Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (7): 867-872.DOI: 10.6023/A14040335 Previous Articles    

Special Issue: 不对称催化与合成



王雨卉, 曹中艳, 牛艳霏, 赵小莉, 周剑   

  1. 华东师范大学化学系 绿色化学与化工过程绿色化上海市重点实验室 上海 200062
  • 投稿日期:2014-04-28 发布日期:2014-05-14
  • 通讯作者: 周剑
  • 基金资助:


Highly Enantioselective Organocatalytic aza-Henry Reaction of Nitroalkanes to N-Boc Isatin Ketimines

Wang Yuhui, Cao Zhongyan, Niu Yanfei, Zhao Xiaoli, Zhou Jian   

  1. Department of Chemistry, East China Normal University, Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Shanghai 200062
  • Received:2014-04-28 Published:2014-05-14
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21172075, 21222204).

We report a highly enantioselective aza-Henry reaction of nitroalkanes with N-Boc isatin ketimines 1. A cinchona alkaloid derived bifunctional catalyst C5, featuring a C6 hydroxy group, is identified as a powerful catalyst for this reaction. Accordingly, under an atmosphere of nitrogen, to a 10 mL Schlenk tube are added C5 (0.03 mmol, 14.6 mg), MS5Å (120 mg), nitromethane (4.5 mmol, 244 μL) and 3.0 mL of toluene successively, followed by the addition of N-Boc isatin ketimine 1 (0.3 mmol). The resulting mixture is stirred at 20 ℃ till the full consumption of the ketimine, monitored by TLC analysis. After the solvent is removed under reduced pressure, the residue is directly subjected to column chromatography, using an eluent of dichloromethane and acetone (10:1, V/V), to afford the desired product 3. Under this condition, a variety of differently substituted N-Boc isatin ketimines work well with MeNO2 to provide the Mannich adduct in up to 91% ee. A 1.0 mmol scale reaction of 1a and MeNO2 is examined, giving adduct 3a in 87% yield and 90% ee. Unfortunately, unprotected isatin derived N-Boc isatin ketimine 1j provides the corresponding product in only 66% ee, suggesting the importance of the N-protecting group of isatin in securing high enantioselectivity. Nitroethane and nitropropane are also viable for this reaction, affording the corresponding products in high yield and excellent ee value, albeit with moderate diastereoselectivity.

Key words: organocatalysis, aza-Henry reaction, isatin ketimine, nitroalkane, quaternary aminooxindoles