Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (11): 862-868.DOI: 10.6023/A18060238 Previous Articles     Next Articles

Special Issue: 有机小分子-金属协同催化



廖富民a, 杜溢b, 周锋a, 周剑a,c,d   

  1. a. 绿色化学与化工过程绿色化上海市重点实验室 华东师范大学化学与分子工程学院 上海 200062;
    b. 上海交通大学医学院附属新华医院 上海 200032;
    c. 上海分子治疗与新药创制工程技术研究中心华东师范大学化学与分子工程学院 上海 200062;
    d. 金属有机化学国家重点实验室 中国科学院上海有机化学研究所 上海 200032
  • 投稿日期:2018-06-18 发布日期:2018-07-23
  • 通讯作者: 周剑
  • 基金资助:


Au(I)/Chiral Tertiary Amine Catalyzed Tandem Olefination/Asymmetric Cyclization Reaction to Quaternary Spirocyclic Oxindoles

Liao Fumina, Du Yib, Zhou Fenga, Zhou Jiana,c,d   

  1. a. Shanghai Key Laboratory of Green Chemistry and Chemical Processes, East China Normal University, Shanghai 200062;
    b. Xinhua Hospital, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200032;
    c. Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, Shanghai 200062;
    d. State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, CAS, Shanghai 200032
  • Received:2018-06-18 Published:2018-07-23
  • Contact: 10.6023/A18060238
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21472049).

We report an asymmetric tandem reaction realized by sequential Au(I)/chiral bifunctional tertiary amine catalysis. A tandem olefination/asymmetric cyclization reaction is developed, allowing facile synthesis of quaternary spirocyclic oxindoles in good yields and stereoselectivities from N-Ac protected diazooxindoles 1, monofluorinated enol silyl ethers 2 and 2-tosylaminochalcone 4. The initial cross coupling reaction of diazooxindole and fluorinated enol silyl ethers, catalyzed by 3.0 mol% IPrAuBF4, readily afforded 3-alkenyloxindoles for the subsequent Michael/Michael addition of 2-tosylaminochalcone catalyzed by 5.0~10.0 mol% chiral bifunctional tertiary amine-squaramide C1. The tandem reaction was performed by the following general procedure. Under an atmosphere of N2, to an oven-dried Schlenk tube were added IPrAuCl (6.0 mg, 0.0099 mmol, 3.3 mol%) and AgBF4 (1.8 mg, 0.0090 mmol, 3.0 mol%), followed by anhydrous CH2Cl2 (1.0 mL). The resulting mixture was stirred at 25℃ for 0.5 h and then cooled down to 0℃. After ethers 2 (1.5 equiv.) was added in one-portion, a solution of diazooxindoles 1 in 1.5 mL of CH2Cl2 was added slowly by a syringe pump in 20 minutes. The reaction was stirred at 0℃ till full consumption of 1 by TLC analysis. After the successive addition of C1 and 4 (1.1 equiv.), the reaction was warmed to 25℃ and stirred till full consumption of 3, and the mixture was directly subjected to the column chromatography by using petroleum ether/dichloromethane (1/2.5, V/V) as the eluent to give the desired spirocyclic oxindoles 5. The diastereoselectivities of 5 (>20:1) were determined by 1H NMR analysis of the crude reaction mixture. The key step of this tandem sequence is the cross coupling reaction of monofluorinated enol silyl ethers and donor-acceptor diazo reagents. We further examined the substrates scope of acyclic aryl diazoacetates and fluorinated enol silyl ethers by using 1.0 mol% IPrAuSbF6 as catalyst, providing a new method for the efficient synthesis of trisubstituted alkenes.

Key words: Au (I)/Chiral tertiary amine catalysis, diazooxindoles, trisubstituted monofluorinated enol silyl ethers, quaternary spirocyclic oxindoles, trisubstituted alkenes