Asymmetric Catalysis in Main Group Chemistry

描述(申请人提供)：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 在结构上，通过在双键末端引入两个新的键来创建两个邻近的立体致密碳原子的能力将其提升到这种稀有状态。为了实现双键的区域功能化、非对映功能化和对映选择性功能化，引入了无数的反应，具有很好的通用性。然而，直到最近，有机化学家才将他们的注意力转向对映体控制地引入主要族元素，如硫、氯、溴和碘，以及更常见的元素碳、氮和氧。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的临时应用，以解决创建新的催化对映体选择性转化的问题。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建立机制/物理有机基础。这项建议的主要目标是：(1)应用这些实验室开发的Lewis碱激活Lewis酸的概念，激活主基团中第16和17族中的亲电物种，(2)了解结构/反应活性相关性和获得目标反应的高催化活性(周转频率和周转次数)的规则，(3)设计将为引入新的碳和杂原子取代立体中心提供高立体选择性和高化学转化率的手性Lewis碱，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、结晶学、计算)研究。第一个主要的努力将是将催化的、对映选择性的硫代官能化反应扩展到许多底物类别。直接官能化和环官能化是合成立体定义的链、杂环和碳环的有效方法。可以影响E-和Z-烯烃的立体选择性硫代官能化的新型拓扑结构的Lewis碱性催化剂将在许多这些转化中被设计和评估。第二项主要工作分为两个子目标，即开发催化的、对映选择性的卤代功能化反应。这些极其重要的转变的催化剂的开发是由我们的论证指导的，即氯离子是构型稳定的，而溴和碘离子不是。因此，这些转化的设计标准分成两个子目标：(1)设计催化剂，为传递氯离子提供对映体表面分化；(2)设计催化剂，为传递溴(碘)离子提供对映体表面分化，并在捕获之前稳定中间体以防止外消旋。

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.