Acta Chimica Sinica ›› 2021, Vol. 79 ›› Issue (6): 742-746.DOI: 10.6023/A21050198 Previous Articles     Next Articles



杨普苏a, 刘晨旭a, 张文文a,b, 游书力a,b,*()   

  1. a 中国科学院上海有机化学研究所 金属有机化学国家重点实验室 上海 200032
    b 华东师范大学 庄长恭研究所 上海 200062
  • 投稿日期:2021-05-08 发布日期:2021-06-11
  • 通讯作者: 游书力
  • 基金资助:
    国家自然科学基金(21821002); 国家自然科学基金(21961132002); 上海市科学技术委员会(19590750400)

Ir-Catalyzed Enantioselective Friedel-Crafts Type Allylic Substitution of Indolizines

Pusu Yanga, Chen-Xu Liua, Wen-Wen Zhanga,b, Shu-Li Youa,b()   

  1. a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
    b Chang-Kung Chuang Institute, East China Normal University, Shanghai 200062, China
  • Received:2021-05-08 Published:2021-06-11
  • Contact: Shu-Li You
  • Supported by:
    National Natural Science Foundation of China(21821002); National Natural Science Foundation of China(21961132002); Science and Technology Commission of Shanghai Municipality(19590750400)

Indolizine is an important N-containing heterocyclic nucleus and their derivatives display interesting biological activities. The development of synthetic methods towards indolizine derivatives has attracted extensive attention. Despite the rapid growth in this area, asymmetric synthesis of indolizine derivatives has been rarely reported. Ir-catalyzed asymmetric allylic substitution reaction is an efficient method for the enantioselective construction of C-C or C-X bonds, furnishing terminal olefins bearing a stereogenic center at the allylic position with excellent regio- and enantioselectivities. In this regard, various electron-rich arenes, including indoles, pyrroles, naphthols, have been applied as the nucleophiles via Friedel-Crafts type process in the allylic substitution reactions. As a class of constitutional isomers of indoles, indolizines are now demonstrated as suitable nucleophiles in transition-metal-catalyzed allylic substitution reactions. Herein, an iridium- catalyzed enantioselective allylic substitution of allylic alcohol with indolizine is reported. A broad range of 3-allylindolizines were accessed with high yields (83%~95%) and excellent enantioselectivities (95%~>99%ee). A general procedure for the asymmetric allylation of indolizines is described in the following: A flame-dried Schlenk tube was cooled to room temperature and filled with argon. To this flask were added [Ir(cod)Cl]2 (4.0 mg, 0.006 mmol, 3 mol%) and (S)-L1 (12.1 mg, 0.024 mmol, 12 mol%). After the flask was evacuated and refilled with argon for three times, freshly distilled dichloromethane (DCM) (2 mL) were added. After the mixture was stirred for 15 min at room temperature, indolizines (0.2 mmol, 1.0 equiv.), allylic alcohols (0.4 mmol, 2.0 equiv.) and (PhSO2)2NH (18.0 mg, 0.06 mmol, 30 mol%) were added under argon atmosphere. The reaction mixture was stirred at room temperature and monitored by thin-layer chromatography (TLC). Once indolizines were consumed, the reaction was diluted with water (5 mL), and the mixture was extracted with EtOAc (10 mL×3). The organic layer was collected, dried over Na2SO4 and then concentrated in vacuo to afford the crude product. This crude material was purified by column chromatography to afford the product.

Key words: iridium-catalyzed, allylic substitution reaction, enantioselectivity, indolizine, allylic alcohol