C-H Bond Functionalization in Organic Synthesis

有机合成中的C-H键官能化

• 批准号: 7384184
• 负责人: MELANIE S. SANFORD
• 金额: $ 1.41万
• 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 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384184
• 关键词: Acetates; Alkanes; Alkenes; Alkynes; Amides; Amines; Amino Alcohols; Anti-Bacterial Agents; Antioxidants; Biological Factors; Carbon; Condition; Coupling; Cyanides; Cyclization; Development; Diamines; Epothilones; Ethers; Ethyl Ether; Facility Construction Funding Category; Felis catus; Flavonoids; Glycol; Hydrogen Bonding; Iodine; Ketones; Malignant Neoplasms; Methodology; Methods; Mupirocin; Nitrogen; Object Attachment; Operative Surgical Procedures; Organic Synthesis; Oxidants; Oximes; Oxygen; Palladium; Pharmaceutical Preparations; Pharmacologic Substance; Reaction; Reagent; Research; Research Personnel; Route; Scheme; Structure; System; Work; catalyst; functional group; oxidation; programs

This proposal describes the development of general and highly selective Pd-catalyzed methods for converting unactivated arene and alkane C-H bonds to new functional groups X, where X = acetate, ether, amine, halide, cyanide, arene, alkene, or alkyne. These transformationswill find widespread application in SAR studies of pharmaceutical candidates as a result of their generality, functional group tolerance, and extremely high regio- and chemoselectivities. In addition, these methods provide versatile approaches to many other valuable structures, including alpha- and beta-functionalized ketones, 1,2- and 1,3-diols, diamines, and amino alcohols, and oxygen/nitrogen heterocycles, which all serve as important synthetic building blocks. Furthermore, many of these products represent key structural motifs of biologically active molecules, including polyketide natural products such as the epothilones (anti-cancer) and pseudomonic acid (antibacterial) and flavonoid (antibacterial, antioxidant, antimutagenic) derivatives. The proposed research will involve catalytically coupling alkane/arene C-H bond activation at Pd(ll) to subsequent functionalization with hypervalent iodine reagents or other oxidants. High reactivity and regioselectivity will be achieved by the use of organic substrates that contain appropriate chelating functional groups (for example oximes, heterocycles, ethers, amides and amines). The scope and functional group tolerance of these transformations will be explored, and asymmetric catalyst systems will be investigated. In addition, related tandem transformations will be developed in order to use the proposed methodology for the construction of structurally and stereochemically diverse molecules from simple building blocks such as arenes, alkanes, and olefins.

该提案描述了通用和高选择性 Pd 催化方法的开发 将未活化的芳烃和烷烃 C-H 键转化为新的官能团 X，其中 X = 乙酸酯、醚， 胺、卤化物、氰化物、芳烃、烯烃或炔烃。这些转变将在以下领域得到广泛应用： 候选药物的 SAR 研究因其通用性、官能团耐受性和 极高的区域选择性和化学选择性。此外，这些方法还提供了多种方法 许多其他有价值的结构，包括α-和β-官能化酮、1,2-和1,3-二醇， 二胺、氨基醇和氧/氮杂环，它们都是重要的合成化合物 积木。此外，许多这些产品代表了生物活性的关键结构基序 分子，包括聚酮化合物天然产物，例如埃博霉素（抗癌）和假单胞菌 酸（抗菌）和类黄酮（抗菌、抗氧化、抗突变）衍生物。 拟议的研究将涉及催化耦合烷烃/芳烃 C-H 键在 Pd(II) 处的活化 随后用高价碘试剂或其他氧化剂进行官能化。高反应活性和 区域选择性将通过使用含有适当螯合功能的有机底物来实现 基团（例如肟、杂环、醚、酰胺和胺）。范围和职能组 将探索这些转化的耐受性，并将研究不对称催化剂体系。在 此外，还将开发相关的串联转换，以便将拟议的方法用于 从简单的构建块构建结构和立体化学不同的分子，例如 芳烃、烷烃和烯烃。