Synthesis of Triazole-Fused Phenanthridines through Pd-Catalyzed Intramolecular Phenyl C–H Activation of 1,5-Diaryl-1,2,3-triazoles

^§Both authors contributed equally.

Abstract

An efficient method for the synthesis of triazole-fused phenanthridines from 1,5-diaryl-1,2,3-triazoles under palladium catalysis has been developed. The reaction proceeds through Pd-catalyzed intramolecular phenyl C–H activation of 1,5-diaryl-1,2,3-triazoles. This method provides a concise and efficient pathway to construct triazolo[1,5-f]phenanthridine derivatives in excellent yields.

Key words

palladium catalyst - site-selective reactions - C–H activation - 1,5-diaryl-1,2,3-triazoles - fused phenanthridines

• References and Notes

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• 19 Synthesis of Triazolophenanthridines 2; General Procedure To a 50 mL pressure tube, 1,5-diaryl-1,2,3-triazole were added 1 (0.3 mmol), Pd(OAc)₂ (0.03 mmol), PCy₃ (0.06 mmol), CsOPiv (0.9 mmol), and toluene (2 mL) and the reaction mixture was stirred at 130 °C for 24 h. After consumption of the 1,5-disubstitued 1,2,3-triazoles monitored by TLC analysis, the mixture was treated with H₂O (15 mL) and extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with brine (3 × 5 mL), dried with Na₂SO₄, and concentrated under reduced pressure to afford a crude product. Purification by column chromatography on silica gel with EtOAc-PE (1:8) afforded the desired products 2.9-Methyl-[1,2,3]triazolo[1,5-f]phenanthridine (2a)White solid; yield: 65 mg (93%); mp 159.8–160.8 °C. IR (KBr): 3066, 2946, 2841, 1731, 1620, 1555, 1494, 1448, 1207, 1124, 1074, 1014, 826, 760, 584 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 8.64 (d, J = 8.4 Hz, 1 H), 8.39 (s, 1 H), 8.35 (d, J = 8.0 Hz, 1 H), 8.16 (s, 1 H), 8.10–8.03 (m, 1 H), 7.69–7.63 (m, 1 H), 7.61 (dd, J = 10.8, 4.1 Hz, 1 H), 7.51 (d, J = 8.3 Hz, 1 H), 2.58 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 137.3, 131.3, 130.8, 129.2, 129.0, 128.6, 127.3, 127.2, 124.8, 123.5, 123.0, 121.9, 121.9, 116.9, 21.7. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₅H₁₂N₃: 234.1026; found: 234.1031.[1,2,3]Triazolo[1,5-f]phenanthridine (2b)White solid; yield: 62 mg (95%); mp 187.2–188.4 °C. IR (KBr): 3047, 2944, 2843, 1944, 1790, 1724, 1617, 1558, 1447, 1220, 1125, 976, 822, 747, 526 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 8.75–8.73 (m, 1 H), 8.39–8.37 (m, 1 H), 8.36–8.33 (m, 1 H), 8.32–8.30 (m, 1 H), 8.04–8.01 (m, 1 H), 7.71–7.67 (m, 1 H), 7.65–7.57 (m, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 131.4, 130.8, 129.5, 129.3, 128.6, 127.3, 127.2, 127.1, 124.6, 123.5, 122.9, 121.9, 121.6, 117.0. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₄H₁₀N₃: 220.0869; found: 220.0872.11-Methyl-[1,2,3]triazolo[1,5-f]phenanthridine (2c)White solid; yield: 60 mg (86%); mp 142.1–143 °C. IR (KBr): 3045, 2948, 2849, 1957, 1786, 1710, 1623, 1564, 1512, 1449, 1393, 1226, 1126, 1079, 971, 854, 810, 756, 566 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 8.39 (dd, J = 3.0, 1.5 Hz, 1 H), 8.34 (t, J = 8.2 Hz, 1 H), 8.28 (t, J = 7.8 Hz, 1 H), 8.04 (dd, J = 9.2, 4.6 Hz, 1 H), 7.64–7.57 (m, 2 H), 7.52 (d, J = 2.7 Hz, 1 H), 7.50–7.46 (m, 1 H), 3.17 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 133.2, 132.5, 132.5, 130.7, 130.3, 129.2, 128.5, 127.9, 126.5, 125.9, 124.3, 123.3, 123.2, 121.7, 121.3, 25.2. HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₁₅H₁₂N₃: 234.1026; found: 234.1029.