Highly Efficient One-Pot Synthesis of 1,2-Dihydro-2-oxo-3-pyridine-carboxylate Derivatives by FeCl₃-Promoted [3+3] Annulation

Abstract

An efficient one-pot synthesis of 1,2-dihydro-2-oxo-3-pyridinecarboxylate derivatives starting from enones and ethyl ­cyanoacetate in moderate to good yields is described. This novel tandem [3+3] annulation method mediated by FeCl₃ involves Michael addition and ketone-nitrile annulation followed by aromatization-dehydrogenation. A plausible mechanism is also proposed.

Key words

ethyl cyanoacetate - 1,2-dihydro-2-oxo-3-pyridine­carboxylate - ferric chloride - [3+3] annulation

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13

General Procedure for Ethyl 1,2-Dihydro-2-oxo-3-pyridinecarboxylates 3a-l.
Enones 2a-l (2.5 mmol), ethyl cyanoacetate (2.5 mmol) and FeCl₃ (7.5 mmol) were dissolved in propionic acid (5.0 mL), and the mixture was refluxed for about 0.5 h (monitored by TLC). After cooling, the mixture was poured into 1.0 N HCl (30.0 mL), then extracted by CH₂Cl₂ (3 × 30.0 mL). The combined organic layer was washed successively with aq NaHCO₃ (30.0 mL) and H₂O (30.0 mL). The organic layer was dried (Na₂SO₄) and the solvent was removed by distillation. The crude products obtained were purified by flash column chromatography (EtOAc-PE, 1:3) to give ethyl 1,2-dihydro-2-oxo-3-pyridinecarboxylates 3a-l.