化学学报 ›› 2014, Vol. 72 ›› Issue (7): 867-872.DOI: 10.6023/A14040335 上一篇    

所属专题: 不对称催化与合成

研究论文

高对映选择性的有机催化的硝基烷烃对N-Boc靛红亚胺的不对称aza-Henry反应

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
  • 收稿日期:2014-04-28 出版日期:2014-07-14 发布日期:2014-05-14
  • 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(Nos.21172075,21222204)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 Online:2014-07-14 Published:2014-05-14
  • Supported by:

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

研究实现了高对映选择性的硝基烷烃对N-Boc靛红亚胺1的不对称aza-Henry反应,来构建胺基季碳氧化吲哚. 发现在金鸡纳碱衍生的叔胺-酚羟基双功能催化剂C5的作用下,10种不同取代的N-Boc靛红亚胺与硝基甲烷的反应均能顺利进行,以66%~91%的对映选择性得到目标产物,产物的绝对构型通过X-ray单晶衍射加以确定. 硝基乙烷和硝基丙烷也能高对映选择性地参与反应,但非对映选择性不佳.

关键词: 有机催化, aza-Henry反应, 靛红亚胺, 硝基烷烃, 胺基季碳氧化吲哚

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