酰胺的“一瓶”催化不对称还原型Bischler-Napieralski反应：生物活性1-取代四氢异喹啉的对映选择性合成

doi:10.6023/A25120419

摘要/Abstract

本文利用先官能化再还原的酰胺不对称还原转化新策略实现了酰胺的“一瓶”催化不对称还原型Bischler-Napieralski反应。该方法涉及串联进行的三氟甲磺酸酐/2-氟-吡啶（Tf₂O/2-F-Pyr.）促进的Bischler-Napieralski脱水环化以及水相Noyori型催化不对称转移氢化（CATH）反应。通过此一瓶法,以高收率和优异的对映选择性合成了一系列四氢异喹啉衍生物。该方法适用于酰基部分带有富电子或缺电子基团的N-芳乙基芳香酰胺,以及N-芳乙基脂肪酰胺。并通过这一方法实现了四种生物碱,(S)-猪毛菜定碱、(S)-劳丹宁、(S)-木防己碱、(S)-N-去甲劳丹宁,以及药物分子ACT-335827的高效、催化对映选择性合成。此外,还实现了生物碱(S)-Cryptostyline III及药物分子almorexant的形式合成。

关键词: 酰胺, 酰胺活化, 四氢异喹啉, Bischler-Napieralski型环化, 催化不对称转移氢化, 生物碱

Herein, we report the one-pot, catalytic asymmetric reductive Bischler-Napieralski-type reaction of amides as the first demonstration of a new strategy for the asymmetric reductive transformation of amides, which allowed for the one-pot, enantioselective entrance to tetrahydroisoquinoline (THIQ). The method features a tandem sequence involving the Tf₂O/2-F-Pyr.-promoted Bischler-Napieralski dehydracyclization and an aqueous Noyori-type catalytic asymmetric transfer hydrogenation (CATH). By this one-pot method, a variety of THIQ derivatives were synthesized in high yields and in excellent enantioselectivities. This protocol accommodates N-arylethyl aromatic amides bearing either electron-rich or electron-deficient group on the acyl moiety, and N-arylethyl aliphatic amides. The synthetic utility of this methodology was demonstrated via the efficient, catalytic enantioselective synthesis of four alkaloids: (S)-salsolidine, (S)-laudanosine, (S)-xylopinine, and (S)-N-norlaudanidine, and medicinal agent ACT-335827. Additionally, formal synthesis of alkaloid (S)-cryptostyline III and medicinal agents such as almorexant was achieved.

Key words: amide, amide activation, tetrahydroisoquinoline, Bischler-Napieralski-type cyclization, catalytic asymmetric transfer hydrogenation, alkaloid

引用此文

卢广生, 韩增, 叶剑良, 黄培强. 酰胺的“一瓶”催化不对称还原型Bischler-Napieralski反应：生物活性1-取代四氢异喹啉的对映选择性合成[J]. 化学学报, doi: 10.6023/A25120419.

Lu Guang-Sheng, Han Zeng, Ye Jian-Liang, Huang Pei-Qiang. One-pot, Catalytic Asymmetric Reductive Bischler-Napieralski-Type Reaction of Amides: An Enantioselective Entrance to Biologically Active 1-Substituted Tetrahydroisoquinolines[J]. Acta Chimica Sinica, doi: 10.6023/A25120419.

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