Chiral Complexes Designed to Catalyzed Organic Reactions

设计用于催化有机反应的手性配合物

• 批准号: 10393975
• 负责人: ERIC N JACOBSEN
• 金额: $ 0.9万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10393975
• 关键词: Acids; Alkanesulfonates; Alkenes; Anions; Binding; Catalysis; Cations; Complex; Development; Discrimination; Fluorides; Fruit; Generations; Glean; Hydrogen Bonding; Intercept; Investigation; Iodides; Iodine; Ions; Methodology; Methods; Preparation; Reaction; Source; Structure; Thiourea; Transition Elements; Urea; base; carboxylate; catalyst; design; invention; metal complex; novel; programs; small molecule

PROJECT SUMMARY/ABSTRACT 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 (HBDs) 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 HBDs 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 developed here specifically in the context of cooperative reactions between achiral transition metal complexes and chiral HBDs. 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.

项目总结/摘要 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（HBDs）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， 随后的前手性阳离子的选择性决定反应。我们发现， HBD与非手性刘易斯酸或布朗斯台德酸产生高度反应性的复合物，可以促进活化， 弱亲电底物的对映选择性反应。这一新的原则是在这里专门制定的， 非手性过渡金属配合物与手性HBDs之间的协同反应。原则 阴离子萃取催化的新方法也被应用于对映选择性硼酸酯的合成 重排，通过一种新的手性识别机制，涉及歧视对映体离开 组硼酸酯重排方法提供了一个系统的建设的一般途径 三取代的立体中心从容易获得的有机硼衍生物。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。我们已经发现 简单C2-对称芳基碘通过多步催化简单烯烃的对映选择性二取代反应， 涉及高反应性氟烷基碘烷中间体的机理。该中间体可以在 各种分子内或分子间反应，导致新的1，1-、1，2-和1，3-氟官能化产物， 高度对映体富集形式。努力的方向是对新反应的机理阐明， 通过使用实际的氟化物源来实际实现它们。