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： 以一般且可预测的方式制备高度功能化的分子的能力是中心 有机合成和药物发现，开发和扩大规模的骨干。这 我们提出的化学涉及碳杂原子和碳的发展 碳键形成。我们先前的工作在整个学术界和行业中被广泛用于 复杂分子的制备，已成为合成化学家的主要过程。 新方法的发明不仅允许访问重要化合物，还可以 手段能够有效，有选择地修改它们，更改其属性和 或/消除副作用。我们建议的工作包括钯催化的交叉耦合 形成杂环碳氮键，碳氧键和形成的方法 碳氟键；高度区域，iatereo-和 脂肪族胺的对映选择性合成；和铜催化方法 碳碳键的不对称形成。机械研究将进行 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。我们靶向的底物是无处不在的结构 药品，天然产品，农业化学和传感器中的组件。应用程序 这些新技术用于制备高度功能化和多样化的化合物 以前无法访问的，将在一系列领域产生巨大影响 对人类健康直接重要。