学的发展提高了效率，因为步骤数更少，废流更少，因为反应部位不再需要用官能团预活化来获得选择性反应。因此，氧化活化的底物数量本质上大于非氧化偶联过程的底物数量。这一领域的挑战源于这一事实，即由于典型的有机分子中存在大量的C-H键，在任何给定的转化中都具有选择性。仿生过程的使用导致了生物活性的天然产物和天然产物样的核心，在药物化学中是理想的实体。新的合成方法极大地增加了进入未开发的化学空间的机会，导致了造福社会的材料和药品。将为研究生和其他同事提供无价的培训，这些培训在工业环境之外是不存在的。