Easy Access to Quinolin-2(1H)-ones via a One-Pot Tandem Oxa-Michael–Aldol Sequence

Published as part of the ISHC Conference Special Section

Abstract

An efficient strategy for the synthesis of a variety of quinolin-2(1H)-one derivatives has been developed. The reaction proceeded from cinnamide derivatives via a tandem reaction in the presence of NaOH to afford the corresponding 2- quinolin-2(1H)-one derivatives in good to excellent yields.

Key words

quinolinone - tandem process - heterocycles - Michael addition - intramolecular aldol reaction

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• 12 Representative Procedure for Tandem Reaction To a solution of substrate 1a (75.0 mg, 0.22 mmol, 1 equiv) in a mixture of EtOH and H₂O (6 mL/3 mL, 2:1, 0.02 M) was added NaOH (35 mg, 0.87 mmol, 4 equiv) at r.t. The reaction mixture was stirred for 2 h at r.t. After completion, the reaction mixture was acidified with HCl (2 M) until pH = 7, and the solvent was remove under reduced pressure. The residue was then diluted in water, and the solution was extracted three times with EtOAc. The combined organic layers were washed with brine and dried with MgSO₄. The organic layer was evaporated under reduced pressure, and the crude product was purified by flash chromatography on silica gel (n-heptane/EtOAc = 7:3) to afford the corresponding pure product 2b as a yellow solid (54 mg, isolated yield 75%); mp 236–240°C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 11.87 (br s, 1 H), 9.33 (s, 1 H), 7.98 (s, 1 H), 7.91 (d, J = 2.6 Hz, 1 H), 7.49 (dd, J = 8.7, 2.4 Hz, 1 H), 7.28 (d, J = 8.7 Hz, 1 H), 7.16 (d, J = 8.7 Hz, 2 H), 6.68 (d, J = 8.6 Hz, 2 H), 5.42 (s, 1 H), 3.43 (qd, J = 7.0, 3.2 Hz, 2 H), 1.16 (t, J = 7.0 Hz, 3 H) ppm. ¹³C NMR (75 MHz, DMSO-d ₆): δ = 160.4 (C), 157.8 (C), 136.5 (C), 135.8 (C), 132.8 (CH), 130.8 (C), 129.6 (CH), 128.6 (2 CH), 127.0 (CH), 125.6 (C), 120.3 (C), 116.6 (CH), 114.8 (2 CH), 76.4 (CH), 63.6 (CH₂), 15.2 (CH₃) ppm. IR (neat): ν = 3188, 3100, 2965, 2881, 2679, 1893, 1765, 1646, 1612, 1594, 1571, 1516, 1491, 1450, 1414, 1373, 1329, 1313, 1268, 1245, 1229, 1205, 1173, 1153, 1127, 1107, 1085, 1057, 1005 cm^–1. ESI-HRMS (neg.): m/z [M – H]^–calcd for C₁₈H₁₅ClNO₃: 328.0740; found: 328.0750.