Acta Chimica Sinica ›› 2019, Vol. 77 ›› Issue (9): 879-883.DOI: 10.6023/A19050193 Previous Articles     Next Articles

Special Issue: 有机自由基化学



钱向阳, 熊鹏, 徐海超*()   

  1. 厦门大学化学化工学院 厦门 361005
  • 投稿日期:2019-05-25 发布日期:2019-07-01
  • 通讯作者: 徐海超
  • 基金资助:
    项目受国家自然科学基金(No. 21672178);中央高校科研业务费资助

Modular Synthesis of Functionalized 4-Quinolones via a Radical Cyclization Cascade Reaction

Qian, Xiangyang, Xiong, Peng, Xu, Hai-Chao*()   

  1. College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005
  • Received:2019-05-25 Published:2019-07-01
  • Contact: Xu, Hai-Chao
  • Supported by:
    Project supported by the National Natural Science Foundation of China(No. 21672178);Fundamental Research Funds for the Central Universities

4-Quinolones are structural motifs prevalent in natural products and biologically active compounds. However, it remains challenging to synthesize 4-quinolones that bears diverse substituents at 2- and 3-positions. Herein we report an efficient and modular method for the synthesis of 4-quinolones from easily available N-aryl-O-propargyl carbamates and CO. The reactions employ 2-iodoxybenzoic acid (IBX) as an oxidant to oxidize the N-H group of the carbamate to generate an amide radical, which undergoes radical cyclization cascade with CO to afford the 4-quinolone product. The reactions provide speedy access to a series of 2,3-disubstituted 4-quinolones by varying the substituents of the carbamate substrate. Late stage functionalization employing Ni-catalysis allows the conversion of an OMe group on the 4-quinonone benzene ring to alkyl substituents, further increasing the diversity of the 4-quinone product. The synthetic potential is further demonstrated by running the synthesis on gram scale and by preparation of an enantiomerically enriched 4-quinolone product. The typical procedure is detailed as follows: A magnetic stirring bar, the carbamate substrate (0.25 mmol), IBX (1.0 mmol), and anhydrous dimethyl sulfoxide (DMSO, 10 mL) were placed in a 50 mL stainless steel autoclave. The autoclave was sealed, vacuumed and purged five times with CO, and finally pressurized with 10 MPa of CO. The reaction vessel was heated at 90 ℃ for 12 h and then cooled to r.t.. Excess CO was released in a fume hood. The reaction mixture was diluted with ethyl acetate (20 mL) and 5% NaHCO3 (15 mL). The phases were separated. The aqueous phase was extracted with ethyl acetate (20 mL×2). The combined organic solution was washed with 5% NaHCO3 (20 mL) and brine (20 mL). The organic solution was dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The residue was chromatographed through silica gel eluting with ethyl acetate/hexanes to give the desired product.

Key words: radical, cyclization, 4-quinolone, oxidation