Development of New Stereoselective Metal-Catalyzed Organic Reactions

新型立体选择性金属催化有机反应的发展

• 批准号: 9266600
• 负责人: Simon John Meek
• 金额: $ 9.89万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9266600
• 关键词: Address; Alcohols; Alkenes; Alkylation; Amines; Biological; Boron; Carbon; Characteristics; Chemical Structure; Chemicals; Complex; Coupling; Development; Electrons; Elements; Goals; Healthcare; Human; Lead; Metals; Methods; Molecular; Molecular Structure; Outcome; Pharmacologic Substance; Preparation; Process; Protocols documentation; Reaction; Reagent; Research; Route; Technology; Therapeutic Agents; Work; base; butyrolactone; carbene; catalyst; chemical reaction; chiral molecule; diene; functional group; improved; next generation; pi bond; programs; public health relevance; scaffold; small molecule

 DESCRIPTION (provided by applicant): Our ability to synthesize carbon-carbon bonds is integral to accessing the important biological activity of myriad organic molecules. Many valuable therapeutic agents exist in non-racemic form comprised of multiple stereogenic elements. Such characteristics highlight the critical need for new chemical reactions that allow chemists to efficiently prepare organic compounds with high levels of selectivity. The focus of this research program involves the development of new stereoselective metal-catalyzed processes for carbon-carbon bond formation via the addition of 1,1-bimetallic nucleophiles to a number of classes of electrophiles. These studies will lead to strategically alternative C-C bond disconnections that deliver important functional molecules in enantiomerically pure form. Many of the reactions described herein do not have existing catalytic protocols. (1) We will develop practical and robust Cu-catalyzed enantio-and diastereoselective alkylations of carbonyls and their derivatives with alkyl boron-containing reagents; these reactions will lead to the synthesis of a range of acyclic hydroxy- and amino-boronates that cannot be easily accessed by others methods. The value of these methods is increased by the installation of a highly versatile stereogenic C-B bond. (2) We will develop general enantioconvergent Cu-catalyzed processes for the addition of a range of alkyl-, alkenyl-, aryl-, allyl- substituted 1,1-heterobimetallic nucleophiles to electron-deficient alkenes. This reaction technology will lead to more efficient ways to synthesize homoallyl alcohols and amines common chemical structures found in bioactive molecules. (3) Reaction development will also demonstrate that 1,1-bimetallic reagents offer unique approaches to substrate-directed stereoselective catalytic reactions. The new catalysts and catalytic methods developed in this program offer unique and selective routes to the enantioselective synthesis of adaptable molecules. Through applications to concise synthesis of pharmacologically active agents, we will demonstrate the utility of our methods, in addition to identifying their limitations.

 描述（由申请人提供）：我们合成碳-碳键的能力对于获得无数有机分子的重要生物活性是不可或缺的，许多有价值的治疗剂以由多种立体元素组成的非外消旋形式存在。新的化学反应使化学家能够有效地制备具有高选择性的有机化合物，该研究计划的重点是开发通过添加碳-碳键形成的新立体选择性金属催化工艺。 1,1-双金属亲核试剂与多种亲电子试剂的结合将导致策略性的 C-C 键断裂，从而以对映体纯的形式提供重要的功能分子 (1)。我们将开发实用且稳健的铜催化的羰基及其衍生物与含烷基硼的对映和非对映选择性烷基化反应试剂；这些反应将导致一系列无法​​通过其他方法轻松获得的无环羟基硼酸酯和氨基硼酸酯的合成，这些方法的价值通过安装高度通用的立体 C-B 键而增加。我们将开发通用的对映异构铜催化工艺，用于加成一系列烷基、烯基、芳基、烯丙基取代的 1,1- 杂双金属该反应技术将带来更多合成生物活性分子中常见化学结构的醇和胺的方法。 (3) 反应的发展还将证明 1,1-双金属试剂提供了独特的有效底物方法。该项目开发的新型催化剂和催化方法为适应性分子的对映选择性合成提供了独特的选择性途径。药理活性剂的简明合成，除了确定其局限性外，我们还将展示我们的方法的实用性。