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.

项目概要/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，还能够通过以下方式创建两个邻位立体碳原子： 在双键末端引入两个新键使其达到了这种稀有的状态。数数- 引入较少的反应来影响双分子的区域、非对映和对映选择性官能化 具有良好通用性的债券。然而，直到最近，有机化学家才将注意力转向对映体 控制引入主族元素，如硫、氯、溴和碘，结合 与更常见的元素碳、氮和氧的化合。虽然很有趣，但最近的这些 报告构成了已知催化剂和概念的临时应用，以解决创造新的催化剂的问题。 裂解性对映选择性转化。我们的长远目标是构建机械/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。 该提案的主要目标是：（1）应用路易斯酸的路易斯碱活化概念 在这些实验室开发的，激活主组中第 16 组和第 17 组的亲电物种，(2) 学习 结构/反应性相关性以及实现高催化活性的规则（周转频率和 转换数）的目标反应，（3）设计手性路易斯碱，以赋予高立体选择性 和高化学转化率以引入新的碳和杂原子取代的立体中心， (4) 进行详细的机理（动力学、光谱、晶体学、计算）研究 新发明的催化反应如下所述。 第一个主要努力是将催化、对映选择性磺基官能化反应扩展到 许多基材类别。带有束缚核的烯烃的直接官能化和环官能化 亲电体（氧、氮、碳）是创建立体链、杂环和 碳环。新型拓扑路易斯碱性催化剂可实现立体选择性磺基官能化 E-和Z-烯烃的设计和评估将在许多此类转化中进行。 第二个主要努力分为两个子目标，是开发催化的、对映选择性的卤代化合物。 功能化反应。这些极其重要的转变的催化剂的开发是 以我们的证明为指导，氯离子是构型稳定的，而溴和 碘离子则不然。因此，这些转换的设计标准分为两个子目标：（1） 设计为传递氯离子提供对映体面差异的催化剂，以及（2） 设计提供对映体面差异以传递溴（碘）离子的催化剂 并在捕获前稳定中间体以防止外消旋化。