Enantioselective Reactions with Amide Electrophiles Utilizing Transition-Metal Catalysis

项目总结/摘要 有机合成在小分子药物的开发中起着至关重要的作用。新 允许引入限定的立体中心和难以接近的基序的方法， 例如四元立构中心。此外，人们越来越关注 使用非传统的合成积木来产生这种复杂性，因为使用不常见的 起始材料提供了新的策略和逆合成断开， 有用的. 拟议的研究涉及在过渡金属催化的反应中使用酰胺， 产生带有四元立构中心的对映体富集产物。虽然酰胺具有 在历史上，它们被避免作为合成结构单元，最近被用于过渡 通过C-N键活化进行的金属催化反应。然而，酰胺交叉偶联 制备季立体中心的方法是罕见的，并且没有催化的对映选择性实例， 被举报。拟议研究的成功将推动已知酰胺交叉的限制- 偶联方法，提供访问定义的四元立体中心的方法，并提供新的 合成化学家在药物和复杂分子的构建中使用的策略。

Project Summary/Abstract Organic synthesis plays a crucial role in the development of small molecule therapeutics. New methodologies that allow for the introduction of defined stereocenters and difficult-to-access motifs, such as quarternary stereocenters, are particularly desirable. Moreover, there is growing interest in the use of unconventional synthetic building blocks to generate such complexity, as the use of uncommon starting materials provides new strategies and retrosynthetic disconnections that may prove broadly useful. The proposed research involves the use of amides in transition metal-catalyzed reactions to generate enantioenriched products bearing quaternary stereocenters. Although amides have historically been avoided as synthetic building blocks, they have recently been employed in transition metal-catalyzed reactions that proceed via C–N bond activation. However, amide cross-coupling methods that make quaternary stereocenters are rare and no catalytic enantioselective examples have been reported. The success of the proposed studies would push the limits of known amide cross- coupling methodology, provide methods to access defined quaternary stereocenters, and offer new strategies for synthetic chemists to utilize in the construction of drugs and complex molecules.