Metal-Catalyzed Methods for Organic Synthesis

项目概要/摘要： 以通用和可预测的方式制备高度官能化分子的能力是核心 到有机合成和药物发现、开发和放大的支柱。的 我们提出的化学涉及碳-杂原子和碳- 碳键的形成我们先前的工作被广泛用于整个学术界和工业界， 复杂分子的制备，并已成为合成化学家的支柱工艺。 新方法的发明不仅可以获得重要的化合物， 意味着能够有效地和选择性地修饰它们，改变它们的性质， 或/消除副作用。我们的工作包括钯催化的交叉偶联 形成杂环碳-氮键、碳-氧键和 碳-氟键;铜催化法制备高度区域-、非对映-和 脂肪胺的对映选择性合成;以及铜催化的 碳-碳键的不对称形成。将进行机制研究， 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。我们所针对的底物是普遍存在的结构性的 医药、天然产品、农用化学品和传感器中的零部件。应用 在这些用于制备高度官能化和多样化的化合物的新技术中， 以前无法进入的，将在一系列领域产生巨大影响， 对人类健康有直接的重要性。

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.