C-H Bond Functionalization in Organic Synthesis

有机合成中的C-H键官能化

• 批准号: 7933118
• 负责人: MELANIE S. SANFORD
• 金额: $ 13.03万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7933118
• 关键词: Acetates; Alkanes; Alkenes; Alkynes; Amides; Amines; Amino Alcohols; Anti-Bacterial Agents; Antioxidants; Biological Factors; Carbon; Coupling; Cyanides; Cyclization; Development; Diamines; Epothilones; Ethers; Felis catus; Flavonoids; Glycols; Hydrogen Bonding; Iodine; Ketones; Malignant Neoplasms; Methodology; Methods; Mupirocin; Nitrogen; Operative Surgical Procedures; Organic Synthesis; Oxidants; Oximes; Oxygen; Palladium; Pharmacologic Substance; Reaction; Reagent; Research; Research Personnel; Route; Scheme; Structure; System; Work; catalyst; drug candidate; functional group; oxidation; programs

DESCRIPTION (provided by applicant): 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 transformations will 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.

描述（由申请人提供）：本提案描述了将未活化的芳烃和烷烃C-H键转化为新官能团X的一般和高选择性Pd催化方法的开发，其中X =乙酸酯、醚、胺、卤化物、氰化物、芳烃、烯烃或炔烃。这些转换将发现广泛的应用在SAR研究的药物候选人，由于其一般性，官能团的耐受性，以及极高的区域和化学选择性。此外，这些方法为许多其他有价值的结构提供了通用的方法，包括α-和β-官能化的酮、1，2-和1，3-二醇、二胺和氨基醇以及氧/氮杂环，它们都是重要的合成结构单元。此外，许多这些产品代表了生物活性分子的关键结构基序，包括聚酮化合物天然产品，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。所提出的研究将涉及在Pd（II）处催化偶联烷烃/芳烃C-H键活化以随后用高价碘试剂或其他氧化剂官能化。通过使用含有适当螯合官能团（例如肟、杂环、醚、酰胺和胺）的有机底物将实现高反应性和区域选择性。这些转换的范围和官能团的宽容将被探索，和不对称催化剂系统将被调查。此外，将开发相关的串联转换，以使用所提出的方法，从简单的积木，如芳烃，烷烃和烯烃的结构和立体化学不同的分子的建设。