Synthesis of Tetrahydropyrrolo[1,2-a]quinoxalines and Tetrahydro­pyrido[1,2-a]quinoxalines via a One-Pot CuI-Catalyzed Aryl Amination-Hydrolysis-Condensation Process

Abstract

CuI-catalyzed coupling of 2-halotrifluoroacetanilides with l-proline or pipecolinic acid in DMSO at 90-110 ˚C followed by in situ hydrolysis at 100 ˚C afforded tetrahydropyrrolo[1,2-a]quinoxalines or tetrahydropyrido[1,2-a]quinoxalines.

Key words

catalysis - coupling - heterocycle - quinoxaline - one-pot process

References and Notes

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9

General Procedure for the Synthesis of Quinoxaline Derivatives: A Schlenk tube was charged with 2-iodo-trifluoroacetanilide (0.5 mmol), CuI (10 mg, 0.02 mmol), l-proline (or pipecolinic acid) (1.5 mmol), and K₂CO₃ (1.0 mmol) (for bromide, Cs₂CO₃ was used). The tube was evacuated and backfilled with argon. DMSO (4 mL) was added into the tube. The reaction mixture was stirred at 90 ˚C (for bromide, 110 ˚C) for 10-24 h. Then H₂O (3 mL) was added and the reaction mixture was stirred at 100 ˚C for 8-12 h. After the reaction mixture was cooled, sat. NH₄Cl (10 mL) solution was added. The mixture was extracted with EtOAc and the organic layer was washed with H₂O, brine and dried over Na₂SO₄. After concentration in vacuo, the residue was purified by column chromatography on silica gel (eluting with 6:1 → 4:1 PE-EtOAc) to provide the desired product.