A Nonoxidative Passerini Pathway to α-Ketoamides

Abstract

The Passerini adducts of cinnamaldehyde derivatives may be efficiently converted into α-ketoamides when heated with a base under microwave conditions.

Key words

Passerini - isocyanide - α-ketoamide

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• 14 Typical Procedure for 2a: The Passerini adduct 1a (102 mg, 0.338 mmol) and Cs₂CO₃ (1.0 equiv, 110 mg) were suspended in trifluoroethanol (TFE; 3.0 mL) in a 10-mL reaction glass vial containing a magnetic stir bar. The vial was flashed with argon, sealed and irradiated with stirring (CEM Discover Microwave. Settings: 140 °C, 150 W) during 15 min. Upon completion of the reaction time, the vial was cooled to r.t. The reaction mixture was diluted with H₂O (30 mL) and extracted with CH₂Cl₂ (3 × 15 mL). Purification by flash column chromatography on silica gel (CH₂Cl₂–petroleum ether, 20:80) gave 2a as a white solid (mp 86.0–86.5 °C) isolated in 93% yield (81 mg); R_f 0.6 (CH₂Cl₂–petroleum ether, 80:20). ¹H NMR (400 MHz, CDCl₃): δ = 7.26–7.30 (m, 2 H, H-Ar), 7.17–7.22 (m, 3 H, H-Ar), 6.82 (d, J = 6.3 Hz, 1 H, NH), 3.67–3.77 (m, 1 H), 3.28 (t, J = 7.5 Hz, 2 H), 2.93 (t, J = 7.5 Hz, 2 H), 1.87–1.91 (m, 2 H, H-Cy), 1.60–1.76 (m, 3 H, H-Cy), 1.32–1.42 (m, 2 H, H-Cy), 1.13–1.25 (m, 3 H, H-Cy). ¹³C NMR (100.6 MHz, CDCl₃): δ = 198.8, 159.0, 140.5, 128.6, 128.5, 126.3, 48.4, 38.4, 32.7, 29.2, 25.4, 24.8. HRMS: m/z calcd for C₁₆H₂₁NO₂: 259.1572; found: 259.1564. IR (CHCl₃): 3398, 2938, 2858, 1720, 1682, 1522, 1498, 1453, 1373, 1116, 892 cm^–1.
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