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（由适用提供）：该提案的总体目的是通过C-H激活化学通过C-C，C-O和C-N键形成片段的氧化耦合来设计独特的过程。催化剂文库将设计用于使用两个指导原理研究仿生反应：1）将催化剂氧化电位与所考虑的底物的氧化电势相匹配，并且2）选择可以利用的金属 氧气再生催化物种。这些库将以高通量显微镜格式部署，以发现迄今为止在五个领域中尚不清楚的反应性模式：苯酚耦合，苯胺耦合，与富含电子芳香族剂的烯醇基质偶联，烷苯基酚酚偶联和其他偶联/氧气的交联。从获得的数据中，将构建反应“轮廓”，有关反应性，选择性和机制的新推断 制作，将通过实验进行测试。该提案的基本标志是能够访问新的反应模式以有效和理性的方式构建重要的有机结构。高吞吐量显微镜实验工具允许广泛审问有理假设，并维持可能的反应空间中许多相互依存变量的优化。新的氧化物耦合化学的发展导致由于较低的步骤计数和较小的废物流而提高效率，因为反应位点不再需要用官能团进行反应以获得选择性反应。因此，氧化激活的底物数量本质上比非氧化耦合过程大。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许多C-H键，在任何给定的转换中都有选择性。使用仿生过程会导致生物活性天然产物和类似天然产物的核心，即医学化学中理想的实体。新的合成方法大大增加了获得未开发的化学空间的机会，从而导致材料和药物使社会受益。在工业环境之外缺席的宝贵培训将为研究生和其他同事提供。