Application of Asymmetric Anion Binding to Palladium-Catalyzed Alkene Functionalization

不对称阴离子结合在钯催化烯烃官能化中的应用

• 批准号: 8836106
• 负责人: Elisabeth Hennessy
• 金额: $ 5.24万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-20 至 2017-01-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8836106
• 关键词: Acetates; Address; Alkenes; Anions; Area; Beryllium; Binding; Biological Assay; Biological Factors; Catalysis; Chemistry; Chloride Ion; Chlorides; Complex; Cyclization; Development; Environment; Equilibrium; Evaluation; Fellowship; Furans; Generations; Geometry; Goals; Hydrogen Bonding; Ions; Laboratories; Ligands; Mediating; Metals; Methodology; Methods; Molecular; Organometallic Chemistry; Oxidants; Palladium; Pharmacologic Substance; Pyrans; Pyrrolidines; Quinones; Reaction; Research; Salts; Sodium Chloride; Solvents; System; Thiourea; Transition Elements; Urea; Variant; abstracting; catalyst; design; empowered; novel strategies; operation; piperidine; public health relevance; pyridine; pyrrolidine

 DESCRIPTION (provided by applicant): The field of enantioselective organometallic chemistry has greatly benefited from the development of chiral ligands that covalently bind transition metal ions to generate an asymmetric environment under which a reaction occurs. Such a strategy, however, is not necessarily compatible with catalysts that require particular coordination geometries, highly electrophilic metal centers, or strong oxidants. As such, the overall goal of the proposed research is to devise an alternative strategy for enantioinduction in organometallic transformations using asymmetric ion-pairing catalysis. Chiral thioureas will be applied as co-catalysts in transformations mediated by transition metal catalysts. Anion abstraction from the transition metal catalyst by the thiourea could generate an asymmetric ion pair intermediate capable of influencing the stereochemical course of the reaction. In order to maximize the level of asymmetry relayed from the chiral hydrogen bond donors to the cationic metal center, catalysts will be evaluated for anion abstraction abilities and non-covalent interactions between the ion pairs. Specifically, the proposed research will apply this strategy to palladium-catalyzed olefin functionalization, a rich area of chemistry that has suffered from a shortage of enantioselective transformations. Established, non-stereoselective variants can generate significant levels of molecular complexity in a single operation. The ability to quickly access a wide range of saturated heterocycles like furans, pyrans, pyrrolidines, and piperidines in a stereocontrolled fashion is particularly appealing. Such structural elements are important components of bioactive natural products and pharmaceuticals and are difficult to synthesize efficiently and asymmetrically via other methods. This proposal seeks to address and achieve the following goals during the fellowship period: (1) Evaluate the ability of achiral and chiral hydrogen bond donors to abstract anions from transition metal salts; and (2) Design and synthesize asymmetric hydrogen bond donor co-catalysts for enantioselective, palladium catalyzed Wacker-type transformations. This represents a new approach to asymmetric palladium(0/II) catalytic transformations and an empowering extension of asymmetric anion binding catalysis. Pairing hydrogen-bond donor catalysis with transition metal catalysis creates a unique opportunity to create an asymmetric metal environment without diminishing, but rather enhancing, the electrophilicity of the metal center.

 描述（由申请人提供）：对映选择性有机金属化学领域极大地受益于手性配体的发展，该手性配体共价结合过渡金属离子以产生发生反应的不对称环境，然而，这种策略不一定兼容。需要特殊配位几何形状、高亲电子金属中心或强氧化剂的催化剂因此，本研究的总体目标是设计一种对映诱导的替代策略。在使用不对称离子对催化的有机金属转化中，手性硫脲将用作过渡金属催化剂介导的转化中的助催化剂，硫脲从过渡金属催化剂中提取阴离子可以产生能够影响立体化学过程的不对称离子对中间体。为了最大化从手性氢键供体传递到阳离子金属中心的不对称水平，将评估催化剂的阴离子。离子对之间的抽象能力和非共价相互作用。 具体来说，拟议的研究将这种策略应用于钯催化的烯烃官能化，这是一个丰富的化学领域，但一直缺乏对映选择性转化，已建立的非立体选择性变体可以在一次操作中产生显着水平的分子复杂性。以立体控制方式快速获得各种饱和杂环（如呋喃、吡喃、吡咯烷和哌啶）的能力特别有吸引力。具有生物活性的天然产物和药物，很难通过其他方法高效、不对称地合成。 该提案旨在在研究金期间解决并实现以下目标：（1）评估非手性和手性氢键供体从过渡金属盐中提取阴离子的能力；（2）设计和合成不对称氢键供体助催化剂用于对映选择性钯催化瓦克型转化 这代表了一种不对称钯 (0/II) 催化转化的新方法以及不对称阴离子结合的增强扩展。将氢键供体催化与过渡金属催化配对创造了一个独特的机会来创建不对称金属环境，而不会减弱而是增强金属中心的亲电性。