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）：该提案的总体目标是设计独特的过程，通过 C-C、C-O 和 C-N 键形成，通过 C-H 活化化学进行片段的氧化偶联。催化剂库将被设计用于仿生反应的研究。使用两个指导原则：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 这些库将以高通量微尺度形式部署，以发现迄今为止无法想象的五个领域的反应模式：苯酚偶联、苯胺偶联、烯醇底物与富电子芳族化合物的交叉偶联、烯基苯酚偶联。 ，以及其他偶联/氧化反应，将构建反应“曲线”，并得出有关反应性、选择性和机理的新推论。 该提案的基本特点是能够以有效和合理的方式获取新的反应模式来构建重要的有机结构，从而可以广泛质疑合理的假设并促进优化。新的氧化偶联化学的发展由于步骤数减少和废物流减少而提高了效率，因为反应位点不再需要用官能团预激活以获得选择反应因此，氧化活化的底物数量本质上比非氧化偶联过程的底物数量多，该领域的挑战源于这一事实，即由于典型有机分子中存在大量的 C-H 键，因此任何给定转化的选择性。仿生工艺的使用可以产生具有生物活性的天然产物和类似天然产物的核心，这是药物化学中理想的实体，新的合成方法极大地增加了未开发化学空间的机会，从而产生了造福社会的材料和药物。不在工业环境之外的，将提供给研究生和其他同事。