Acta Chimica Sinica ›› 2019, Vol. 77 ›› Issue (11): 1168-1172.DOI: 10.6023/A19080303 Previous Articles     Next Articles



张硕a, 侯梓桐b, 宋子贺b, 苏晓峰a, 王峰a, 于一涛a, 彭丹a*(), 崔仕麒b, 刘一帆b, 王佳睿c, 宋建军b*()   

  1. a 齐鲁工业大学(山东省科学院) 山东省科学院新材料研究所 山东省特种含硅新材料重点实验室 济南 250014
    b 齐鲁工业大学(山东省科学院) 化学与制药工程学院 山东省分子工程重点实验室 济南 250353
    c 山东农业大学 食品科学与工程学院 泰安 271018
  • 投稿日期:2019-08-16 发布日期:2019-10-16
  • 通讯作者: 彭丹,宋建军;
  • 基金资助:

Zn/Ni Bimetallic Relay Catalysis: One Pot Intramolecular Cycloisomerization/Intermolecular Amidoalkylation Reaction toward Oxazole Derivatives

Zhang Shuoa, Hou Zitongb, Song Ziheb, Su Xiaofenga, Wang Fenga, Yu Yitaoa, Peng Dana*(), Cui Shiqib, Liu Yifanb, Wang Jiaruic, Song Jianjunb*()   

  1. a Shandong Provincial Key Laboratory for Special Silicone-Containing Materials, Advanced Materials Institute, Qilu University of Technology(Shandong Academy of Sciences), Jinan 250014, China
    b Shandong Provincial Key Laboratory of Molecular Engineering, School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology(Shandong Academy of Sciences), Jinan 250353, China
    c College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, China
  • Received:2019-08-16 Published:2019-10-16
  • Contact: Peng Dan,Song Jianjun;
  • Supported by:
    the Shandong Provincial Natural Science Foundation(2017YFC1600301);the Youth Science Funds of Shandong Academy of Sciences(2018QN0030);the National Natural Science Foundation of China(51503118)

Oxazole derivatives are widely found in natural products and pharmaceuticals with impressive biological properties, tremendous efforts have been devoted to the development of new methodologies and strategies to construct the oxazole rings. However, most of these reactions require harsh reaction conditions, limiting the wide application of these classical oxazole synthetic methods in organic synthesis. N-Acyliminium ions represent important electron deficient carbocations intermediates in organic synthesis because they provide various biologically important natural and unnatural products via C-C and C-heteroatom bondforming methodologies using an inter-or intramolecular path. The removal of a good leaving group at the α-position of amides or lactams usually generates N-acyliminium ions, which act as more electron-deficient carbocations toward nucleophiles. In this paper, a novel tandem metal relay catalytic system of Zn/Ni has been successfully developed. By using this unprecedented Zn(OTf)2/Ni(ClO4)2·6H2O bimetallic relay catalytic system, a variety of oxazole derivatives were obtained from easily available N-(propargyl)-arylamides and various γ-hydroxy lactams through intramolecular cycloisomerization/intermolecular amidoalkylation under mild conditions. The first step of the one-pot procedure is that Zn(OTf)2 acts as a π acid to activate the triple bond of N-(propargyl)-arylamides, and a subsequent intramolecular 5-exo-dig cyclization forms the oxazoline intermediate. Separately, Ni(ClO4)2·6H2O acts as Lewis acid to activate and facilitate the departure of 3-hydroxyl group to form the electrophilic acyliminium ions, which then in an intermolecular reaction is transformed to the oxazole derivatives in good to excellent yield. Control experiments in the optimization section disclose the fact that Zn(OTf)2 and Ni(ClO4)2·6H2O are both indispensable for this intramolecular cycloisomerization/intermolecular amidoalkylation reaction. Generally, the synthetic reactions run under air atmosphere by heating all the substrates and reagents in one-pot at 100℃. The N-(propargyl)-arylamide containing different types of electron-donating substituents, different electron-rich aromatic rings and different electron-withdrawing substituents can react with 3-hydroxy-2-benzyl-isoindolin-1-one to give the corresponding oxazole derivatives. In contrast, the propargyl amide containing an electron withdrawing group has a lower yield than the one using other propargyl amide, because the activity of the oxazoline intermediate obtained by the propargyl amide containing an electron withdrawing group is lower. 3-Hydroxy-2-phenylisoindoline-1-one, 3-hydroxy-2-phenylmethylisoindoline-1-one and 3-hydroxy-2-phenylethylisoindoline-1-one have also been found applicable to this reaction. The present method benefits from the distinctive features of simple reaction conditions, high atom economy and broad substrate tolerance. It is of great significance for the synthesis of oxazole derivatives and the formation of acyliminium ions.

Key words: relay catalysis, cycloisomerization, acyliminium ion, amidoalkylation reaction, oxazole derivatives