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针对一类新的“C-H官能化”反应，涉及Pd催化的脂肪族碳-碳单键脱氢以形成芳族、杂芳族和烯烃产物。这些反应在药物和生物活性分子的合成中具有广泛的用途。这种新的反应性将建立在有氧氧化催化的最新进展，使分子氧作为化学计量的氧化剂/氢受体，形成水作为反应的唯一副产物。针对新的Pd催化剂的开发和其合成应用的调查的实证研究将通过系统的机理研究来补充，以建立有助于成功反应的基本原则。针对四种不同类型的反应：（1）环己酮和环己烯酮脱氢制备各种取代苯酚衍生物，（2）酮和其它羰基化合物脱氢制备通用的1，2-不饱和羰基化合物，（3）环己烯脱氢制备各种取代芳烃，和（4）六元氮杂环脱氢制备喹啉和吡啶衍生物。用于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，所述合成路线包括Diels-Alder环加成、罗宾逊环化和简单的缩合和加成反应。 这些脱氢反应中的关键步骤包括Pd II介导的C-H键的活化，通常来自相对活化的位点（例如，与羰基相邻或在烯丙基位置），以形成PdII-烷基中间体，然后进行2-氢化物消除以产生不饱和产物和PdII-氢化物中间体。通过分子氧氧化PdII-H物质使活性PdII催化剂再生。新的配体的Pd催化剂的识别将发挥重要作用，在这项工作中，因为配体是至关重要的调节PdII的反应中涉及的有机基质和稳定的还原形式的Pd（Pd 0和PdII-H）的催化剂再氧化过程中的反应。总的来说，开发有效的新催化剂用于C-C键的有氧脱氢，以及容易合成这些反应的各种有机底物，将提供环境友好的路线，以选择性取代的芳族和杂芳族化合物，其竞争或超过有机化学中一些最强大的合成转化，如金属催化的交叉偶联反应。