Copper-Mediated Synthesis of Aryl α-Keto Amides from Epoxide Derivatives

^◊ These authors contributed equally.

Abstract

A novel Cu^II-mediated synthesis of aryl α-keto amides from epoxide derivatives is reported. This transformation was conducted by using O₂ as a green oxidant that meets the requirements of sustainable chemistry.

Key words

copper catalysis - keto amides - epoxides - green chemistry

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• 10 α-Keto Amides 3a–l; General Procedure A mixture of the appropriate epoxide 1 (1.0 mmol) and Cu(OAc)₂ (2.0 mmol) in DMF (2.0 mL) was stirred overnight at 120 °C under O₂, then cooled to r.t. and diluted with EtOAc. H₂O was added, and the mixture was extracted with EtOAc. The organic layer was washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel). N,N-Dimethyl-2-oxo-2-phenylacetamide (3a) Colorless oil; yield: 133 mg (75%), R_f = 0.5 (EtOAc–PE, 1:3). ¹H NMR (400 MHz, CDCl₃): δ = 8.12–7.84 (m, 2 H), 7.72–7.57 (m, 1 H), 7.57–7.41 (m, 2 H), 3.08 (s, 3 H), 2.93 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 191.9, 167.2, 134.9, 133.2, 129.8, 129.1, 37.2, 34.1. N,N-Dimethyl-2-oxo-2-(4-tolyl)acetamide (3b) Colorless oil; yield: 124 mg (65%); R_f = 0.5 (EtOAc–PE, 1:3). ¹H NMR (400 MHz, CDCl₃): δ = 7.79 (d, J = 8.2 Hz, 2 H), 7.26 (d, J = 7.9 Hz, 2 H), 3.06 (s, 3 H), 2.90 (s, 3 H), 2.39 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 191.7, 167.4, 146.1, 130.8, 130.0, 129.9, 37.2, 34.1, 22.0.