Chiral Complexes Designed to Catalyzed Organic Reactions

该计划致力于发展和阐明立体选择性催化的新原理， 在将这些原理应用于制备手性化合物的实用合成方法的发明中， 生物活性化合物此更新应用程序的重点是两种不同的方法来生成， 高度亲电中间体的立体控制反应。每个建议的反应歧管是基于 从广泛的初步调查中收集到的可靠的机械假说。第一个涉及 精确设计的手性脲、硫脲和方酰胺在催化对映选择性反应中的应用 通过离子对中间体。这些双氢键供体可以提取或结合弱碱性阴离子，如 卤化物，磺酸盐和羧酸盐，以产生手性离子对，这些离子对在使用过程中保持紧密缔合。 随后的前手性阳离子的选择性决定反应。我们发现， 氢键供体与非手性刘易斯酸或布朗斯台德酸产生高度反应性的络合物， 促进弱亲电底物的活化和对映选择性反应。这一新原则是 本发明涉及创造性的新应用， 羰基化合物和氧杂环丁烷的不对称开环。阴离子萃取催化原理 也以新的方式应用于促进对映选择性硼酸酯重排，通过一种新的 手性识别机制涉及对映体离去基团的歧视。硼酸酯 重排方法提供了一种系统构建三取代 来自容易获得的有机硼衍生物的立构中心。第二种不同的方法涉及 使用高价碘催化的烯烃的氧化氟官能化。我们发现， C2-对称芳基碘催化简单烯烃的不对称二取代反应 涉及高反应性氟烷基碘烷中间体。这种中间体可以通过多种方式被拦截， 分子内或分子间的反应，导致新的，1，1-，1，2-和1，3-氟官能化的产物， 对映体富集形式。努力的方向是对新反应的机理阐明，并对它们的反应机理进行研究。 通过使用实际的氟化物源来实现。

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.