化学学报 ›› 2022, Vol. 80 ›› Issue (3): 255-258.DOI: 10.6023/A22010002 上一篇    下一篇

研究通讯

吲哚-环丙烷的分子内开环反应

郑龙a, 王丽佳a,b,c,*(), 唐勇a,*()   

  1. a 中国科学院上海有机化学研究所 中国科学院大学 金属有机化学国家重点实验室 上海 200032
    b 华东师范大学 化学与分子工程学院 上海分子治疗与新药创制工程中心 上海 200062
    c 华东师范大学 化学与分子工程学院 上海分子智造前沿科学中心 上海 200062
  • 投稿日期:2022-01-01 发布日期:2022-02-11
  • 通讯作者: 王丽佳, 唐勇
  • 作者简介:
    庆祝中国科学院青年创新促进会十年华诞.
  • 基金资助:
    国家自然科学基金(91956103); 国家自然科学基金(21772224)

Intramolecular Ring-opening of Indole-cyclopropanes

Long Zhenga, Lijia Wanga,b,c(), Yong Tanga()   

  1. a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, University of Chinese Academy of Sciences, Shanghai 200032, China
    b Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
    c Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
  • Received:2022-01-01 Published:2022-02-11
  • Contact: Lijia Wang, Yong Tang
  • About author:
    Dedicated to the 10th anniversary of the Youth Innovation Promotion Association, CAS.
  • Supported by:
    National Natural Science Foundation of China(91956103); National Natural Science Foundation of China(21772224)

本工作使用In(NTf2)3作为金属Lewis酸催化剂, 实现了吲哚-环丙烷分子内的亲核开环反应, 克服了脂肪族取代的环丙烷活性低、不易实现开环反应的难题. 利用该方法可以简单高效地构建吡咯并[1,2-a]-吲哚骨架结构的化合物. 该反应条件温和, 底物普适性广, 最终以15个反应实例, 高达96%收率得到一系列吡咯并[1,2-a]-吲哚化合物.

关键词: In(NTf2)3, 环丙烷, 亲核开环, 分子内反应, 吡咯并[1, 吡咯并[1,2-a]-吲哚

Donor-acceptor cyclopropanes as efficient three-carbon synthetic building blocks were widely employed in the synthesis of many natural products and complex drug molecules. However, the ring-opening of aliphatic substituted cyclopropanes, owing to their poor reactivity, usually suffers from the harsh reaction conditions such as strong Lewis acid, large amount of catalyst, high reaction temperature and so on. In this paper, In(NTf2)3 was found as a powerful Lewis acid to catalyze the intramolecular nucleophilic ring-opening reaction of donor-acceptor cyclopropane with indole. This reaction could be used to construct the pyrrolo[1,2-a]-indole framework structure in a facile way. This method could be conducted in mild reaction conditions with a broad substrate scope (15 examples), leading to the target products in up to 96% yield. The general procedure is as following: To a dry Schlenk tube in a glove box, was placed In(NTf2)3 (0.1 equiv.), 4 Å molecular sieve (50 mg) and a stir bar. The tube was capped and brought out of the glovebox. After connected to argon via a typical Schlenk line system, a solution of 1 (1.0 equiv.) in PhCl (1 mL) was added dropwise until the reaction was completed (monitored by thin-layer chromatography). Et3N was added to quench the reaction and the reaction mixture was filtered through a thin layer of silica gel and eluted with EtOAc (100 mL). After removal of the volatiles under reduced pressure, the residue was purified by flash chromatography over silica gel to afford the product. When indole substrate contains electron-withdrawing substituents, the reaction temperature needs to be increased to 100 ℃ to obtain the target product.

Key words: In(NTf2)3, cyclopropane, nucleophilic ring-opening, intramolecular reaction, pyrrolo[1, pyrrolo[1,2-a]-indole