Metal-Catalyzed Methods for Organic Synthesis

项目摘要/摘要： 以一般和可靠的方式系统地构建高官能化分子的能力 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，尤其是制药业。我们建议的工作包括钯- 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。我们提出的化学反应的一个方面 涉及改进的配体的设计和芳香族碳-杂原子键的形成方法。 我们在这方面的工作被学术界和工业界广泛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，现在可以商业化和广泛使用。这个 新的、更通用、更用户友好的技术的发明将不仅允许访问重要的 不仅是能够有效和选择性地对化合物进行修饰的手段。这使得化学家 合理合成新的衍生物，副作用小，性能好。我们也在努力 铜催化高区域、非对映和对映选择性合成脂肪族化合物的方法研究 胺，铜催化的不对称形成碳-碳键的方法和对偶 铜和钯催化的过程。这项工作的一部分旨在设计更多新的 形成碳-碳的经济、环境和普遍适用的方法 通过使用烯烃作为亲核原分子来键合。我们希望发展化学，使我们能够取代 标准的、高活性的反应物，具有更多的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实用性。我们的目标底物具有代表性 药品、天然产品、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使其他人能够准备各种高度- 官能化和结构多样化的化合物，其中许多以前是无法获得的， 这将在对人类健康直接重要的一系列领域产生重大影响。

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.