Synthesis of 3H-Pyrrolo[2,3-c]quinoline by Sequential I₂-Promoted Cyclization/Staudinger/Aza-Wittig/Dehydroaromatization Reaction

Abstract

A facile synthetic approach to access of 3H-pyrrolo[2,3-c]quinoline derivatives has been achieved by a sequential I₂-promoted cyclization/Staudinger/aza-Wittig/dehydroaromatization reaction. The targeted products were received in moderate to good yields (62–81%). The broad substrate scope and easy availability of the starting materials make this method a valuable tool for generating 3H-pyrrolo[2,3-c]quinoline products.

Key words

3H-pyrrolo[2,3-c]quinolines - I₂-promoted cyclization - aza-Wittig reaction - azides - dehydroaromatization

• References and Notes

• 1 These authors contributed equally.
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• 20 General Experimental Procedure for the Synthesis of 3H-Pyrrolo[2,3-c]quinolines To a solution of chalcone 3 (1 mmol), β-enamine ester (6, 1.5 mmol), K₂CO₃ (0.138 g, 1 mmol) in anhydrous DCE (5 mL) was added iodine (0.254 g, 1 mmol). The reaction was stirred at 80 °C for 10 h, and the reaction progress was monitored by TLC. Then, the mixture was washed with aqueous Na₂S₂O₃, dried with dry sodium sulfate, and the solvent was evaporated under reduced pressure to give the crude product dihydropyrrole intermediate 7. Afterwards, toluene (5 mL) and PPh₃ (0.262 g, 1 mmol) were added to the reaction system, and the mixture was heated to 110 °C for 12 h. After removal of the solvent under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate/petroleum ether = 1:8) to afford 3H-pyrrolo[2,3-c]quinolines 8a–q in 62–81% yield. Analytical Data for Compound 8a: White solid (yield 0.294 g, 75%), mp 212–214 °C. ¹H NMR (CDCl₃, 400 MHz): δ = 9.08 (d, J = 8.0 Hz, 1 H), 8.21 (d, J = 8.0 Hz, 1 H), 7.67–6.88 (m, 12 H), 4.07 (s, 3 H), 2.43 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 166.8, 147.8, 145.3, 143.5, 138.6, 137.1, 129.8, 128.7, 128.4, 127.8, 127.4, 127.3, 126.9, 125.8, 125.3, 122.1, 108.6, 51.7, 13.8. LC-MS: m/z = 392. Anal. Calcd for C₂₆H₂₀N₂O₂ (392.46): C, 79.57; H, 5.14; N, 7.14. Found: C, 79.54; H, 5.23; N, 7.09.