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）：该提案描述了将一般和选择性PD催化的方法开发，用于将未激活的Arene和烷烃碳氧键转化为新功能组的配体定向转化。目标1和2专注于探索用于C-H键氟化和三氟甲基化的新方法，利用易于使用的氟化物和三氟甲基的起始材料。一个关键目的是确定PD催化基团在有机分子中引入PD催化基团的新颖（可能广泛适用）反应性模式。 AIM 3旨在开发使用易于使用的二氧化物作为将C-H键转换为多种官能团的末端氧化剂的方法。 AIM 4专注于开发广泛适用的不对称催化C-H功能化反应。所有这些目标都将通过利用桑福德集团在新的反应开发/优化，详细的机械研究以及反应性有机甲基中间体的综合/表征方面的专业知识来解决。本文所开发的反应将在药物候选，天然产物，正电子发射断层扫描（PET）成像剂和生物学探针的合成/多样化中找到应用。