Palladium-Catalyzed Cross-Coupling of 1,3,4-Oxadiazoles and Styrenes: An Efficient Method to Synthesize 2-Alkenyl-1,3,4- Oxadiazoles^§

^§ Part 240 in the Series ‘Studies on Novel Synthetic Methodologies’

Abstract

2-Alkenyl-1,3,4-oxadiazole derivatives have been prepared by cross-coupling of 1,3,4-oxadiazoles with styrenes by using palladium(II) trifluoroacetate [Pd(TFA)₂] as a catalyst, 1,10-phenanthroline as a ligand, silver trifluoroacetate as an oxidant, and toluene as a solvent. The products were formed in high yields and no byproducts were detected.

Keywords

oxadiazoles - styrenes - palladium catalysis - cross-coupling - silver trifluoroacetate - alkenylation

• References and Notes

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• 16a 2-Alkenyl- 1,3,4-oxadiazoles 3a–q; General Procedure A 10 mL round-bottomed flask was charged with the appropriate 1,3,4-oxadiazole 1 (0.5 mmol), styrene 2 (1.5 mmol), Pd(TFA)₂ (10 mol%), 1,10-phen (10 mol%), AgTFA (2.0 equiv), and toluene (3 mL), and the mixture was stirred at 120 °C under N₂ for 24 h until the starting materials were consumed (TLC). The mixture was then allowed to cool and extracted with EtOAc (2 × 10 mL). The organic extracts were combined, dried ­(Na₂SO₄), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (silica gel, 60 × 120 mesh, EtOAc-hexane 10:90). 2-(4-Methoxyphenyl)-5-[(E)-styryl]-1,3,4-oxadiazole (3a)^15b White solid; yield: 113 mg (82%); mp 135–137 °C; IR (KBr): 2382, 1609, 1493, 1449, 1257 cm^–1. ¹H NMR (200 MHz, CDCl₃): δ = 8.07 (d, J = 8.0 Hz, 2 H), 7.65–7.52 (m, 3 H), 7.48–7.31 (m, 4 H), 7.02 (d, J = 14.0 Hz, 2 H), 3.90 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 162.9, 138.8, 135.1, 130.0, 129.1, 128.9, 127.8, 116.3, 114.8, 110.2, 55.7. ESIMS: m/z 279 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₅N₂O₂: 279.1133; found: 279.1136. 2-[(E)-Styryl]-5-(4-tolyl)-1,3,4-oxadiazole (3c)^15b White solid; yield: 110 mg (85%); mp 127–129 °C; IR (KBr): 2378, 1642, 1492, 1443, 1258 cm^–1. ¹H NMR (200 MHz, CDCl₃): δ = 7.99 (d, J = 8.0 Hz, 2 H), 7.60–7.52 (m, 3 H), 7.41–7.28 (m, 5 H), 7.05 (d, J = 14.0 Hz, 1 H), 2.42 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 164.1, 142.3, 138.8, 134.9, 130.1, 130.0, 129.2, 127.6, 126.9, 121.1, 110.0, 21.2. ESIMS: m/z = 263 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₅N₂O: 263.1184; found: 263.1185. 2-[(E)-Styryl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole (3e)^15b White solid; yield: 128 mg (82%); mp 146–148 °C; IR (KBr): 2382, 1643, 1518, 1329, 1163 cm^–1. ¹H NMR (200 MHz, CDCl₃): δ = 8.26 (d, J = 8.0 Hz, 2 H), 7.79 (d, J = 8.0 Hz, 2 H), 7.64–7.52 (m, 3 H), 7.46–7.38 (m, 3 H), 7.09 (d, J = 14.0 Hz, 1 H). ¹³C NMR (50 MHz, CDCl₃): δ = 162.9, 139.9, 134.4, 130.1, 129.2, 127.5, 127.2, 126.1, 109.2. ESIMS: m/z 317 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₂F₃N₂O: 317.0901; found: 317.0904. 2-[(E)-2-Biphenyl-4-ylvinyl]-5-(4-tolyl)-1,3,4-oxadiazole (3g)^15b White solid; yield: 135 mg (80%); mp 150–152 °C; IR (KBr): 2394, 1638, 1490, 1410, 1268 cm^–1. ¹H NMR (200 MHz, CDCl₃): δ = 8.01 (d, J = 8.0 Hz, 2 H), 7.68–7.57 (m, 7 H), 7.49–7.30 (m, 5 H), 7.10 (d, J = 14.0 Hz, 1 H), 2.43 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 164.5, 142.8, 142.5, 140.2, 138.4, 133.9, 129.9, 129.1, 128.0, 127.9, 127.8, 127.0, 121.1, 110.0, 21.8. ESIMS: m/z 339 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₉N₂O: 339.1497; found: 339.1511. (E)-2-[2-(Biphenyl-4-yl)vinyl]-5-(4-methoxyphenyl)-1,3,4-oxadiazole (3h)^15b White solid; yield: 155 mg (88%); mp 164–166 °C; IR (KBr): 2394, 1610, 1494, 1451, 1256 cm^–1. ¹H NMR (200 MHz, CDCl₃): δ = 8.05 (d, J = 8.0 Hz, 2 H), 7.72–7.54 (m, 7 H), 7.49–7.30 (m, 4 H), 7.10 (d, J = 14.0 Hz, 1 H), 7.01 (d, J = 8.0 Hz, 1 H), 3.91 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 162.7, 142.9, 140.0, 137.9, 134.1, 128.9, 128.8, 128.0, 127.9, 127.7, 127.1, 116.6, 114.5, 109.9, 55.2. ESIMS: m/z 355 [M + H]⁺; HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₉N₂O₂: 355.1446; found: 355.1460.