Chiral Catalysts Designed to Catalyze Organic Reactions

描述（由申请人提供）：该提案描述了小分子手性催化剂的设计和开发，这些催化剂可以产生高活性中间体，并通过非共价相互作用网络使其参与立体选择反应。这项工作的基本原理是一个新的机制框架，其中氢键供体通过抽象和结合弱碱性阴离子离去基来诱导中性底物电离。由此产生的阳离子中间体可以通过静电、氢键和手性离子对内其他弱相互作用的组合诱导进行对映选择反应。阴离子结合催化的概念为阳离子中间体的对映选择性催化反应提供了一种通用的方法，如氧碳离子、铝离子、不稳定碳阳离子、卤离子、芳香杂环阳离子和自由基阳离子。一个至关重要的目标将是回答有关阴离子结合催化的基本机制问题。其中最主要的是对阴离子抽象机制的清晰理解，抽象动力学与所产生的催化剂-阴离子络合物的热力学稳定性之间的关系，以及这两个特征影响对映选择性催化反应结果的方式。从这项工作中得出的机理见解将应用于催化剂控制的糖基化反应，其中通过手性氢键供体催化剂寻求糖源性氧羰基离子添加的非对映选择性。在第二个目标中，通过确定对映选择性、催化单氯化和二氯化反应的方法来解决氯化化合物的立体控制合成。手性氢键给体-氯离子配合物会与高活性的碳阳离子或氯离子中间体结合而产生。这些离子对的崩溃将导致形成所需的对映体富集形式的氯化产物。在第三个目标中，目标将是通过开发一种对映选择性环加成氧化吡啶离子的催化方法，在立体控制反应中产生和参与离域阳离子。第四个目标是寻找控制电子空穴催化反应中对映体选择性的方法。这项工作将包括设计和应用氢键供体催化剂，结合醌衍生物，从而提高其氧化电位。所得到的配合物可以促进有机底物的单电子氧化，并诱导所得到的自由基阳离子中间体的对映选择反应。

DESCRIPTION (provided by applicant): This proposal describes the design and development of small-molecule, chiral catalysts that generate highly reactive intermediates and engage them in stereoselective reactions through networks of non-covalent interactions. The underlying principle in this effort is a new mechanistic framework wherein hydrogen-bond donors induce ionization of neutral substrates by abstracting and binding weakly basic, anionic leaving groups. The resulting cationic intermediate can be induced to undergo enantioselective reactions through a combination of electrostatic, H-bonding, and other weak interactions within the chiral ion pair. The anion binding catalysis concept provides a general approach to enantioselective catalytic reactions of cationic intermediates such as oxocarbenium ions, iminium ions, unstabilized carbocations, halonium ions, aromatic heterocyclic cations, and radical cations. One crucially important aim will be to answer fundamental mechanistic questions relating to anion-binding catalysis. Primary among these are a clear understanding of the mechanism of anion abstraction, the relationship between the kinetics of abstraction and the thermodynamic stability of the resulting catalyst-anion complexes, and the manner in which these two characteristics influence outcomes in enantioselective catalytic reactions. The mechanistic insights drawn from this work will be applied to catalyst-controlled glycosylation reactions, wherein diastereoselectivity in additions to sugar-derived oxocarbenium ions will be sought through the agency of chiral H-bond-donor catalysts. In a second aim, the stereocontrolled synthesis of chlorinated compounds is addressed through the identification of methods for enantioselective, catalytic mono- and di-chlorination reactions. Chiral H-bond donor-chloride complexes will be generated in association with highly reactive carbocationic or chloronium ion intermediates. Collapse of these ion pairs will result in the formation of the desired chlorinated products in enantioenriched form. In a third aim, the goal will be to generate and engage delocalized cations in stereocontrolled reactions, through the development of a catalytic method for enantioselective cycloadditions to oxidopyrylium ions. The fourth aim is directed toward the discovery of methods for controlling enantioselectivity in electron hole-catalyzed reactions. This effort will involve the design and application of H-bond donor catalysts that bind quinone derivatives and thereby increase their oxidation potential. The resulting complex can promote one-electron oxidation of organic substrates, and induce enantioselective reactions of the resulting radical cation intermediates.