7-氮杂吲哚去芳香化[3+2]环加成合成7-氮杂吲哚啉并[3,4-b]四氢吡咯骨架衍生物  

Dearomatization of 7-Azaindole Synthesis of Pyrrolo[3,4-b]-7-azaindole Derivatives through [3 + 2]Dipolar Cycloaddition

作　　者：王凯凯[1,2] 邓金根[1] 

机构地区：[1]中国科学院成都有机化学研究所,四川成都610041 [2]中国科学院大学,北京100049

出　　处：《精细化工》2016年第9期1023-1029,共7页Fine Chemicals

摘　　要：以7-氮杂吲哚为原料,经酰化和硝化得到3-硝基-1-酰基-7-氮杂吲哚衍生物Ⅰa^g,再由Ⅰa^g和原位产生的1,3-偶极子发生去芳香化[3+2]环加成反应得到7-氮杂吲哚啉并[3,4-b]四氢吡咯衍生物(Ⅲa^g),并对其合成条件进行了优化。在二氯甲烷作溶剂,室温反应1 h的条件下,Ⅲa^g的产率为85%~95%,非对映选择性dr>99∶1。目标化合物的结构经1HNMR、13CNMR和HR-MS进行了表征。此外,对目标产物(S,S)-6-苄基-4b-硝基-8-甲苯磺酰基-4b,5,6,7,7a,8-六氢吡咯并[3',4'∶4,5]吡咯并[2,3-b]吡啶(Ⅲa)进行了X射线衍射测试,对其晶体结构进行了分析,结果表明,Ⅲa的两个手性中心为(S,S)构型或者(R,R)构型。3-Nitro-l-acyl-7-azaindole derivatives （ I a -g） were obtained by the acylation and nitration of 7-azaindole. The [3 ＋ 2 ] cycloaddition of 3-nitro-l-acyl-7-azaindole derivatives and 1, 3-dipole afforded hexahydropyrrolo [ 3,4-b ] -7-azaindole derivatives （ Ⅲa ~ g ）. The synthetic conditions of hexahydropyrrolo [3,4-b ]-7-azaindole derivatives were optimized. Ⅲa-g had a yield of between 85% and 95% and their diastereoselectivity was more than 99：1 when the reaction was carried out in methylene chloride at room temperature for 1 h. The structure of the resulting compounds was characterized by 1HNMR, 13CNMR and high resolution mass spectrometry （HR-MS）. The results showed that the structure of the target products were consistent with that of the designed compounds. Furthermore, X-ray diffraction was used to analysis the crystalline structure of compound （S, S）-6- benzyl-4b-nitro-8-tosyl-4b, 5,6,7,7 a, 8-hexahydropyrrolo [ 3＇,4 ＇：4,5 ] pyrrolo [ 2,3-b ] pyridine （ Ⅲ a）. The result showed that compound Ⅲa had the relative configuration of （S,S） or （R,R） with two chiral centers.

关 键 词：7-氮杂吲哚 去芳香化 非对映选择性 环加成 医药与日化原料 

分 类 号：O625[理学—有机化学]