Asymmetric Synthesis of Nitrocyclopropanes Catalyzed by Chiral Primary Amines

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.

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

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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.