Acta Chimica Sinica ›› 2014, Vol. 72 ›› Issue (7): 856-861.DOI: 10.6023/A13121253 Previous Articles     Next Articles

Special Issue: 不对称催化与合成



谢明胜, 武晓霞, 王刚, 林丽丽, 冯小明   

  1. 四川大学 绿色化学与技术教育部重点实验室 化学学院 成都 610064
  • 投稿日期:2013-12-14 发布日期:2014-01-09
  • 通讯作者: 冯小明
  • 基金资助:

Catalytic Asymmetric [8+2] Cycloaddition for the Construction of Cycloheptatriene-Fused Pyrrolidin-3,3’-Oxindoles

Xie Mingsheng, Wu Xiaoxia, Wang Gang, Lin Lili, Feng Xiaoming   

  1. Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064
  • Received:2013-12-14 Published:2014-01-09
  • Supported by:
    Project supported by the National Basic Research Program of China (973 Program: No. 2011CB808600), the National Natural Science Foundation of China (Nos. 21321061, 21290182 and 21172151) and Ministry of Education (No. 20110181130014).

The spiro pyrrolidin-3,3'-oxindole core is a privileged skeleton that is found in many natural products and biologically active molecules. For its construction, the [3+2] cycloaddition of 2π component 3-alkenyl-oxindoles with 3π component azomethine ylides is one of the most effective strategies. Since the pioneering work of Gong and co-workers, great effort has been devoted to the development of asymmetric [3+2] cycloadditions with azomethine ylides as the dipole synthon, and impressive progress has been achieved. In contrast, there is no report about higher-order [8+2] cycloaddition of 3-alkenyl-oxindoles with azaheptafulvenes as the 8π dipole synthons, which is an effective way to build cycloheptatriene-fused pyrrolidin-3,3'-oxindole derivatives with three contiguous stereocenters, including a spiro-quaternary chiral carbon atom. Herein, the azaheptafulvenes is developed as a new dipole synthon with 3-alkenyl-oxindoles to construct pyrrolidin-3,3'-oxindoles derivatives for the first time. In the presence of 1 mol% of chiral N,N'-dioxide L6-Ni(Ⅱ) complex, the asymmetric [8+2] cycloaddition performs well, affording functionalized cycloheptriene-fused pyrrolidin-3,3'-oxindoles derivatives in excellent yields (90%~99%), diastereoselectivities (up to 97:3 dr), and enantioselectivities (92%~99% ee) under mild conditions. A representative procedure for the asymmetric [8+2] cycloaddition is as follows: to a test tube, the catalyst solution (1 mol%, in THF) was added, and the THF was evaporated by oil pump. N-Boc-3-alkenyl-oxindole 2a and 0.5 mL of CH2Cl2 were added sequentially under air (N2 atmosphere is not necessary). The reaction solution was stirred at 35 ℃ for 0.5 h, then the 8π component azaheptafulvene 1a (1.05 equiv.) was added. The mixture continued stirring at 35 ℃ until N-Boc-3-alkenyl-oxindole 2a was consumed (detected by TLC). Finally, the corresponding product 3a was purified by flash chromatography on basic Al2O3 [V(petroleum)/V(CH2Cl2)/V(EtOAc)=8:8:1].

Key words: chiral N,N'-dioxide, Ni(Ⅱ), [8+2] cycloaddition, spiro, asymmetric catalysis