化学学报 ›› 2018, Vol. 76 ›› Issue (11): 862-868.DOI: 10.6023/A18060238 上一篇    下一篇

所属专题: 有机小分子-金属协同催化

研究通讯

Au(I)/手性双功能叔胺催化实现的一锅法串联成烯/不对称环化反应构建螺环季碳氧化吲哚

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
  • 收稿日期:2018-06-18 出版日期:2018-11-15 发布日期:2018-07-23
  • 通讯作者: 周剑 E-mail:jzhou@chem.ecnu.edu.cn
  • 基金资助:

    项目受国家自然科学基金(No.21472049)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 Online:2018-11-15 Published:2018-07-23
  • Contact: 10.6023/A18060238 E-mail:jzhou@chem.ecnu.edu.cn
  • Supported by:

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

研究报道了Au(I)/手性叔胺串联催化实现的一锅法不对称反应,实现从重氮氧化吲哚和氟代烯醇硅醚出发构建螺环季碳氧化吲哚.反应的第一步是3.0 mol% IPrAuBF4催化的重氮氧化吲哚与单氟烯醇硅醚的交叉偶联反应,现场产生N-Ac保护的3-烯基氧化吲哚在手性叔胺-四方酸C1的催化下与N-Ts邻氨基查尔酮再发生不对称Michael/Michael反应,以中等到良好的产率以及对映选择性,>20:1的非对映选择性得到螺环季碳氧化吲哚.反应的关键一步是Au(I)催化的给体-受体类重氮化合物与三取代单氟烯醇硅醚的成烯化反应,高效构建三取代烯烃.

关键词: Au(I)/手性叔胺催化, 重氮氧化吲哚, 三取代单氟烯醇硅醚, 螺环季碳氧化吲哚, 三取代烯烃

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