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.

项目摘要/摘要 催化科学和技术的进步使制剂可以制备过去 治疗人类疾病。催化交叉耦合反应是最常用的recc- 制药行业中毒品和候选药物的组装。芳基醚和氟 游乐设施是综合中常见的中间体，但仍被认为是挑战的电力 用于催化交叉耦合。催化方法打开这类亲电的催化器，以交叉耦合和 允许其选择性功能化将显着有助于制备生物活性小摩尔 - Cules。该探索性研究项目的目的是开发一种新技术，以实现牢固的纽带 将恢复底物的催化交叉耦合反应的广泛进步。 第一个主要的里程碑是建立芳基C – O和CF键的化学计量激活 跨金属配体合作构建体，并实现这些电力物的催化交叉耦合。 第二个主要里程碑将是实现在C – O和CF底物中的选择性激活 存在其他功能性的部分。拟议的研究预计将产生新的实用性 用于构建与Chal-的相关小分子的催化方法 选择性合成的镜头。此外，该研究将建立一项新技术用于催化耦合 基于金属配体构建体的概念化，作为键合的合作功能引擎 制作和破坏。综上所述，这些结果将改变催化强键的实践 通过引入均质催化中的新型和强大的方式激活。