Asymmetric Catalysis in Main Group Chemistry

主族化学中的不对称催化

• 批准号: 8635171
• 负责人: Scott Eric Denmark
• 金额: $ 28.89万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-22 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635171
• 关键词: Acids; Alkenes; Attention; Bromine; Carbon; Catalysis; Charge; Chemicals; Chemistry; Chlorine; Complex; Development; Dissociation; Elements; Face; Foundations; Frequencies; Goals; Indium; Investigation; Iodine; Ions; Kinetics; Laboratories; Learning; Methods; Nitrogen; Organic Chemistry; Organic Synthesis; Oxygen; Positioning Attribute; Process; Reaction; Reporting; Research Proposals; Scheme; Solutions; Structure; Sulfur; base; catalyst; chemical reaction; design; functional group; novel; pi bond; programs; public health relevance; racemization

PROJECT SUMMARY/ABSTRACT The carbon-carbon double bond is arguably the most important functional group in all of organic chemistry. Aside from its central position in defining structure, the ability to create two vicinal stereogenic carbon atoms by the introduction of two new bonds at the termini of a double bond has elevated it to this rarefied status. Count- less reactions have been introduced to effect regio, diastereo and enantioselective functionalization of double bonds with good generality. However, only recently have organic chemists turned their attention to the enantio- controlled introduction of elements in the main group such as sulfur, chlorine, bromine and iodine, in combina- tion with the much more common elements carbon, nitrogen and oxygen. Although intriguing, these recent reports constitute an ad hoc application of known catalysts and concepts to the solution of creating new, cata- lytic enantioselective transformations. Our long-term goal is to construct the mechanistic/physical organic foundation for the development of generally applicable and highly selective alkene functionalization reactions. The primary objectives of this proposal are to: (1) apply the concept of Lewis base activation of Lewis acids developed in these laboratories, activate electrophilic species in Groups 16 and 17 in the Main Group, (2) learn the structure/reactivity correlations and the rules for achieving high catalytic activity (turnover frequencies and turnover numbers) for the target reactions, (3) design chiral Lewis bases that will impart high stereoselectivity and high chemical conversion for the introduction of new carbon and heteroatom substituted stereocenters, and (4) carry out detailed mechanistic (kinetic, spectroscopic, crystallographic, computational) investigations of the newly invented catalytic reactions described below. The first major effort will be the expansion of catalytic, enantioselective sulfenofunctionalization reactions to many substrate classes. Direct functionalization and cyclofunctionalization of alkenes bearing a tethered nu- cleophile (oxygen, nitrogen, carbon) is a powerful method for creating stereodefined chains, heterocycles, and carbocycles. Lewis basic catalysts of novel topology that can effect the stereoselective sulfenofunctionalization of E- and Z-alkenes will be designed and evaluated in many of these transformations. The second major effort, divided into two sub goals, is the development of catalytic, enantioselective halo- functionalization reactions. The development of catalysts for these extremely important transformations is guided by our demonstration that chloriranium ions are configurationally stable whereas bromiranium and iodiranium ions are not. Thus, the design criteria for these transformations diverge into two sub goals: (1) the design of catalysts that provide enantiotopic face differentiation for the delivery of a chlorenium ion, and (2) the design of catalysts that provide enantiotopic face differentiation for the delivery of a bromenium (iodenium) ion AND stabilize the intermediate against racemization prior to capture.

项目总结/摘要 碳-碳双键可以说是所有有机化学中最重要的官能团。 除了其在定义结构中的中心位置之外，通过以下方式产生两个邻位立体碳原子的能力也是重要的： 在双键的末端引入两个新的键使其提升到这种稀薄的状态。数数- 已经引入了较少的反应来实现双的区域、非对映和对映选择性官能化， 具有良好的通用性。然而，直到最近，有机化学家才将注意力转向对映体， 控制引入主族元素，如硫、氯、溴和碘， 与更常见的元素碳，氮和氧的反应。虽然有趣，但这些最近 这些报告构成了已知催化剂和概念的特别应用，以解决创建新的，cata， 裂解对映选择性转化。我们的长期目标是建立机械/物理有机 为开发普遍适用和高选择性的烯烃官能化反应奠定了基础。 该建议的主要目的是：（1）应用刘易斯酸的刘易斯碱活化的概念 在这些实验室开发，激活亲电物种在第16和17组的主要群体，（2）学习 结构/反应性相关性和实现高催化活性的规则（转换频率和 转换数）的目标反应，（3）设计手性刘易斯碱，将赋予高立体选择性 以及用于引入新的碳和杂原子取代的立构中心的高化学转化率， 和（4）进行详细的机制（动力学，光谱学，晶体学，计算）调查， 新发明的催化反应如下所述。 第一个主要的努力将是扩大催化，对映选择性的磺基官能化反应， 许多基板类。含链核烯烃的直接官能化和环官能化 亲电体（氧、氮、碳）是用于产生立体定向的链、杂环和 碳环可实现立体选择性磺酰基官能化的新型拓扑结构的刘易斯碱性催化剂 的E-和Z-烯烃将设计和评估在许多这些转换。 第二个主要的努力，分为两个子目标，是催化的，对映选择性的卤代- 功能化反应为这些极其重要的转化开发催化剂是 在我们证明氯铱离子构型稳定，而溴铱离子和 碘离子则不是。因此，这些转换的设计标准分为两个子目标： 设计催化剂，其提供用于递送铼离子的对映异构体表面差异，和（2） 提供用于输送溴（碘）离子的对映异构面差异的催化剂的设计 并在捕获前稳定中间体以防止外消旋化。