手性菲咯啉叔胺衍生的N-氧化物的合成及其在吲哚的不对称烷基化反应中的应用  

Synthesis of Chiral Phenanthroline-tertiary Amine Derived N-oxides and Their Application in Asymmetric Alkylation Reaction of Indole

作　　者：赵婉婷 胡盼 徐客兰 余章彪[1] 刘雄利[1] 邓国栋[1] ZHAO Wanting;HU Pan;XU Kelan;YU Zhangbiao;LIU Xiongli;DENG Guodong(National&Local Joint Engineering Research Center for The Exploition of Homology Resources of Medicine and Food,Guizhou University,Guiyang 550025,China)

机构地区：[1]贵州大学西南药食两用资源开发利用技术国家地方联合工程研究中心,贵州贵阳550025

出　　处：《合成化学》2024年第11期1000-1006,共7页Chinese Journal of Synthetic Chemistry

基　　金：国家地区基金资助项目(22361009)。

摘　　要：手性菲咯啉配体的多样性合成仍然是不对称催化领域重要的课题。本文以经济易得的各种取代的光学纯脯氨酰胺或羟脯氨酰胺(1)为起始原料,与菲咯啉-2-甲醛(2)发生缩合环化反应,合成了中间体3。中间体3继续在氧化剂间氯过氧苯甲酸(m-CPBA)的作用下发生叔胺氮原子上的氧化反应,合成了9个未见文献报道的手性菲咯啉叔胺衍生的N-氧化物4a~4i,总产率32%~35%,dr值为8/1~>20/1。化合物4结构经^(1)H NMR,^(13)C NMR和HR-MS(ESI-TOF)表征。此外,化合物4a~4i可用作配体参与金属催化吲哚(5)与β,γ-不饱和α-酮酯(6)的不对称Friedel-Crafts烷基化反应。其中,配体4i能够提供最好的手性环境,并得到最佳结果(81%的产率和39%的ee)。The diversity synthesis of chiral phenanthrene ligands remains an important topic in the field of asymmetric catalysis.In this paper,using optically pure various substituted prolamides or hydroxyprolamides 1 as the chiral source,the intermediates 3 were synthesized by condensation cyclization with phenanthroline 2-formaldehyde 2.Then the nitrogen atom in the intermediates 3 were oxidized under the action of chloro perbenzoic acid,an oxidant,to provide 9 chiral phenanthroline-tertiary amine derived N-oxides 4a~4i in 32%~35%overall yield and dr 8/1~>20/1.The structures of products 4 were characterized by^(1)H NMR,^(13)C NMR and HR-MS(ESI-TOF).Furthermore,ligands 4a~4i can be applied in the metal-catalyzed asymmetric Friedel-Crafts alkylation reaction of indole 5 andβ,γ-unsaturatedα-keto ester 6.Among them,ligand 4i was able to provide a special chiral environment and led to best results(81%yield and 39%ee).

关 键 词：手性叔胺N-氧化物 手性菲咯啉配体 羟脯氨酰胺 菲咯啉-2-甲醛 合成 

分 类 号：O626.13[理学—有机化学] O623.7[理学—化学]