Synthesis of Multisubstituted Tetrahydroquinolines through Aza-Michael/ Michael Addition Catalyzed by Quaternary Ammonium Salt

Abstract

Multisubstituted tetrahydroquinolines were obtained in excellent yield from an array of N-[2-(3-oxo-3-phenylprop-1-enyl)phenyl]benzamide derivatives in a reaction catalyzed by quaternary ammonium salt. This method provides an efficient approach to the synthesis of densely substituted tetrahydroquinoline derivatives.

Key words

quaternary ammonium salt - tetrahydroquinolines - ­Michael addition - heterocycles

• References and Notes

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• 17 Synthesis of 6a; Typical Procedure: A mixture of 5a (32.7 mg, 0.01 mmol), K₃PO₄ (84.9 mg, 0.04 mmol), and BnEt₃NCl (2.28 mg, 0.001 mmol) in toluene (4 mL) was stirred at room temperature for 6 h. Upon completion of reaction as indicated by TLC, the solvent was evaporated and the residue was purified by flash chromatography on silica gel to provide the desired product 6a. ¹H NMR (400 MHz, CDCl₃): δ = 10.47 (s, 1 H), 7.98 (dd, J = 11.9, 4.7 Hz, 4 H), 7.89 (d, J = 8.1 Hz, 1 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.52–7.43 (m, 6 H), 67.43–7.37 (m, 1 H), 7.37–7.27 (m, 4 H), 7.27–7.12 (m, 6 H), 7.09 (d, J = 7.6 Hz, 1 H), 7.00 (dd, J = 11.1, 4.1 Hz, 1 H), 6.93 (t, J = 7.4 Hz, 1 H), 6.68 (d, J = 7.0 Hz, 1 H), 6.39 (d, J = 7.8 Hz, 1 H), 6.15 (d, J = 6.9 Hz, 1 H), 4.41 (dd, J = 11.4, 6.9 Hz, 1 H), 4.26 (t, J = 9.0 Hz, 1 H), 3.63 (dd, J = 18.1, 8.7 Hz, 1 H), 3.43 (dd, J = 18.1, 2.7 Hz, 1 H); ¹³C NMR (100 MHz, CDCl₃): δ = 200.05, 197.45, 170.36, 165.29, 138.67, 136.52, 136.32, 136.27, 135.52, 134.70, 134.43, 133.88, 133.49, 132.59, 131.40, 130.83, 129.17, 128.77, 128.68, 128.50, 128.44, 128.06, 128.01, 127.44, 127.38, 126.96, 126.81, 126.49, 125.66, 125.21, 125.06, 58.14, 55.14, 37.67, 34.79; IR (KBr): 3269, 3059, 2904, 1673, 1597, 1449, 1361, 1226, 972, 755 cm^–1; MS (ESI): m/z = 655 [M + H⁺]; HRMS (ESI): m/z [M + H⁺] calcd. for C₄₄H₃₅N₂O₄ ⁺: 655.2586; found: 655.25913.