Acta Chim. Sinica ›› 2015, Vol. 73 ›› Issue (7): 685-689.DOI: 10.6023/A15040235 Previous Articles     Next Articles



尹小平a, 徐鹏巍a, 董坤a, 廖奎a, 周锋a, 周剑a,b   

  1. a 华东师范大学化学与分子工程学院 绿色化学与化工过程绿色化上海市重点实验室 上海 200062;
    b 中国科学院上海有机化学研究所 金属有机国家重点实验室 上海 200032
  • 投稿日期:2015-04-07 发布日期:2015-05-15
  • 通讯作者: 周剑
  • 基金资助:

    项目受国家自然科学基金(Nos. 21172075, 21222204)资助.

Ga(OTf)3 Catalyzed Highly Efficient Substitution Reaction of 3-Hydroxyoxindoles Using TMSN3

Yin Xiaopinga, Xu Pengweia, Dong Kuna, Liao Kuia, Zhou Fenga, Zhou Jiana,b   

  1. a Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062;
    b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
  • Received:2015-04-07 Published:2015-05-15
  • Supported by:

    Supporting information for this article is available free of charge via the Internet at supported by the National Natural Science Foundation of China (Nos. 21172075, 21222204).

We report a highly efficient substitution reaction of 3-hydroxyoxindoles 1 using TMSN3 to furnish 3-substituted 3-azidooxindoles as the precursor of quaternary 3-aminooxindoles. Ga(OTf)3 is found to be the most efficient Lewis acid for this reaction, and catalyst loading could be lowered down to 1.0 mol%. Accordingly, under an nitrogen atmosphere, to a 10 mL Schlenk tube are successively added Ga(OTf)3 (0.05 mmol, 25.8 mg), 3-hydroxyoxindoles 1 (0.5 mmol) and 2.5 mL of acetonitrile, followed by the addition of TMSN3 (1.5 mmol, 207 μL). The resulting mixture is stirred at 25 ℃ till the full consumption of the 3-hydroxyoxindoles, monitored by TLC analysis. After the solvent is removed under reduced pressure, the residue is directly subjected to column chromatography, using an eluent of petroleum ether/ethyl acetate (10/1, V/V) as the eluent, to afford the desired products 3. Under this condition, a variety of differently substituted 3-aryl 3-hydroxyoxindoles 1a1m work well with TMSN3 to provide the corresponding 3-aryl 3-azidooxindoles 3a3m in good to excellent yield. 3-Methyl 3-hydroxyoxindoles 1n1o also react with TMSN3 to give the desired product 3n3o in good yield. But 3-allyl 3-hydroxyoxindole 1p reacts with TMSN3 poorly under this condition, affording product 3p in only 27% yield. These results indicate that this method has certain universality, but the reaction is influenced by the substituents to some extent. The reaction could be run on a gram-scale, as evidenced by the reaction of 3-hydroxyoxindole 1a and TMSN3 on a 6.0 mmol scale with 1.0 mol% Ga(OTf)3 at 60 ℃, giving 3-phenyl 3-azidooxindole 3a in 89% yield (1.41 gram). The product 3a can be converted to quaternary 3-aminooxindoles 4 in 60% yield at 50 ℃ by Pd-catalyzed hydrogenation. To understand the reaction mechanism, the optically active 3-allyl 3-hydroxyoxindole 1p (84% ee) is chosen to react with TMSN3 under the standard condition, which affords product 3p in racemic form. This result provides strong evidence that a prochiral intermediate is involved in the reaction. We tend to believe that the reaction is initiated by the dehydration of 3-hydroxyoxindole 1p to generate a reactive benzylic cation which will react with TMSN3 to give the desired product 3p.

Key words: Ga(OTf)3, substitution reaction, 3-hydroxyoxindoles, TMSN3, quaternary aminooxindoles