Synthesis of Phenanthridinones by Palladium-Catalyzed Cyclization of N-Aryl-2-aminopyridines with 2-Iodobenzoic Acids in Water

Abstract

The first Pd-catalyzed cyclization of N-aryl-2-aminopyridines with 2-iodobenzoic acids for the synthesis of phenanthridinones through C–H bond activation under very low catalyst loadings (down to 0.1 mol% Pd) in water is reported. This protocol features a broad substrate scope and provides easy efficient access to various phenanthridinones.

Key words

phenanthridinones - palladium catalysis - cyclization - arylaminopyridines - iodobenzoic acids

• References and Notes

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• 16 Phenanthridinones 3; General Procedure Pd(OAc)₂ (4.5 mg, 0.02 mmol) was dissolved in CH₂Cl₂ (1 mL) and 10 μL of the solution was added to a Schlenk tube equipped with a Teflon-coated magnetic stirrer bar. The solvent was then evaporated under high vacuum. The appropriate N-aryl-2-aminopyridine 1 (0.20 mmol), 2-iodobenzoic acid 2 (0.26 mmol), and Ag₂O (32 mg, 0.14 mmol) were added to the Schlenk tube. Water (1.0 mL) was added, the tube was placed in a preheated oil bath (120 °C), and the mixture was stirred for 3 h. When the reaction was complete, the reaction tube was allowed to cool to r.t. and EtOAc was added. The organic layer was separated, and the aqueous layer was washed with EtOAc. The filtrate was concentrated under reduced pressure, and the crude product was purified by flash column chromatography (silica gel). 5-Pyridin-2-ylphenanthridin-6(5H)-one (3a) White solid; yield: 50 mg (93%); mp 185–186 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.77 (d, J = 4.1 Hz, 1 H), 8.53 (d, J = 7.9 Hz, 1 H), 8.27–8.22 (m, 2 H), 7.97–7.93 (m, 1 H), 7.76–7.73 (m, 1 H), 7.57–7.53 (m, 1 H), 7.46–7.42 (m, 2 H), 7.28–7.21 (m, 2 H), 6.51 (d, J = 8.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 161.7, 151.9, 150.6, 139.3, 138.2, 134.2, 133.0, 129.1, 128.8, 128.1, 125.7, 124.8, 124.1, 123.1, 122.9, 121.9, 118.9, 116.4. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₈H₁₃N₂O: 273.1028; found: 273.1036.
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