Copper-Catalyzed One-Pot Oxidation–Aldol/Henry Reaction of Benzylic ­Amines to α,β-Unsaturated Methyl Ketone/Nitro Compounds

Abstract

A novel one-pot synthesis of α,β-unsaturated methyl ketone/nitro compounds from benzylic amines through an oxidation–aldol/Henry reaction is reported. The reaction proceeded well by using MCPBA as oxidant and CuCl₂·2H₂O as catalyst. A variety of functionalized α,β-unsaturated methyl ketone/nitro compounds were assembled in moderate yields by application of this catalytic one-pot reaction.

Key words

aldol reaction - amines - copper - condensation - oxidation

• References and Notes

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• 10 Oxidation–Aldol Reaction (Table 2); General Procedure: Under an argon atmosphere, to a solution of benzylamine (5 mmol) and CuCl₂·2H₂O (0.21 g, 1.25 mmol) in acetone (12 mL), MCPBA (1.12 g, 5.5 mmol) was added portionwise at 0 °C. The reaction mixture was heated at reflux in an oil bath with thorough stirring for 10 h (reaction monitored by TLC analysis). Upon cooling, saturated aqueous Na₂S₂O₃ (10 mL) was added to quench the reaction. The solvent was removed under reduced pressure and the residue was treated with 10% aq NaOH (15 mL) followed by extraction with EtOAc (3 × 10 mL). The combined extracts were washed with H₂O (5 mL) and brine (5 mL), and dried over anhydrous Na₂SO₄. Removal of the solvent under vacuum afforded the crude product, which was purified by column chromatography (hexane–EtOAc). Oxidation–Henry Reaction (Table 3); General Procedure: Under an argon atmosphere, to a solution of benzylamine (5 mmol) and CuCl₂·2H₂O (0.04 g, 0.25 mmol) in MeNO₂ (12 mL), MCPBA (1.12 g, 5.5 mmol) was added portionwise at 0 °C. The reaction mixture was stirred at 60 °C in an oil bath for 10 h (reaction monitored by TLC analysis). Upon cooling, saturated aqueous Na₂S₂O₃ (10 mL) was added to quench the reaction. The solvent was removed under reduced pressure and the residue was treated with 10% aq NaOH (15 mL) followed by extraction with EtOAc (3 × 10 mL). The combined extracts were washed with H₂O (5 mL) and brine (5 mL), and dried over anhydrous Na₂SO₄. Removal of the solvent under vacuum afforded the crude product, which was purified by column chromatography (hexane–EtOAc).