Development of Strategies for the Functionalization of Amines

描述（由申请人提供）：大多数对人体健康至关重要的药物由含氮化合物组成。一种特别有吸引力的方法是通过C-H键功能化对廉价和容易获得的胺进行修饰。然而，有效完成这一任务的方法很少，而且严重缺乏范围。此外，目前已知的方法通常需要使用昂贵的过渡金属催化剂和/或氧化剂。本建议的重点是设计和开发有效和实用的胺功能化方法。主要目标是通过概念上新的和不发达的底物激活方法使胺的α-和ß-功能化。一个主要的焦点是氧化还原中性的方法来实现C-H键功能化，不需要昂贵的氧化剂或贵金属催化剂。我们提出的工作的中心主题是将氧化C-H键功能化与生产还原事件偶联，通过允许生成额外的C-C或C-X键来促进产物的形成。我们提出的反应通过在相对温和的条件下可以获得的亚胺、亚甲基和烯胺中间体进行。除了快速制备具有生物活性的化合物，如epiquinamide， harmicine和quinazolinone生物碱，我们的努力将集中在开发特别强大的反应，迅速产生新的多环胺。优先考虑的是生成当前药物发现筛选库中缺失的新结构框架。

DESCRIPTION (provided by applicant): The majority of pharmaceutical drugs that are essential for human health consist of nitrogen containing compounds. A particularly attractive approach to these targets is the modification of cheap and readily available amines by means of C-H bond functionalization. However, methods that accomplish this task efficiently are scarce and severely lacking in scope. Moreover, the currently known approaches typically require the use of expensive transition metal catalysts and/or oxidants. This proposal is focused on the design and development of efficient and practical methods for amine functionalization. The main goal is the α- and ß-functionalization of amines through conceptually new and underdeveloped methods of substrate activation. A major focus is on redox-neutral approaches to C-H bond functionalization that do not require expensive oxidants or precious metal catalysts. The central theme of our proposed work is to couple an oxidative C-H bond functionalization with a productive reduction event that contributes to the formation of products by allowing for the generation of additional C-C, or C-X bonds. Our proposed reactions proceed via iminium ion, azomethine ylide and enamine intermediates that can be accessed under relatively mild conditions. In addition to targeting the rapid preparation of biologically active compounds such as epiquinamide, harmicine and quinazolinone alkaloids, our efforts will center on the development of particularly powerful reactions that rapidly generate new polycylic amines. A priority is the generation of novel structural frameworks that are absent from current drug discovery screening libraries.