Metal-Catalyzed Methods for Organic Synthesis

金属催化有机合成方法

• 批准号: 9275662
• 负责人: STEPHEN L BUCHWALD
• 金额: $ 89.38万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9275662
• 关键词: Academia; Adverse effects; Agrochemicals; Amination; Amines; Area; Biological; Biomedical Research; Carbon; Chemistry; Complex; Copper; Coupling; Development; Drug Industry; Fluorine; Group Processes; Health; Human; Improve Access; Industry; Metals; Methods; Natural Products; Nitrogen; Organic Synthesis; Oxygen; Palladium; Pharmacologic Substance; Preparation; Process; Property; Vertebral column; Work; analog; drug discovery; invention; new technology; scale up; sensor

Project Summary/Abstract: The ability to prepare highly functionalized molecules in a general and predictable way is central to organic synthesis and the backbone of drug discovery, development and scale-up. The chemistry that we are proposing involves the development of carbon-heteroatom and carbon- carbon bond formations. Our prior work is widely used throughout academia and industry for the preparation of complex molecules and has become mainstay processes for synthetic chemists. The invention of new methods will not only allow access to important compounds but also the means to be able to efficiently and selectively modify them, to change their properties and or/eliminate side effects. Included in our proposed work are palladium-catalyzed cross coupling methods for the formation of heterocyclic carbon-nitrogen bonds, carbon-oxygen bonds and carbon-fluorine bonds; copper-catalyzed methods for the highly regio-, diastereo-, and enantioselective synthesis of aliphatic amines; and copper-catalyzed methods for the asymmetric formation of carbon-carbon bonds. Mechanistic studies will be conducted to understand the fundamental features of these transformations and will guide us to advance the efficiency and utility of this work. The substrates we are targeting are ubiquitous structural components in pharmaceuticals, natural products, agrochemicals and sensors. The application of these new technologies for the preparation of highly functionalized and diverse compounds, which have previously been inaccessible, will have a great impact in a range of areas that are directly important to human health.

项目摘要/摘要： 以通用且可预测的方式制备高功能化分子的能力是核心 有机合成以及药物发现、开发和放大的支柱。这 我们提议的化学涉及碳杂原子和碳杂原子的开发 碳键形成。我们之前的工作在学术界和工业界广泛使用 复杂分子的制备已成为合成化学家的主要工艺。 新方法的发明不仅可以获取重要的化合物，还可以 意味着能够有效地、有选择地修改它们，改变它们的属性和 或/消除副作用。我们提出的工作包括钯催化交叉偶联 杂环碳氮键、碳氧键的形成方法 碳-氟键；铜催化方法用于高度区域、非对映和 脂肪胺的对映选择性合成；和铜催化方法 碳-碳键的不对称形成。将进行机理研究 了解这些转变的基本特征并将指导我们推进 这项工作的效率和效用。我们针对的底物是普遍存在的结构 药品、天然产物、农用化学品和传感器中的成分。应用 这些用于制备高功能化和多样化化合物的新技术， 以前无法进入的领域将在一系列领域产生巨大影响 对人类健康直接重要。