C-H Bond Functionalization in Organic Synthesis

有机合成中的C-H键官能化

• 批准号: 8299468
• 负责人: MELANIE S. SANFORD
• 金额: $ 27.36万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8299468
• 关键词: Address; Aerobic; Air; Alkanes; Area; Benign; Biological; Biological Availability; Biological Factors; Biological Products; Carbon; Catalysis; Development; Dioxygen; Drug Delivery Systems; Environment; Fluorides; Fluorine; Goals; Health; Human; Hydrogen Bonding; Image; Investigation; Iodine; Kinetics; Ligands; Metabolic; Metals; Methods; Modification; Organic Synthesis; Oxidants; Oxidation-Reduction; Palladium; Pharmaceutical Chemistry; Pharmacologic Substance; Positron-Emission Tomography; Process; Reaction; Reagent; Research; Route; Source; Staging; Structure; Therapeutic Agents; Work; catalyst; chemical reaction; design; functional group; human disease; inorganic phosphate; novel; oxidation; scaffold; trifluoromethyl group

DESCRIPTION (provided by applicant): This proposal describes the development of general and selective Pd-catalyzed methods for the ligand-directed conversion of unactivated arene and alkane carbon-hydrogen bonds into new functional groups. Aims 1 and 2 focus on exploring new methods for C-H bond fluorination and trifluoromethylation, utilizing readily available and inexpensive fluoride and trifluoromethyl starting materials. A key objective is to identify novel (and potentially broadly applicable) reactivity modes for the Pd-catalyzed introduction of fluorinated groups into organic molecules. Aim 3 seeks to develop methods that use readily available dioxygen as the terminal oxidant for converting C-H bonds into diverse functional groups. Aim 4 focuses on developing widely applicable asymmetric catalytic C-H functionalization reactions. All of these aims will be tackled by taking advantage of the Sanford group's expertise in new reaction development/optimization, in detailed mechanistic investigations, and in the synthesis/characterization of reactive organopalladium intermediates. The reactions developed herein will find application in the synthesis/diversification of pharmaceutical candidates, natural products, positron emission tomography (PET) imaging agents, and biological probes.

描述（由申请人提供）：该提案描述了用于将未活化的芳烃和烷烃碳-氢键配体导向转化为新官能团的一般和选择性Pd催化方法的开发。目标1和2集中于探索C-H键取代和三氟甲基化的新方法，利用容易获得且廉价的氟化物和三氟甲基起始原料。一个关键的目标是确定新的（和潜在的广泛适用的）Pd催化引入氟化基团的有机分子的反应模式。目标3寻求开发使用容易获得的分子氧作为末端氧化剂将C-H键转化为不同官能团的方法。目标4是发展具有广泛应用前景的不对称催化C-H官能化反应。所有这些目标都将通过利用Sanford集团在新反应开发/优化，详细的机理研究以及反应性有机钯中间体的合成/表征方面的专业知识来解决。本文开发的反应将应用于药物候选物、天然产物、正电子发射断层扫描（PET）成像剂和生物探针的合成/多样化。