Application of Asymmetric Anion Binding to Palladium-Catalyzed Alkene Functionalization

 描述（由申请人提供）：对映选择性有机金属化学领域已经极大地受益于手性配体的开发，所述手性配体共价结合过渡金属离子以产生反应发生的不对称环境。然而，这种策略不一定与需要特定配位几何形状、高度亲电金属中心或强氧化剂的催化剂相容。因此，拟议的研究的总体目标是设计一种替代策略，使用不对称离子配对催化的有机金属转化的对映体诱导。手性硫脲将作为助催化剂应用于过渡金属催化剂介导的转化反应中。硫脲从过渡金属催化剂上夺取阴离子可生成能够影响反应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，将评价催化剂的阴离子提取能力和离子对之间的非共价相互作用。 具体来说，拟议的研究将把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，但缺乏对映选择性转化。已建立的非立体选择性变体可以在单个操作中产生显著水平的分子复杂性。以立体控制的方式快速获得宽范围的饱和杂环如呋喃、吡喃、吡咯烷和哌啶的能力特别吸引人。这些结构元件是生物活性天然产物和药物的重要组分，并且难以通过其他方法有效和不对称地合成。 该提案旨在研究金期间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选择性钯催化Wacker型转化的不对称氢键供体助催化剂。这代表了一种新的方法，不对称钯（0/II）催化转化和授权扩展的不对称阴离子结合催化。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造不对称的金属环境，而不会减少，而是增强金属中心的亲电性。

 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.