Metal-Free Phosphorylations of 1,3,4-Oxadiazoles and Related Heterocycles

Abstract

1,3,4-Oxadiazoles have been phosphorylated at C5 in yields of >90% under mild metal-free reactions conditions using triethylamine as base. Other azoles undergo analogous phosphorylations albeit in lower yields.

Key words

1,3-azole - base-promoted - metal-free substitution - 1,3,4-oxadiazole - phosphorylation

• References and Notes

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• 12 General Procedure for the Phosphorylation of Azoles – Examplified by the Synthesis of 2-Phenyl-1,3,4-oxadiazolyldiphenylphosphine (3a)¹¹ In a Schlenk tube filled with argon 2-phenyl-1,3,4-oxadiazole (1a, 1 mmol), Et₃N (277 μL, 2 mmol), ClPPh₂ (2, 180 μL, 2 mmol), and CH₂Cl₂ (1.5 mL) were added. The mixture was stirred at 40 °C for 48 h. After full conversion of 1a (as confirmed by TLC), the mixture was filtered through a pad of silica gel, concentrated and purified by silica gel column chromatography providing 3a in 90% yield. White solid, mp 85.2–86.0 °C. ¹H NMR (300 MHz, CDCl₃): δ = 7.96–8.00 (m, 2 H), 7.62–7.55 (m, 4 H), 7.47–7.43 (m, 2 H), 7.42–7.36 (m, 7 H). ¹³C NMR (75 MHz, CDCl₃): δ = 167.8 (¹ J _C–P = 32.6 Hz), 167.0, 134.0 (² J _C–P = 21.1 Hz), 132.0 (¹ J _C–P = 6.3 Hz), 131.9, 130.2, 129.0 (³ J _C–P = 2.3 Hz), 128.9, 127.2, 123.7. ³¹P NMR (122.0 MHz, CDCl₃): δ = –25.0 ppm. MS (EI): m/z = 330 [M⁺]. HRMS: m/z [M⁺] calcd for C₂₀H₁₅ON₂NaP: 353.0814; found: 353.0813