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(申请人提供)：手性配体的发展极大地促进了对映体选择性有机金属化学领域的发展，手性配体可以共价结合过渡金属离子以产生不对称的环境，在这种环境下发生反应。然而，这种策略不一定与需要特殊配位几何结构、高度亲电的金属中心或强氧化剂的催化剂兼容。因此，拟议研究的总体目标是设计一种使用不对称离子对催化在有机金属转化中诱导对映体的替代策略。手性硫脲类化合物将作为助催化剂应用于过渡金属催化转化反应中。硫脲可以从过渡金属催化剂中提取阴离子，生成不对称离子对中间体，能够影响反应的立体化学过程。为了最大化从手性氢键给体传递到阳离子金属中心的不对称程度，催化剂将被评估阴离子提取能力和离子对之间的非共价相互作用。 具体地说，拟议的研究将把这一策略应用于钯催化的烯烃功能化，这是一个丰富的化学领域，但缺乏对映选择性转化。已建立的非立体选择性变异可以在一次操作中产生显著水平的分子复杂性。能够以立体控制的方式快速获得广泛的饱和杂环，如呋喃、吡喃、吡咯烷和哌啶，这一能力特别吸引人。这类结构元素是生物活性天然产物和药物的重要组成部分，很难通过其他方法进行有效和不对称的合成。 这项建议旨在解决和实现以下目标：(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)设计和合成用于对映体选择性的不对称氢键供体共催化剂，钯催化的Wacker类型转化。这代表了一种不对称钯(0/II)催化转化的新方法，也是不对称阴离子结合催化的有力扩展。将氢键给体催化与过渡金属催化配对，创造了一个独特的机会来创造不对称的金属环境，而不会减少金属中心的亲电性，而是增强了金属中心的亲电性。