Chiral Complexes Designed to Catalyzed Organic Reactions

该计划致力于开发和阐明立体选择性催化的新原理，以及 在将这些原理应用于手性制备的实用合成方法的发明中， 生物活性化合物。此续订申请侧重于两种不同的生成和 高亲电性中间体的立体控制反应。提出的每个反应流形都是基于 关于从广泛的初步调查中收集的坚定的机械论假说。第一个问题涉及 精确设计的手性脲、硫脲和方酰胺在催化对映体选择性反应中的应用 通过离子对中间体。这些双氢键给体可以提取或结合弱碱性阴离子，例如 卤化物、磺酸盐和羧酸盐，以产生手性离子对，在 随后的前手性阳离子的选择性决定反应。我们发现这两种病毒的结合 氢键给电子体与无手性Lewis或Brnsted酸生成高度活性的络合物，可以 促进弱亲电底物的活化和对映选择性反应。这一新原则是 定向于创造性的新应用，包括从 以及氧杂环己烷的不对称开环。阴离子提取催化原理 还以一种新的方式应用于促进对映体选择性的硼酸盐重排，通过一种新的 涉及对映体离开基团识别的手性识别机制。一种硼酸盐 重排方法论为三取代基的系统构建提供了一种通用的途径 来自现成的有机硼衍生物的立体中心。第二种截然不同的方法涉及 高价碘催化的烯烃氧化氟官能化。我们已经发现，很简单 C2对称的芳基碘多步催化单烯对映选择性二氟化反应 涉及一种高活性的氟烷基碘中间体。这种中间体可以在各种不同的 分子内或分子间反应，导致新的1，1-，1，2-和1，3-氟功能化产物 对映体富集型。努力致力于从机理上阐明新的反应，以及它们的 通过使用实际的氟化物来源实现实际的能力。

This program is dedicated to the development and elucidation of new principles for stereoselective catalysis, and in the application of those principles to the invention of practical synthetic methods for the preparation of chiral, bioactive compounds. This renewal application is focused on two distinct approaches to the generation and stereocontrolled reaction of highly electrophilic intermediates. Each of the proposed reaction manifolds is based on firm mechanistic hypotheses gleaned from extensive preliminary investigations. The first involves the application of precisely designed chiral ureas, thioureas, and squaramides to catalyze enantioselective reactions via ion-pair intermediates. These dual hydrogen-bond donors can abstract or bind weakly basic anions, such as halides, sulfonates, and carboxylates, to generate chiral ion pairs that remain tightly associated during subsequent selectivity-determining reactions of the prochiral cations. We discovered that the combination of hydrogen-bond donors with achiral Lewis or Brønsted acids generates highly reactive complexes that can promote activation and enantioselective reactions of weakly electrophilic substrates. This new principle is directed to creative new applications including the enantioselective multi-component synthesis of amines from carbonyl compounds and to the asymmetric ring opening of oxetanes. The principle of anion-abstraction catalysis is also applied in a new way to the promotion of enantioselective boronate rearrangements, through a novel chiral recognition mechanism involving discrimination of enantiotopic leaving groups. The boronate rearrangement methodology provides a general approach to the systematic construction of trisubstituted stereocenters from readily available organoboron derivatives. The second distinct approach involves the oxidative fluorofunctionalization of alkenes using hypervalent iodine catalysis. We have discovered that simple C2-symmetric aryl iodides catalyze enantioselective difluorination of simple alkenes via a multistep mechanism involving a highly reactive fluoroalkyl iodane intermediate. That intermediate can be intercepted in a variety of intra- or intermolecular reactions, leading to novel, 1,1-, 1,2-, and 1,3-fluorofunctionalized products in highly enantioenriched form. Efforts are directed toward the mechanistic elucidation of the new reactions, and to their practical enablement through the use of practical fluoride sources.