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： 以一般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，也是两者中的药物发现，开发和扩大的关键 学术界，尤其是制药行业。我们提出的工作包括钯 - 催化的交叉耦合方法，用于形成芳族和杂环碳氮键， 碳氧键和碳氟键。我们提出的化学反应的一个方面 涉及改进的配体的设计和芳族碳杂质键形成的方法。 我们在该领域的工作在整个学术界和行业中都用于准备复杂分子 并已成为合成化学家的主要过程。作为其中的一部分，我们已经发展了 现在可商购且广泛使用的许多新配体和催化剂。这 发明新的，更一般和更易于用户友好的技术不仅可以访问重要 化合物，也是能够有效和有选择地修改它们的手段。这允许化学家 合理地制造新的衍生物，副作用降低和更好的特性。我们也在工作 关于高度区域，映射和对映选择性合成的铜催化方法 胺，铜催化的方法，用于碳 - 碳键和双重形成 铜和钯催化的过程。这项工作的一部分旨在设计更多 在经济，环境和通常适用的方法中，用于形成碳碳 通过将烷烃作为核寄移量来键。我们希望开发化学反应，使我们能够取代 标准，高反应反应物具有更良性和有用的反应物。我们还将执行机械 研究有助于了解这些转变的基本特征，并帮助我们指导我们 提高这项工作的效率和实用性。我们针对的基板代表 在药品，天然产物，农业化学和感觉中发现的常见结构成分 材料。这些新技术的可用性将使其他人能够准备各种高度的 功能化和结构上多样的化合物，其中许多以前是无法访问的， 这将在对人类健康直接重要的一系列领域产生巨大影响。