Catalytic, Enantioselective Dihalogenation of Alkenes

在这项由化学系化学催化计划资助的项目中，伊利诺伊大学厄巴纳-香槟分校的斯科特·E·丹麦教授正在进行研究，以开发一种新的烯烃催化、对映选择性二氯化反应范式。添加到不饱和化合物是最古老和最可靠的立体专一性转化。然而，事实证明，控制产品的绝对配置的问题具有挑战性。越来越多的在立体形成中心含有卤素原子的复杂天然产品突显了合成方法学的这一严重缺陷。这一建议解决了对映选择性二卤化反应过程设计中固有的选择性挑战，并为烯烃二卤化反应制定了基于机理的解决方案，包括那些绕过经典卤素(或烯烃-二卤代pi络合物)中间体的解决方案。丹麦教授设计了一种新的方法，通过使用一种基于硒的特殊设计的催化剂来逆转双键上经典的“反”加成。由此产生的双键的“SYN加成”使得对映体选择性变体的合理发展成为可能。这对社会有几个好处：第一，提供高技能的劳动力，以帮助我们以化学为基础的行业的经济健康发展。第二，化学催化的重要性怎么估计都不为过，因为它占美国GDP的20%以上。鉴于化工企业的许多领域都强调单一对映体物质，目前对提供这种材料的新的通用和选择性工艺非常感兴趣。这一建议的主要目标是为利用两种不同的催化模式开发普遍适用和高选择性的烯烃二卤化反应建立机制/物理有机基础。这两种模式构成了本项目的两个具体目标，即：(1)氧化还原活性主基催化和(2)不对称相转移催化。在每个特定的目标中，我们是：(1)了解目标反应的结构/反应性相关性和获得高催化活性(周转频率和周转次数)的规则；(2)对新发明的催化反应进行详细的机理研究；(3)设计具有高立体选择性和高化学转化率的手性催化剂，以引入新的邻位立体中心；(4)展示代表有用和常见结构基元的各种底物类别的一般性。该奖项支持为丹麦小组的年轻科学家提供良好的培训环境。

In this project funded by the Chemical Catalysis Program of the Chemistry Division, Professor Scott E. Denmark at the University of Illinois at Urbana-Champaign is conducting research to develop a new paradigm for the catalytic, enantioselective dichlorination of alkenes. Addition to unsaturated compounds is among the oldest and most reliable of stereospecific transformations. However, the problem of controlling the absolute configuration of the products has proved challenging. The growing number of complex natural products bearing halogen atoms at stereogenic centers has underscored this critical deficiency in synthetic methodology. This proposal addresses the selectivity challenges inherent in the design of enantioselective dihalogenation processes, and formulates mechanism-based solutions to alkene dihalogenations, including those that circumvent the classical haliranium (or alkene-dihalogen pi-complex) intermediates. Professor Denmark has devised a new approach that inverts the classical "anti" addition to the double bonds by the use of a specially designed catalyst based on selenium. The resulting "syn addition" to double bonds enables the rational development of an enantioselective variant. There are several benefits to society: first in providing a highly skilled workforce to aid in the economic health of our chemistry-based industries. Second, the significance of chemical catalysis cannot be overestimated as it accounts for over 20% of the USA GDP. Given the emphasis on single enantiomer substances in many reaches of the chemical enterprise, new general and selective processes that provide such materials are of great current interest. The primary objective of this proposal is to construct the mechanistic/physical organic foundation for the development of generally applicable and highly selective alkene dihalogenations reactions using two different modes of catalysis. These two modes constitute the two Specific Aims of this project, namely: (1) redox active main group catalysis and (2) asymmetric phase transfer catalysis. Within each Specific Aim, we are: (1) learning the structure/reactivity correlations and the rules for achieving high catalytic activity (turnover frequencies and turnover numbers) for the target reactions, (2) carrying out detailed mechanistic investigations of the newly invented catalytic reactions, and (3) designing chiral catalysts that impart high stereoselectivity and high chemical conversion for the introduction of new vicinal stereocenters and (4) demonstrating generality in a variety of substrate classes that represent useful and commonly encountered structural motifs. This award supports an excellent training environment for young scientists in the Denmark group.