Metal-Catalyzed Methods for Organic Synthesis

金属催化有机合成方法

• 批准号: 10406686
• 负责人: STEPHEN L BUCHWALD
• 金额: $ 114.2万
• 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 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10406686
• 关键词: Academia; Agrochemicals; Alkenes; Amines; Area; Benign; Biomedical Research; Carbon; Chemistry; Complex; Copper; Coupling; Development; Drug Industry; Fluorine; Group Processes; Health; Human; Improve Access; Industry; Lead; Ligands; Metals; Methods; Molecular; Natural Products; Nitrogen; Organic Chemistry; Organic Synthesis; Oxygen; Palladium; Pharmacologic Substance; Preparation; Process; Property; Sensory; Techniques; Work; analog; catalyst; design; drug development; drug discovery; improved; invention; new technology; scale up; side effect; user-friendly

Project Summary/Abstract: The ability to systematically construct highly functionalized molecules in a general and reliable manner is central to synthetic organic chemistry and key for drug discovery, development, and scale-up in both academia and, in particular, the pharmaceutical industry. Our proposed work includes palladium- catalyzed cross coupling methods for the formation of aromatic and heterocyclic carbon-nitrogen bonds, carbon-oxygen bonds and carbon-fluorine bonds. One aspect of the chemistry that we are proposing involves the design of improved ligands and methods for aromatic carbon-heteroatom bond formation. Our work in this area is used throughout academia and industry for the preparation of complex molecules and has become mainstay processes for synthetic chemists. As part of this, we have developed numerous new ligands and catalysts that are now commercially available and widely employed. The invention of new, more general, and more user-friendly techniques will not only allow access to important compounds but also the means to be able to efficiently and selectively modify them. This allows chemists to rationally make new derivatives, with decreased side effects and better properties. We are also working on copper-catalyzed methods for the highly regio-, diastereo-, and enantioselective synthesis of aliphatic amines, copper-catalyzed methods for the asymmetric formation of carbon-carbon bonds and dual copper- and palladium-catalyzed processes. A portion of this work aims to design new more economically, environmentally, and generally applicable methods for the formation of carbon-carbon bonds by using alkenes as pronucleophiles. We wish to develop chemistry that will allow us to replace standard, highly reactive reactants with more benign and useful ones. We will also carry out mechanistic studies to help understand the fundamental features of these transformations and to help guide us in advancing the efficiency and utility of this work. The substrates we are targeting are representative of common structural components found in pharmaceuticals, natural products, agrochemicals, and sensory materials. The availability of these new technologies will allow others to prepare a variety of highly- functionalized and structurally diverse compounds, many of which have previously been inaccessible, which will have a great impact in a range of areas that are directly important to human health.

项目摘要/摘要： 以通用且可靠的方式系统地构建高度功能化分子的能力 是合成有机化学的核心，也是药物发现、开发和放大的关键 学术界，特别是制药业。我们提议的工作包括钯- 用于形成芳香族和杂环碳-氮键的催化交叉偶联方法， 碳-氧键和碳-氟键。我们提出的化学的一方面 涉及改进的配体设计和芳香碳-杂原子键形成方法。 我们在这一领域的工作被整个学术界和工业界用于复杂分子的制备 并已成为合成化学家的主要工艺。作为其中的一部分，我们开发了 许多新的配体和催化剂现已商业化并广泛使用。这 新的、更通用的、更用户友好的技术的发明不仅将允许访问重要的信息 化合物，而且还提供了能够有效、选择性地修饰它们的方法。这使得化学家 合理制备新的衍生物，副作用减少，性能更好。我们也在工作 铜催化脂肪族化合物高度区域选择性、非对映选择性和对映选择性合成方法 胺、铜催化不对称形成碳-碳键和双键的方法 铜和钯催化的过程。这项工作的一部分旨在设计更多新的 经济、环保且普遍适用的碳-碳形成方法 通过使用烯烃作为亲核试剂进行键合。我们希望开发出化学方法来取代 标准的高反应性反应物与更良性和有用的反应物。我们还将进行机械化 研究有助于理解这些转变的基本特征并帮助指导我们 提高这项工作的效率和效用。我们针对的基材具有代表性 药物、天然产物、农用化学品和感官中常见的结构成分 材料。这些新技术的出现将允许其他人准备各种高度 功能化且结构多样的化合物，其中许多以前无法获得， 这将对一系列与人类健康直接重要的领域产生巨大影响。