Ag₂O-Mediated Intramolecular Oxidative Coupling of Acetoacetanilides for the Synthesis of 3-Acetyloxindoles

Abstract

The intramolecular oxidative Csp^²-Csp^³ coupling of N-substituted acetoacetanilides was achieved by using Ag₂O as the oxidant. The reaction constitutes a convenient approach toward 3-acetyloxindoles from unfunctionalized acetoacetanilides.

3-acetyloxindoles - acetoacetanilides - Ag₂O - oxidative coupling

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15

General Procedure for the Reactions of 1 To a solution of 1 (0.5 mmol) in DMF (5 mL) was added Cs₂CO₃ (1.0 mmol) and Ag₂O (0.55 mmol). The mixture was stirred under argon at 50 ˚C for 7 h (or at 80 ˚C for 4 h). After the reaction was complete, the mixture was filtered though Celite and washed with EtOAc. The filtrate was added into sat. NH₄Cl solution and extracted with EtOAc for three times. The combined organic phase was washed with brine and dried with anhyd MgSO₄. The solvent was then removed under reduced pressure, and the residual was subjected to silica gel chromatography to give the product 2.

16

General Procedure for the Reactions of 3 To a solution of 3 (0.5 mmol) in DMF (10 mL) was added Cs₂CO₃ (1.0 mmol) and Ag₂O (0.55 mmol). The mixture was stirred under argon at 50 ˚C for 7 h (for 3a, the reaction temperature was 80 ˚C). After the reaction was complete, the mixture was filtered though Celite and washed with EtOAc. The filtrate was added into sat. NH₄Cl solution and extracted with EtOAc for three times. The combined organic phase was washed with brine and dried with anhyd MgSO₄. The solvent was then removed under reduced pressure, and the residual was subjected to silica gel chromatography to give the product 4.