Inverting Coupling Selectivity with Cooperative Metal-Ligand Constructs

通过协同金属配体构建体反转偶联选择性

• 批准号: 9808365
• 负责人: ALEXANDER T RADOSEVICH
• 金额: $ 23.96万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9808365
• 关键词: Address; Carbon; Catalysis; Chemicals; Chlorides; Complex; Coupling; Development; Drug Industry; Ethers; Event; Fluorides; Future; Goals; Health; Human; Knowledge; Ligands; Metals; Methodology; Methods; Modality; Outcome; Oxidation-Reduction; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phosphorus; Play; Positioning Attribute; Preparation; Reaction; Research; Research Project Grants; Role; Science; Services; Site; Technology; Thermodynamics; Transition Elements; Work; aryl halide; base; catalyst; chemical synthesis; design; drug candidate; drug discovery; drug synthesis; enthalpy; functional group; human disease; innovation; new technology; novel; small molecule; success; tool; trend

PROJECT SUMMARY/ABSTRACT Advances in catalytic science and technology enable the preparation of pharmaceutical agents used to treat human disease. Catalytic cross coupling reactions are among the most commonly employed reac- tions for the assembly of drugs and drug candidates in the pharmaceutical industry. Aryl ethers and fluo- rides are common intermediates in synthesis, but they are still considered to be challenging electrophiles for catalytic cross coupling. Catalytic methods that open this class of electrophile to cross coupling and allow their selective functionalization would significantly aid in the preparation of bioactive small mole- cules. This exploratory research project has the goal of developing a new technology for strong bond ac- tivation that will enable broad advances in catalytic cross coupling reactions of recalcitrant substrates. The first major milestone will be to establish the stoichiometric activation of aryl C–O and C–F bonds across metal-ligand cooperative constructs and to realize catalytic cross coupling of these electrophiles. The second major milestone will be to achieve selective activation of C–O and C–F substrates in the presence of other functionalizable moieties. The proposed research is expected to yield new practical catalytic methods for the construction of pharmacologically-relevant small molecules that meet the chal- lenges of selective synthesis. Also, the research will establish a new technology for catalytic coupling based on the conceptualization of metal-ligand constructs as cooperative functional engines for bond making and breaking. Taken together, these outcomes will transform the practice of catalytic strong bond activation by the introduction of a new and powerful modality in homogeneous catalysis.

项目概要/摘要 催化科学和技术的进步使得能够制备用于 催化交叉偶联反应是最常用的反应之一。 用于制药工业中的药物和候选药物的组装。 骑乘物是合成中常见的中间体，但它们仍然被认为是具有挑战性的亲电子试剂 用于催化交叉偶联，使此类亲电子试剂发生交叉偶联和 允许它们选择性功能化将显着有助于制备生物活性小分子 这个探索性研究项目的目标是开发一种用于强粘合作用的新技术。 这将使顽固底物的催化交叉偶联反应取得广泛进展。 第一个重要里程碑将是建立芳基 C-O 和 C-F 键的化学计量活化 跨越金属-配体协作结构并实现这些亲电子试剂的催化交叉偶联。 第二个重要里程碑是实现 C-O 和 C-F 底物的选择性激活 其他可功能化部分的存在预计将产生新的实用性。 用于构建满足化学性质的药理学相关小分子的催化方法 此外，该研究还将建立一种催化偶联新技术。 基于金属-配体结构作为键的协同功能引擎的概念 总而言之，这些结果将改变催化强键的实践。 通过在均相催化中引入新的、强大的方式来激活。