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Synlett 2010(2): 266-270  
DOI: 10.1055/s-0029-1218570
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Synthesis of Nitrocyclopropanes Catalyzed by Chiral Primary Amines

Li-ting Dong, Quan-sheng Du, Chun-liang Lou, Jun-min Zhang, Rui-jiong Lu, Ming Yan*
Industrial Institute of Fine Chemicals and Synthetic Drugs, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. of China
Fax: +86(20)39943049; e-Mail: yanming@mail.sysu.edu.cn;
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Publication History

Received 14 September 2009
Publication Date:
11 December 2009 (online)

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Abstract

Asymmetric conjugate addition of bromonitromethane to α,β-unsaturated ketones was studied using a series of chiral primary amines as the catalysts. The cascade intramolecular cyclopropanation provided nitrocyclopropanes efficiently. Excellent enantioselctivities and good yields were obtained for several cyclic enones catalyzed by a bifunctional thiourea-primary amine. Both acid and base additives were found to be necessary for the transformation.

Key words

asymmetric conjugate addition - bromonitromethane - α,β-unsaturated ketone - nitrocyclopropane - organocatalysis

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17

Typical Procedure for the Conjugate Addition of Bromonitromethane to α,β-Unsaturated Ketones
Catalyst 1e (24 mg, 0.05 mmol), PhCOOH (6 mg, 0.05 mmol), and cyclohex-2-one (2a, 29 mg, 0.3 mmol) was dissolved in THF (0.5 mL). The solution was stirred at r.t. for 15 min. Then NMM (23 mg, 0.25 mmol) and bromonitro-methane (3, 35 mg, 0.25 mmol) was added, and the reaction mixture was stirred at r.t. for 24 h. The reaction solution was diluted with CH2Cl2 (5 mL) and washed with aq sat. NaHCO3 (3 mL). The organic layer was dried over anhyd Na2SO4. After the solvent was evaporated under vacuum, the residue was purified by flash column chromatography over silica gel (EtOAc-PE) to provide nitrocyclopropane 4a as a white solid.