Metal-Catalyzed Methods for Organic Synthesis

项目概要/摘要： 以通用和可靠的方式系统地构建高度官能化分子的能力 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。我们计划的工作包括钯- 用于形成芳族和杂环碳-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个方面是 涉及改进的配体的设计和用于芳族碳-杂原子键形成的方法。 我们在这一领域的工作被整个学术界和工业界用于制备复杂分子 并已成为合成化学家的主要方法。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商购获得并广泛使用。的 发明新的、更通用的、更用户友好的技术不仅可以获得重要的信息， 化合物，而且还能够有效地和选择性地修饰它们的手段。这使得化学家 合理地制备新的衍生物，减少副作用，改善性能。我们还在努力 高区域选择性、非对映体选择性和对映体选择性合成脂肪族化合物的铜催化方法 胺、铜催化的碳-碳键的不对称形成方法和双 铜和钯催化工艺。这项工作的一部分旨在设计新的更多 经济、环保和普遍适用的碳-碳形成方法 通过使用烯烃作为亲核试剂键合。我们希望发展化学， 标准的，高活性的反应物与更温和和有用的反应物。我们还将实施机械化 研究，以帮助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。我们所针对的底物代表了 常见于药物、天然产物、农用化学品和感官产品中的结构成分 材料.这些新技术的可用性将使其他人能够制备各种高度- 功能化的和结构多样的化合物，其中许多以前是不可接近的， 这将在一系列对人类健康直接重要的领域产生巨大影响。

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.