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.

项目摘要/摘要 碳-碳双键可以说是有机化学中最重要的官能团。 除了它在定义结构中的中心地位外，通过以下方式产生两个邻近的立体生成碳原子的能力 双键末端的两个新键的引入将其提升到了这种稀有的状态。伯爵- 较少的反应被引入来实现双环的区域、非对映和对映选择性官能化。 具有良好一般性的债券。然而，直到最近，有机化学家才将注意力转向对映体- 控制硫、氯、溴、碘等主族元素的引入。 与更常见的元素碳、氮和氧相互作用。虽然耐人寻味，但这些最近的 报告构成了已知催化剂和概念在解决方案中的临时应用，以创建新的、 裂解对映体选择性转化。我们的长期目标是构建机械/物理的有机 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。 这个建议的主要目的是：(1)应用路易斯酸的路易斯碱活化的概念 在这些实验室中开发，激活主要组中16和17组中的亲电物种，(2)学习 结构/反应性相关性和获得高催化活性的规则(转换频率和 (3)设计具有高立体选择性的手性路易斯碱 以及引入新的碳和杂原子取代的立体中心的高化学转化率， 和(4)开展详细的机理(动力学、光谱、结晶学、计算)研究 新发明的催化反应如下所述。 第一项主要工作将是扩大催化的、对映选择性的硫代官能化反应，以 许多底物类。链节烯烃的直接官能化和环官能化 亲氧基团(氧、氮、碳)是产生立体定义的链、杂环和 碳环。影响立体选择性硫代官能化反应的新型拓扑结构Lewis碱性催化剂 将在许多这样的转化中设计和评价E-和Z-烯烃。 第二个主要努力分为两个子目标，即开发催化的、对映体选择性的晕环。 官能化反应。用于这些极其重要的转变的催化剂的发展是 根据我们的论证，氯离子在构型上是稳定的，而溴和 而碘离子则不是。因此，这些转换的设计标准分为两个子目标：(1) 设计了一种催化剂，该催化剂提供了用于传送氯离子的对映面区分，以及(2) 为溴(碘)离子的传递提供对映面区分的催化剂的设计 并在捕获之前稳定中间体以防止外消旋。