Acta Chimica Sinica ›› 2020, Vol. 78 ›› Issue (3): 245-249.DOI: 10.6023/A20010019 Previous Articles     Next Articles



张荣华a, 许冰a, 张展鸣b, 张俊良a,b   

  1. a 华东师范大学化学与分子工程学院 上海市绿色化学与化工过程绿色化重点实验室 上海 200062;
    b 复旦大学化学系 上海 200438
  • 投稿日期:2020-01-21 发布日期:2020-03-09
  • 通讯作者: 张展鸣, 张俊良;,
  • 基金资助:

Ming-Phos/Copper(I)-Catalyzed Asymmetric[3+2] Cycloaddition of Azomethine Ylides with Nitroalkenes

Zhang Ronghuaa, Xu Binga, Zhang Zhanmingb, Zhang Junlianga,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 Department of Chemistry, Fudan University, Shanghai 200438
  • Received:2020-01-21 Published:2020-03-09
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 21425205, 21672067, 21801078), 973 Program (No. 2015CB856600), and the Program of Eastern Scholar at Shanghai Institutions of Higher Learning and the China Postdoctoral Science Foundation (Nos. 2019M650071, 2019M661418).

Optically pure pyrrolidine ring systems are core structural motifs found in a range of bioactive compounds, natural products, pharmaceuticals and catalysts. The synthesis of optically pure pyrrolidine ring systems is no longer mysterious as a great number of studies concerning the catalytic asymmetric 1,3-dipolar cycloaddition of iminoesters have been reported. Overall, the transition-metal-catalyzed asymmetric 1,3-dipolar cycloaddition of iminoesters with electron-deficient alkenes is one of the most powerful and straightforward synthetic tools for the optically pure pyrrolidines. However, high diastereo-and enantioselectivities are requested simultaneously during the synthesis of chiral substituted pyrrolidine and it still remains a big challenge to develop an efficient way to achieve both of them. Recently, we developed a novel chiral sulfinamide mono-phosphine (Ming-Phos) which performed well in copper-catalyzed intermolecular cycloaddition of iminoesters with β-trifluoromethyl β,β-disubstituted enones or α-trifluoromethyl α,β-unsaturated esters. Encouraged by the satisfying results, herein we report the Ming-Phos/Cu-catalyzed asymmetric intermolecular[3+2] cycloaddition of azomethine ylides with nitroalkenes. To our delight, a new Ming-Phos M3 bearing a trifluoromethyl showed good performance in this type of inter-molecular cycloaddition with high diastereo-and enantioselectivities (up to 13:1 dr, 98% ee and 95% yield). High efficiency, high diastereo-and enantioselectivity, a novel ligand, an inexpensive copper catalyst, and good functional group tolerance make it worth to be considered as an efficient, reliable and atom-economic strategy for the synthesis of optically pyrrolidines. The general procedure is as following:the solution of M3 (5.5 mol%) and Cu(CH3CN)4BF4 (5 mol%) in methyl tert-butyl ether (MTBE, 6 mL) was stirred at room temperature for 2 h. After the reaction temperature was dropped to -30℃, azomethine ylides 2 (0.6 mmol), Cs2CO3 (0.15 mmol) and nitroalkene 1 (0.3 mmol) were added sequentially. After the nitroalkene 1 was consumed completely, the solvent was removed under reduced pressure. The crude product was analyzed with 1H NMR to determine the diastereomeric ratio. Then the crude product was then purified by flash column chromatography on silica gel to afford the desired product.

Key words: copper catalysis, phosphine ligand, cycloaddition, enantioselectivity, ylides