Frustrated Lewis Pair catalyzed cycloisomerization initiated by hydride abstraction

受阻路易斯对催化氢化物夺取引发的环异构化

• 批准号: 398114720
• 负责人: Professor Dr. Jan Paradies
• 金额: --
• 依托单位: Mulliken Center for Theoretical Chemistry
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/398114720?language=en
• 关键词: Frustrated; Lewis; Pair; catalyzed; cycloisomerization

Cycloisomerizations, cycloadditions and electrocyclizations are powerful tools for the synthesis of complex molecular frameworks bearing quaternary stereogenic centers. In particular, iminium ions are recognized as reactive intermediates to induce such reactions. While acyclic tertiary iminium ions are readily accessible e.g. though condensation, substantial synthetic effort is required for the synthesis of the corresponding cyclic derivatives. However, the formation of iminium ions has been observed in frustrated Lewis pair-catalyzed reactions, which breaks new ground for the efficient access to these reactive intermediates.This research project takes advantage of this so far unexploited synthetic potential for the catalytic C–C bond forming reaction in the synthesis of quinoline derivatives bearing quaternary stereocenters. This important molecule class is obtained by hydride abstraction-initiated electrocyclization of catalytically formed iminium ions. The flexible substitution pattern opens up for the efficient access to polycyclic alkaloid derivatives with quaternary stereocenters. Furthermore, not only tetrahydroquinolines but also dihydroquinolines are accessible by this new catalytic approach. Through the choice of the catalyst the reaction can be directed to the redoxneutral cycloisomerization or to the so far unprecedented dehydrogenative cycloisomerization accessing two pharmacologically important product classes from the same substrate.

环异构化、环加成和电环化反应是合成具有四元立体中心的复杂分子骨架的有力工具。特别地，亚胺离子被认为是诱导这种反应的反应性中间体。虽然无环叔亚胺鎓离子是容易获得的，例如通过缩合，但合成相应的环状衍生物需要大量的合成努力。然而，在受阻的刘易斯对催化反应中观察到亚胺离子的形成，这为有效获得这些活性中间体开辟了新的天地。这类重要的分子是通过氢化物提取引发的催化形成的亚胺离子的电环化而获得的。灵活的取代模式开辟了有效地获得多环生物碱衍生物与季立体中心。此外，不仅四氢喹啉，而且二氢喹啉可通过这种新的催化方法获得。通过催化剂的选择，反应可以被导向氧化还原中性环化异构化或迄今为止前所未有的从同一底物获得两种重要产物类别的双价环化异构化。