摘要
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.
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 oxin-doles 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 Cl. 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 CH2C12 (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 CH2C12 was added slowly by a syringe pump in 20 minutes. The reaction was stirred at 0 °C till full consumption of 1 by TLC analysis. After the successive addition of Cl 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, VIV) as the eluent to give the desired spirocyclic oxindoles 5. The diastereoselectivities of 5 (>20:1) were determined by 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.
作者
廖富民
杜溢
周锋
周剑
Liao Fumin;Du Yi;Zhou Feng;Zhou Jian(Shanghai Key Laboratory of Green Chemistry and Chemical Processes,East China Normal University,Shanghai 200062;Xinhua Hospital,Affiliated to Shanghai Jiaotong University School of Medicine,Shanghai 200032;Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development,East China Normal University,Shanghai 200062;State Key Laboratory of Organometallic Chemistry,Shanghai Institute of Organic Chemistry,CAS,Shanghai 200032)
出处
《化学学报》
SCIE
CAS
CSCD
北大核心
2018年第11期862-868,共7页
Acta Chimica Sinica
基金
国家自然科学基金(No.21472049)资助~~
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
Au(I)/Chiral tertiary amine catalysis
diazooxindoles
trisubstituted monofluorinated enol silyl ethers
quaternary spirocyclic oxindoles
trisubstituted alkenes