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Synlett 2006(16): 2569-2572  
DOI: 10.1055/s-2006-950443
LETTER
© Georg Thieme Verlag Stuttgart · New York

Ion-Supported Chiral Pyrrolidines as Enantioselective Catalysts for Direct Michael Addition of Nitroalkenes in [BMIm]PF6

Danqian Xu, Shuping Luo, Huadong Yue, Liping Wang, Yunkui Liu, Zhenyuan Xu*
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology, Hangzhou, 310014, P. R. of China
Fax: +86(571)88320066; e-Mail: greenchem@zjut.edu.cn ;
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Publication History

Received 31 May 2006
Publication Date:
22 September 2006 (online)

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Abstract

Imidazolium-supported-pyrrolidine-catalyzed asymmetric Michael addition reactions of unmodified ketones and aldehydes to nitroalkenes were performed in [BMIm]PF6 to give products in up to 98% yield and 99% enantioselectivity. The catalytic system presented a synergistic effect in the improvement of reaction per­formance and could be recycled.

Key words

imidazolium-supported pyrrolidine - asymmetric Michael reaction - nitroalkenes - ketones - aldehydes - ionic liquids

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Experimental Procedure for the Synthesis of Ion-Supported Chiral Pyrrolidines: A mixture of N-alkyl-imidazole (11 mmol) and (S)-(+)-2-bromomethylpyrrol-idine hydrobromide (3; 2.50 g, 10 mmol) in MeCN (30 mL) was heated with stirring at 80 °C for 8 h. After completion, the solvent was removed by distillation, and the residue was neutralized by NaOH and recrystallized in EtOH to afford the imidazolium-supported pyrrolidine 4a or 4b as a colorless solid. The mixture of 4a or 4b (7 mmol), AgBF4 or KPF6 (7 mmol), and MeCN-H2O (20 mL) was stirred at r.t. Solvents of the mixtures were distilled and evaporated under vacuum. The residue was then dissolved in MeOH-acetone to let the inorganic salts precipitate, which were then filtered off. After evaporating the solvents, the desired imidazolium-supported pyrrolidines 5a-d were obtained.

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Data of 4a: Solid; mp 141-143 °C; [α]D 20 6.5 (c = 2, EtOH). 1H NMR (400 MHz, DMSO-d 6): δ = 1.69-1.74 (m, 1 H), 1.90-1.94 (m, 1 H), 2.00-2.01 (m, 1 H), 2.10-2.14 (m, 1 H), 3.16-3.21 (m, 1 H), 3.26-3.31 (m, 1 H), 3.90 (s, 3 H), 3.99-4.03 (m, 1 H), 4.62-4.67 (m, 2 H), 7.80 (s, 1 H), 7.91 (s, 1 H), 9.29 (s, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 23.133, 27.779, 36.390, 45.139, 49.012, 59.257, 122.854, 124.197, 137.572. IR (film): 3403, 3133, 2944, 2873, 1566, 1412 cm-1. MS (ESI+): m/z (%) = 166 [M - Br]+. MS (ESI-): m/z (%) = 80 [Br]-. HRMS (ESI+): m/z calcd for [C9H16N3]+: 166.1339; found: 166.1338. Data of 4b: Solid; mp 128-131 °C; [α]D 20 5.5 (c = 2, EtOH). 1H NMR (400 MHz, DMSO-d 6): δ = 1.40 (t, J = 7.4 Hz, 3 H), 1.78-1.81 (m, 1 H), 1.83-2.20 (m, 3 H), 3.15-3.18 (m, 1 H), 3.25-3.36 (m, 1 H), 4.07 (m, 1 H), 4.23 (t, J = 7.4 Hz, 2 H), 4.71-4.73 (m, 2 H), 7.94 (d, 2 H), 9.41 (s, dr, 1 H, NH), 9.44 (s, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 15.165, 22.928, 27.654, 44.667, 44.942, 48.738, 59.088, 122.624, 122.878, 136.665. IR (film): 3425, 3133, 2941, 2717, 1563, 1450 cm-1. MS (ESI+): m/z (%) = 180 [M - Br]+. MS (ESI-): m/z (%) = 80 [Br]-. HRMS (ESI+): m/z calcd for [C10H18N3]+: 180.1495; found: 180.1494.

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Typical Procedure for the Michael Reaction: Cyclohexanone (3 mmol) was added to a solution of β-nitro-styrene (1.5 mmol) and imidazolium-supported pyrrolidine catalyst (0.3 mmol) in [BMIm]PF6 (4 mL). The mixture was stirred at r.t. until completion of the reaction was established by GC. The reaction mixture was then extracted with Et2O-EtOAc (1:1, 3 ×), the combined extract phases were dried (Na2SO4), concentrated and purified by preparative TLC (PE-CH2Cl2, 1:1) to afford the Michael adduct. The ee of the product was determined by chiral HPLC analysis. On the other hand, the left ion-supported pyrrolidine-[BMIm]PF6 system could be reused directly in subsequent reactions without further disposal.