Asymmetric Catalysis in Main Group Chemistry

主族化学中的不对称催化

基本信息

批准号：
9208778
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
项目类别：
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

项目摘要

DESCRIPTION (provided by applicant): 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. Countless 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 enantiocontrolled introduction of elements in the main group such as sulfur, chlorine, bromine and iodine, in combination 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, catalytic 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 nucleophile (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 halofunctionalization 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.

描述（由申请人提供）：碳-碳双键可以说是所有有机化学中最重要的官能团。除了它在定义中的中心地位结构中，通过在双键末端引入两个新键来创建两个邻位立体碳原子的能力将其提升到了这种稀有状态。已经引入了无数反应来实现双键的区域、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主族元素（如硫、氯、溴和碘）与更常见的元素碳、氮和氧的对映控制引入。尽管很有趣，但这些最近的报告构成了已知催化剂和概念在创建新的催化对映选择性转化的解决方案中的临时应用。我们的长期目标是为发展普遍适用和高选择性的烯烃官能化反应构建机械/物理有机基础。该提案的主要目标是：(1) 应用这些实验室开发的路易斯酸的路易斯碱活化概念，活化主族中第 16 族和第 17 族中的亲电子物质，(2) 了解结构/反应性相关性和实现目标反应高催化活性（周转频率和周转数）的规则，（3）设计手性路易斯碱，该碱将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，以及(4)对下述新发明的催化反应进行详细的机理（动力学、光谱、晶体学、计算）研究。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底物类别。带有束缚亲核试剂（氧、氮、碳）的烯烃的直接官能化和环官能化是创建立体链、杂环和碳环的有效方法。将在许多此类转化中设计和评估可以影响E-和Z-烯烃的立体选择性磺基官能化的新型拓扑的路易斯碱性催化剂。第二个主要努力分为两个子目标，即开发催化、对映选择性卤代官能化反应。我们的证明指导了用于这些极其重要的转化的催化剂的开发，即氯离子是构型稳定的，而溴离子和碘离子则不稳定。因此，这些转化的设计标准分为两个子目标：（1）为氯鎓离子的传递提供对映体面差异的催化剂设计，以及（2）为氯鎓离子的传递提供对映体面差异的催化剂设计溴（碘）离子并在捕获之前稳定中间体以防止外消旋化。