有机催化吲哚碳环上的不对称Friedel-Crafts烷基化反应  

Organocatalyzed Asymmetric Friedel-Crafts Alkylation in the Carbocyclic Ring of Indole

作　　者：穆宏文 吴昊 高莹莹 金瑛 王黎明 MU Hongwen;WU Hao;GAO Yingying;JIN Ying;WANG Liming(Department of Pharmacy,Jilin Medical University,Jilin 132013,China;Department of Pharmacy,Yanbian University,Yanji 133000,China)

机构地区：[1]吉林医药学院药学院,吉林132013 [2]延边大学药学院,延吉133000

出　　处：《高等学校化学学报》2022年第2期47-55,共9页Chemical Journal of Chinese Universities

基　　金：吉林省科技厅自然科学基金项目(批准号:20190201077JC);吉林省教育厅“十三五”科学技术项目(批准号:JJKH20200450KJ);吉林省卫生与健康技术创新项目(批准号:2020J074);国家级大学生创新创业训练计划(批准号:202013706018)资助。

摘　　要：将金鸡纳碱衍生物双功能催化剂用于有机催化羟基吲哚与靛红的不对称Friedel-Crafts反应,筛选出最佳反应条件:催化剂为5%(摩尔分数)6′-脱甲基奎尼丁(1b),溶剂为四氢呋喃,反应温度0℃.以67%~91%的产率和最高达97%的对映选择性获得了苯环上取代的羟基烷基化产品.拓宽了该反应的催化剂类型和底物范围.The indole scaffolds are privileged skeletons widely found in many bioactive natural products,pharmaceuticals,and material molecules.Indoles show a high nucleophilic reactivity in the azole ring,which preferentially reacts with electrophilic aromatic substitution at the C3 position.However,the methods for the enantioselective functionalization of the indole benzene ring are scarce.When hydroxylindoles as nucleophiles have been used in the Friedel-Crafts reaction,the regioselective hydroxyalkylation happens in the indole carbocyclic ring due to the advantage of the directing and activating properties of the OH group.Furthermore,the four regioisomeric hydroxylindoles lead to functionalize regioselective every position of the indole benzene ring.In this paper,Cinchona alkaloid derivatives were used to organocatalyze the enantioselective Friedel-Crafts reaction of hydroxylindoles with isatins.The effect of solvent,temperature and catalyst loading were investigated.The optimized conditions were determined to be tetrahydrofuran(THF)as the solvent with a 5%(molar fraction)loading of catalyst 1b at 0℃.The four regioisomeric hydroxylindoles(4-OH,5-OH,6-OH and 7-OH indoles)and the different substituted isatins were evaluated to explore the scope and general applicability of this reaction.The resulting products were obtained in good yields(67%-91%)with up to 97%e.e.and excellent regioselectivities(>15∶1).The enantioselectivities were obviously affected by the position of hydroxyl group.When 4-OH indoles as nucleophiles reacted with 12 isatins,the main C5 substituted products were achieved with moderate to excellent stereoselectivities.The most reaction of 5-OH indoles got the main product of C4 position substitution with more than 80%e.e..When 6-OH and 7-OH indoles reacted with isatins,the excellent regioselectivities were observed.Only C5 substituted products with 88%-93%e.e.were obtained in the reaction of 6-OH indoles,and only C6 substituted products with middle enantioselectivities(72%-78%)were achieved with 7-OH in

关 键 词：金鸡纳碱衍生物 不对称催化 FRIEDEL-CRAFTS反应 羟基吲哚 靛红 

分 类 号：O643[理学—物理化学]