One-Pot Approach to Pyrido-4-phenanthridinones by Palladium-Catalyzed Annulation of 4-Quinolones with 2-Bromobenzyl Bromides

Abstract

A straightforward approach toward the assembly of phenanthridinone heterocycles has been developed through the palladium-catalyzed N-benzylation/intramolecular coupling reactions of readily prepared 4-quinolones with commercially available 2-bromobenzyl bromide derivatives. The target products were prepared in moderate to good yields, with tolerance of various functional groups.

Key words

one-pot reaction - palladium catalysis - quinolones - phenanthridinones - polycyclic heterocycles - bromobenzyl bromides

• References and Notes

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• 18 Phenanthridinone Derivatives 7 and 9; General Procedure A mixture of the appropriate quinolone 1 (1 mmol), 2-bromobenzyl bromide 5 or 8 (1.5 mmol), and K₂CO₃ (2 mmol) in anhyd DMF (3 mL) was stirred at 80 °C for 2 h, then cooled to r.t. TBAB (1.5 equiv), K₂CO₃ (1.5 equiv), and Pd(OAc)₂ (10 mol %) were added to the reaction vessel under argon, and the mixture was heated at 80 °C for 3 h. When the reaction was complete, the mixture was cooled and diluted with H₂O then extracted with EtOAc. The combined organic extracts were washed with H₂O and brine, dried (Na₂SO₄), filtered, and concentrated. The residue was purified by column chromatography [silica gel, CHCl₃–MeOH (9:1)]. Ethyl 2-Fluoro-4-oxo-4H,8H-pyrido[3,2,1-de]phenanthridine-5-carboxylate (7b) Light-yellow solid; yield: 0.116 g (85%); mp 230–232 °C. IR (KBr): 3423, 2924, 1721, 1603 cm^–1. ¹H NMR (400 MHz, DMSO-d₆ ): δ = 8.67 (s, 1 H, ArH), 8.34 (dd, J = 3.2, 6.4 Hz, 1 H, ArH), 8.15–8.13 (m, 1 H, ArH), 7.78 (dd, J = 3.2, 5.6 Hz, 1 H, ArH), 7.49–7.46 (m, 2 H, ArH), 7.36 (t, J = 4.8 Hz, 1 H, ArH), 5.56 (s, 2 H, N–CH₂), 4.26 (q, J = 6.8 Hz, 2 H, CH₂), 1.30 (t, J = 6.4 Hz, 3 H, CH₃). ¹³C APT (100 MHz, DMSO-d₆ ): δ = 172.8, 165.2, 161.1, 158.7, 150.9, 136.3, 134.8, 133.6, 130.5, 130.3, 128.8, 128.2, 122.1, 121.7, 121.4, 120.9, 120.8, 111.6, 111.4, 110.4, 60.2, 56.8, 14.7. HRMS (TOF-ES+): m/z [M + H]⁺ calcd for C₁₉H₁₅FNO₃: 324.1 found: 324.0253.
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