Metal-Catalyzed Methods for Organic Synthesis

项目摘要： 实现高效和选择性转化以形成碳-碳的能力 和碳-杂原子键是我们母基金中描述的研究的主要目标 （GM122483）。我们寻求开发新的过渡金属催化方法， 使用方便，并对有机合成领域产生重大影响，特别是在 药物研究。我们目前的工作涉及钯催化的C-N交叉偶联， C-O和C-F键以及铜催化的区域选择性和对映选择性的方法 C-N和C-C键的构建。在新方法的开发中，我们尝试探索 不同的底物范围，以了解这些协议的适用性和通用性。对 平均而言，我们公布的方法每个都有>20个底物，我们详细介绍了at 至少两次独立实验以确保重现性，并通过以下方法纯化化合物： 快速柱色谱法。我们正在寻求更新和更换我们的自动化 由于我们现有设备的使用年限（6年和9年）以及 每天依靠该系统进行净化的研究人员人数（33名用户）， 化合物的分离。新的自动化系统将提高效率（速度提高2-3倍 比手动色谱法），减少溶剂浪费（环境友好）， 提高可靠性（目前的设备因维修而停机时间很长）。这将 极大地促进了我们在开发和优化新的C- C和C-X键的形成。

Project Summary: The ability to achieve efficient and selective transformations for the formation of carbon-carbon and carbon-heteroatom bonds is the primary goal of the research described in our parent grant (GM122483). We seek to develop new transition metal-catalyzed methods that are general, user-friendly, and have a significant impact on the field of organic synthesis, particularly in pharmaceutical research. Our current work involves palladium-catalyzed cross coupling for C–N, C–O and C–F bonds and copper-catalyzed processes for the regio- and enantioselective construction of C–N and C–C bonds. In the development of new methods, we try to explore diverse substrate scopes to understand the applicability and generality of these protocols. On average, our published methods each have >20 substrates, we detail the isolated yields of at least two independent experiments to ensure reproducibility and the compounds are purified by flash column chromatography. We are seeking to update and replace our automated chromatography system due to the age of our current equipment (6 and 9 years old) and the number of researchers (33 users) that rely on the system on a daily basis for the purification and isolation of compounds. A new automated system would increase efficiency (2-3 times faster than manual chromatography), decrease solvent waste (environmentally friendly), and have improved reliability (current equipment has had extensive downtime due to repairs). This would greatly facilitate our research efforts in the development and optimization of new methods of C– C and C–X bond formations.