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Synlett 2007(15): 2415-2419  
DOI: 10.1055/s-2007-985581
LETTER
© Georg Thieme Verlag Stuttgart · New York

Prolinol tert-Butyldiphenylsilyl Ether as Organocatalyst for the Asymmetric Michael Addition of Cyclohexanone to Nitroolefins

Fengying Liu, Shiwen Wang, Ning Wang, Yungui Peng*
School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, P. R. of China
Fax: +86(23)68254000; e-Mail: pyg@swu.edu.cn;
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Publication History

Received 4 June 2007
Publication Date:
13 August 2007 (online)

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Abstract

The direct Michael additions of cyclohexanone to nitro­olefins catalyzed by prolinol tert-butyldiphenylsilyl ether were ­conducted successfully in good yields (up to 99%) and high stereoselectivities (up to 98:2 diastereomeric ratio and 95% enantiomeric excess).

Key words

asymmetric - organocatalyst - Michael addition - cyclohexanone - nitroolefin

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Procedure for the Preparation of Catalyst 1a: To a DMF (10 mL) solution of prolinol (3.36 mmol) and imidazole (10.1 mmol) was added TBSCl (6.73 mmol) at 0 °C. The reaction mixture was stirred for 17 h at r.t. and quenched with aq NH4Cl and the organic materials were extracted with EtOAc and the combined organic phase was washed with brine. Then the organic extracts were dried over anhyd Na2SO4 and concentrated in vacuo after filtration. Purification by silica gel column chromatography gave (S)-2-[(tert-butyldimethylsilyloxy)methyl]pyrrolidine (1a) in 77% yield; [α]D r.t. -6.63 (c = 0.8, CHCl3). IR (neat): 3406, 2929, 2857, 2738, 1680, 1460, 1394, 1255, 1100, 840, 775 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.10-0.12 (d, J = 4.6 Hz, 6 H), 0.90 (s, 9 H), 1.84-1.89 (m, 1 H), 1.93-2.11 (m, 3 H), 3.29-3.38 (m, 2 H), 3.76-3.81 (m, 2 H), 3.94-3.98 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = -5.5, -5.3, 24.0, 25.8, 26.8, 45.7, 60.0, 62.1. Preparation of catalyst (S)-2-[(tert-butyldiphenylsilyloxy)methyl]pyrrolidine (1b) was similar to that of catalyst 1a. 1b: 85% yield; [α]D r.t. -5.8 (c = 0.94, CHCl3). IR (neat): 3419, 2935, 2866, 2734, 1112, 708, 504 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.09 (s, 9 H), 1.80-1.99 (m, 1 H), 2.02-2.04 (m, 3 H), 3.30-3.35 (t, J = 6.5 Hz, 2 H), 3.71-3.79 (m, 1 H), 3.83-3.84 (m, 1 H), 3.91-3.96 (m, 1 H), 7.39-7.73 (m, 10 H). 13C NMR (75 MHz, CDCl3): δ = 19.1, 23.8, 26.8, 45.6, 59.9, 63.0, 127.8, 129.9, 132.5, 135.6, 135.7.

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General Procedure for the Asymmetric Michael Addition of Cyclohexanone 2 to Nitroolefin 3 Catalyzed by 1b: The catalyst 1b (0.1 mmol) and cyclohexanone 2 (0.5 mL) were mixed in hexane (2 mL) at r.t. After stirring for 20 min and then cooling to 10 °C, the nitroolefin 3 was added. The mixture was stirred at 10 °C for the specified time (Table [2] ) and then directly purified by silica gel column chromatography (PE and EtOAc as the eluent) to obtain the product 4,17 which was confirmed by the comparison of IR, 1H NMR and 13C NMR data with that reported in the literature. The enantiomeric ratios were identified by HPLC analysis.

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(S)-2-[(R)-2-Nitro-1-phenylethyl]cyclohexanone (4): mp 125-126 °C; [α]D r.t. -26.1 (c = 1.42, CHCl3). IR (neat): 2958, 2929, 1699, 1551, 1495, 1448, 1384, 1129, 697 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.21-1.58 (m, 1 H), 1.62-1.75 (m, 4 H), 2.04-2.10 (m, 1 H), 2.38-2.47 (m, 2 H), 2.68 (m, 1 H), 3.72-3.80 (dt, J = 4.5, 9.9 Hz, 1 H), 4.53-4.66 (dd, J = 10.0, 12.3 Hz, 1 H), 4.91-4.97 (dd, J = 4.5, 12.4 Hz, 1 H), 7.15-7.17 (d, J = 6.9 Hz, 2 H), 7.23-7.34 (m, 3 H). 13C NMR (75 MHz, CDCl3): δ = 25.0, 28.5, 33.1, 42.7, 43.9, 52.5, 78.8, 127.7, 128.1, 128.9, 137.7, 211.9. HPLC condition: Chiralpak AD-H, λ = 254 nm, flow rate: 0.5 mL/min, eluent: hexane-i-PrOH (90:10), t and the paragraph.