有机催化3-氨基氧化吲哚与偶氮二羧酸酯的不对称加成反应  

Organocatalyzed Asymmetric Addition of 3-Aminoxindole with Azodicarboxylates

作　　者：张健[1,2] 田芳 王立新[1] ZHANG Jian;TIAN Fang;WANG Lixin(Chengdu Institute of Organic Chemistry,Chinese Academy of Sciences,Chengdu 610000,China;University of Chinese Academy of Sciences,Beijing 100000,China)

机构地区：[1]中国科学院成都有机化学研究所,四川成都610000 [2]中国科学院大学,北京100000

出　　处：《合成化学》2024年第2期116-123,共8页Chinese Journal of Synthetic Chemistry

基　　金：国家重点研发计划项目(2021YFC2102100)。

摘　　要：手性3,3-双取代氧化吲哚结构单元广泛存在于具有生物活性的天然产物和具有药物活性的化合物中,尤其存在于具有光学活性的3-氨基氧化吲哚中。此外,手性3,3-双取代氧化吲哚结构单元作为有效抗疟药(NITD609)、高效焦虑和抑郁抑制剂(SSR149415)以及HIV蛋白酶抑制剂而备受关注。因此,发展合成手性3-氨基氧化吲哚的新方法具有重要意义。为了实现反应的敏感性产物N,N′-缩靛红衍生物的不对称合成,使用金鸡纳碱衍生的方酰胺作催化剂,3-氨基氧化吲哚席夫碱与偶氮二羧酸酯作模板底物,最终以70%~85%的产率和45%~88%的对映选择性获得相应产物。该反应的实验条件温和,原子经济性高。Chiral 3,3-disubstituted oxyindole structural units are widely found in biologically active natural products and pharmaceutically active compounds,especially in optically active 3-aminoindole oxides.In addition,the chiral 3,3-disubstituted oxyindole structural unit has attracted much attention as an effective antimalarial drug(NITD609),a highly effective anxiety and depression inhibitor(SSR149415),and an HIV protease inhibitor.Therefore,it is of great significance to develop new methods for the synthesis of chiral 3-aminoindole.In order to realize the asymmetric synthesis of N,N′-condensed isatin derivatives,which are sensitive products of the reaction,cinchona base-derived squaramides were used as catalysts,and 3-aminooxidized indole Schiff base and azodicarboxylic acid ester were used as catalysts.Template substrate,the corresponding product was finally obtained with a yield of 70%~85%and an enantioselectivity of 45%~88%.The results show that the experimental conditions of this reaction are mild and the atom economy is high.

关 键 词：N N′-缩靛红 不对称催化 3-氨基氧化吲哚席夫碱 偶氮二羧酸酯 亲电加成 

分 类 号：O621.2[理学—有机化学]