Palladium-Catalyzed Aerobic Dehydrogenation of Carbon-Carbon Bonds

钯催化碳-碳键有氧脱氢

• 批准号: 8449250
• 负责人: Shannon S Stahl
• 金额: $ 26.71万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8449250
• 关键词: Address; Aerobic; Aldehydes; Alder plant; Alkenes; Amides; Benign; Carbon; Catalysis; Complement; Coupling; Cyclohexanones; Development; Diels Alder reaction; Esters; Family; Hydrogen; Hydrogen Bonding; Investigation; Ketones; Lead; Ligands; Mediating; Metals; Methods; Molecular; Natural regeneration; Nitrogen; Organic Chemistry; Organic Synthesis; Oxidants; Oxygen; Palladium; Pattern; Pharmacologic Substance; Phenols; Physical condensation; Play; Positioning Attribute; Preparation; Process; Production; Reaction; Research; Role; Route; Site; Solvents; Structure; System; Therapeutic Agents; Water; Work; carbonyl compound; carbonyl group; catalyst; cycloaddition; cyclohexene; dehydrogenation; novel; oxidation; pyridine; quinoline; single bond

DESCRIPTION (provided by applicant): The research outlined in this proposal targets a new class of "C-H functionalization" reactions, involving Pd-catalyzed dehydrogenation of aliphatic carbon-carbon single bonds to form aromatic, heteroaromatic and alkene products. These reactions should have widespread utility in the synthesis of pharmaceuticals and biologically active molecules. This novel reactivity will build upon recent advances in aerobic oxidation catalysis to enable molecular oxygen to serve as the stoichiometric oxidant/hydrogen acceptor, forming of water as the sole byproduct of the reaction. Empirical studies directed toward the development of new Pd catalysts and investigation of their synthetic applications will be complemented by systematic mechanistic studies to establish the fundamental principles that contribute to successful reactivity. Four different classes of reactions are targeted: (1) dehydrogenation of cyclohexanones and cyclohexenones to prepare a variety of substituted phenol derivatives, (2) dehydrogenation of ketones and other carbonyl compounds to prepare versatile 1,2-unsaturated carbonyl compounds, (3) dehydrogenation of cyclohexenes to prepare a variety of substituted arenes, and (4) dehydrogenation of 6-membered nitrogen heterocycles to prepare quinoline and pyridine derivatives. Substrates for these reactions can be obtained from readily available starting materials via a number of versatile synthetic routes, including Diels-Alder cycloadditions, Robinson annulations, and simple condensation and addition reactions. Key steps in these dehydrogenation reactions include PdII-mediated activation of a C-H bond, often from a relatively activated site (e.g., adjacent to a carbonyl group or in an allylic position), to form a PdII- alkyl intermediate, followed by 2-hydride elimination to produce the unsaturated product and a PdII-hydride intermediate. Oxidation of the PdII-H species by molecular oxygen regenerates the active PdII catalyst. The identification of new ligands for the Pd catalysts will play an important role in this work because the ligands are critical to modulate the reactivity of PdII in the reactions involving the organic substrate and to stabilize the reduced forms of Pd (Pd0 and PdII-H) in the catalyst reoxidation process. Overall, the development of efficient new catalysts for aerobic dehydrogenation of C-C bonds, together with the ease of synthetic access to diverse organic substrates for these reactions, will provide environmentally benign routes to selectively substituted aromatic and heteroaromatic compounds that rival or surpass the utility of some of the most powerful synthetic transformations in organic chemistry, such as metal-catalyzed cross-coupling reactions.

描述（由申请人提供）：本提案中概述的研究目标是一类新型“C-H官能化”反应，涉及钯催化脂肪族碳-碳单键脱氢形成芳香族、杂芳香族和烯烃产物。这些反应应该在药物和生物活性分子的合成中具有广泛的用途。这种新颖的反应性将建立在有氧氧化催化的最新进展的基础上，使分子氧能够充当化学计量的氧化剂/氢受体，形成水作为反应的唯一副产物。针对新型钯催化剂开发及其合成应用研究的实证研究将得到系统机理研究的补充，以建立有助于成功反应的基本原理。目标是四类不同的反应：（1）环己酮和环己烯酮脱氢以制备各种取代的苯酚衍生物，（2）酮和其他羰基化合物脱氢以制备通用的1,2-不饱和羰基化合物，（3）环己烯脱氢以制备各种取代的芳烃，以及 (4)六元氮杂环脱氢制备喹啉和吡啶衍生物。这些反应的底物可以通过许多通用的合成路线从容易获得的起始材料获得，包括狄尔斯-阿尔德环加成、罗宾逊成环以及简单的缩合和加成反应。 这些脱氢反应中的关键步骤包括 PdII 介导的 C-H 键活化，通常从相对活化的位点（例如，邻近羰基或烯丙基位置），形成 PdII-烷基中间体，然后进行 2-氢化物消除，产生不饱和产物和 PdII-氢化物中间体。 PdII-H 物质被分子氧氧化，可再生活性 PdII 催化剂。 Pd 催化剂新配体的识别将在这项工作中发挥重要作用，因为配体对于调节 PdII 在涉及有机底物的反应中的反应性以及在催化剂再氧化过程中稳定 Pd 的还原形式（Pd0 和 PdII-H）至关重要。总体而言，开发用于 C-C 键有氧脱氢的高效新型催化剂，以及易于合成这些反应的各种有机底物，将为选择性取代的芳香族和杂芳香族化合物提供环境友好的途径，这些化合物可与有机化学中一些最强大的合成转化（例如金属催化的交叉偶联反应）相媲美或超越。