Chiral Catalysts Designed to Catalyze Organic Reactions

描述（由申请人提供）：本提案描述了小分子手性催化剂的设计和开发，该催化剂可生成高活性中间体，并通过非共价相互作用网络使其参与立体选择性反应。这项工作的基本原理是一个新的机制框架，其中氢键供体诱导中性底物的离子化，通过提取和结合弱碱性，阴离子离去基团。所得的阳离子中间体可以通过手性离子对内的静电、H-键合和其他弱相互作用的组合而被诱导经历对映选择性反应。阴离子结合催化概念提供了阳离子中间体如氧代碳鎓离子、亚胺鎓离子、不稳定碳阳离子、卤鎓离子、芳族杂环阳离子和自由基阳离子的对映选择性催化反应的一般方法。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械问题。其中主要是一个清晰的理解的机制，阴离子抽象，抽象的动力学和热力学稳定性的催化剂-阴离子络合物之间的关系，以及这两个特点的方式影响结果在对映选择性催化反应。从这项工作中得出的机理的见解将被应用到催化剂控制的糖基化反应，其中在除了糖衍生的oxocarbenium离子的非对映选择性将寻求通过机构的手性H-键供体催化剂。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H-键供体-氯络合物将与高活性碳阳离子或氯离子中间体结合产生。这些离子对的崩溃将导致形成对映体富集形式的所需氯化产物。在第三个目标中，目标将是通过开发对映选择性环加成到oxidopyrylium离子的催化方法，在立体控制反应中产生并接合离域阳离子。第四个目标是发现控制电子空穴催化反应中对映体选择性的方法。这项工作将涉及氢键供体催化剂的设计和应用，结合醌衍生物，从而提高其氧化电位。所得配合物可促进有机底物的单电子氧化，并诱导所得自由基阳离子中间体的对映选择性反应。

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.