Synthesis of 4-Quinolones through Nickel-Catalyzed Intramolecular Amination on the β-Carbon of o-(N-Alkylamino)propiophenones

Abstract

o-(N-Alkylamino)propiophenones are converted into 4-quinolones in the presence of chlorobenzene, potassium phosphate, morpholine, and nickel(0) catalyst. The reaction proceeds through the nickel-catalyzed formation of β-enaminones from o-(N-alkylamino)propiophenones and morpholine, followed by the intramolecular transamination.

Key words

nickel - cyclization - amination - ketones - oxidation

• References


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• 10 Typical Procedure for the Transformation of 1a into 2a In a nitrogen-filled drybox, a 4 mL screw-capped vial was charged with Ni(cod)₂ (5.6 mg, 0.020 mmol), K₃PO₄ (424.5 mg, 2.0 mmol), and DMF (0.2 mL). After a magnetic stir bar was added, the vial was fitted with a septum cap and removed from the drybox. A solution of trimethylphosphine in THF (60 μL, 1 M solution, 0.060 mmol), chlorobenzene (0.20 mL, ρ = 1.106 g/mL, 1.97 mmol), o-(N-methylamino)-propiophenone (1a, 81.3 mg, 0.50 mmol), and morpholine (4.5 μL, ρ = 0.996, 0.05 mmol) were added. The resulting mixture was heated at 100 °C for 48 h. The reaction mixture was filtered through a Celite pad to remove the insoluble inorganic salt. The filtrate was concentrated and purified by silica gel column chromatography (EtOAc–MeOH = 5:1) to give 4-quinolone 2a (69.1 mg, 87%) as a pale yellow solid. ¹H NMR (400 MHz, CDCl₃, TMS): δ = 3.81 (s, 3 H), 6.28 (d, J = 7.7 Hz, 1 H), 7.37–7.48 (m, 2 H), 7.51 (d, J = 7.7 Hz, 1 H), 7.69 (ddd, J = 8.7, 7.1, 1.6 Hz, 1 H), 8.48 (dd, J = 8.2, 1.6 Hz, 1 H). ¹³C{¹H} NMR (100 MHz, CDCl₃): δ = 40.6, 109.9, 115.3, 123.7, 126.7, 126.9, 132.1, 140.5, 143.7, 178.2