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个立体成分组成的非外消旋形式存在。这些特性突出了对新化学反应的迫切需求，这些反应允许化学家以高选择性有效地制备有机化合物。该研究计划的重点涉及开发新的立体选择性金属催化的碳-碳键形成过程，通过将1，1-双亲核试剂添加到许多类亲电试剂中。这些研究将导致战略性的替代C-C键断开，以对映体纯的形式提供重要的功能分子。本文所述的许多反应不具有现有的催化方案。(1)我们将开发实用和强大的铜催化的对映体和非对映体选择性烷基化羰基化合物及其衍生物与烷基含硼试剂;这些反应将导致一系列的非环状羟基和氨基硼酸酯的合成，不能很容易地通过其他方法访问。这些方法的价值通过安装高度通用的立体C-B键而增加。(2)我们将开发一般的对映收敛铜催化的过程中，一系列的烷基-，烯基-，芳基-，烯丙基-取代的1，1-杂环基亲核试剂的缺电子烯烃的加成。这种反应技术将导致更有效的方法来合成高烯丙醇和胺常见的化学结构中发现的生物活性分子。(3)反应的发展也将表明，1，1-二氯乙烷试剂提供了独特的方法，底物导向的立体选择性催化反应。该计划开发的新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路线。通过应用程序简明合成的抗肿瘤剂，我们将证明我们的方法的效用，除了确定其局限性。