N-保護-3-硝基吲哚和2-氨基苯扎丙酮的不對稱有機催化形式 [4+2] 環加成反應

Abstract

近年來，發現一些具有生物活性的天然物，都有著四氫-5H-吲哚并[2,3-b]喹啉的核心骨架。過去的文獻中，對於此類架構合成必須透過金屬催化劑控制立體選擇性，直接使用3-硝基吲哚搭配不對稱有機催化方法尚未被發表。本研究首次展示透過不對稱有機催化形式[4+2]環加成反應，構建四氫-5H-吲哚并[2,3-b]喹啉衍生物。使用雙功能金雞納生物鹼方醯胺催化劑，對3-硝基吲哚和甲基-2-(甲苯磺酰氨基)苯基α,β-不飽和酮，在溫和的反應條件下，進行鏡像選擇性有機催化反應，合成一系列含有三個連續立體中心的四氫-5H-吲哚并[2,3-b]喹啉衍生物，得到良好的產率（高達60%）和高度立體選擇性（高達15:1 dr和98% ee）。

In recent years, some biologically active natural products have been found to have the core skeleton of tetrahydro-5H-indolo[2,3-b]quinoline. In the past literature, the stereoselectivity must be controlled by metal catalysts for this type of architecture synthesis, and the direct use of 3-nitroindole with asymmetric organocatalysis methods has not been published. This study features the first asymmetric organocatalytic formal for constructed tetrahydro-5H-indolo[2,3-b]quinolines derivatives.An organocatalytic enantioselective synthesis of tetrahydro-5H-indolo[2,3-b]quinolines derivatives was demonstrated using 3-nitroindoles and methyl 2-(tosylamino)phenyl α,β-unsaturated ketones in the presence of the bifunctional cinchona alkaloids squaramide catalyst. A series of tetrahydro-5H-indolo[2,3-b]quinolines derivatives containing three continuous stereogenic centers were obtained in good yields (up to 60%) and with high stereoselectivities (up to 15:1 dr and up to 98% ee).