Palladium-Catalyzed Dehydrogenation Coupling–Cyclization Reactions of Acetylenic Acids with Iodonium Ylides for the Synthesis of 2(5H)-Furanones

Abstract

A new route for the synthesis of 2(5H)-furanones is presented via Pd(PPh₃)₄-catalyzed cascade reaction of acetlenic acids with iodonium ylides using K₂CO₃ as the base. The cascade proceeds through dehydrogenation coupling and cyclization under mild conditions.

Key words

palladium - dehydrogenation - acetylenic acids - iodonium ylides - 2(5H)-furanones

• References and Notes

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• 11 Typical Experimental Procedure for the Palladium-Catalyzed Dehydrogenation Coupling–Cyclization Reactions of Acetylenic Acids with Iodonium Ylides To a Schlenk tube were added 3-phenylpropiolic acid (1a, 29.2 mg, 0.2 mmol), dimethyl 2-(phenyl-λ³-iodanylidene)malonate (2a, 80.2 mg, 0.24 mmol), Pd(PPh₃)₄ (13.8 mg, 0.06 mmol), K₂CO₃ (60.8 mg, 0.4 mmol), and CH₂Cl₂ (2 mL). Then the tube was charged with argon and was stirred at r.t. for the indicated time until complete consumption of starting material as monitored by TLC and GC–MS analysis. After the reaction was finished, the reaction diluted in Et₂O and concentrated in vacuum, and the resulting residue was purified by silica gel column chromatography (hexane–EtOAc) to afford the desired product 3aa (54.1 mg, 98%). Dimethyl 5-Oxo-3-phenylfuran-2,2(5H)-dicarboxylate (3aa) Yield: 54.1 mg (98%); white solid; mp 104–106 °C. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.56 (d, J = 8.0 Hz, 2 H), 7.42–7.37 (m, 3 H), 6.46 (s, 1 H), 3.76 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 170.13, 164.61, 162.24, 131.86, 128.86, 128.54, 116.20, 99.99, 88.06, 54.05. IR (neat): 2958, 2852, 1779, 1749, 1262, 797cm^–1. LRMS (EI, 70 eV): m/z (%) = 276 (5) [M], 232 (9), 188 (77), 161 (100), 115 (32), 102 (60). ESI-HRMS: m/z calcd for C₁₀H₁₃O₆ [M + H]⁺: 227.0712; found: 277.0708. Dimethyl 3-(4-Methoxyphenyl)-5-oxofuran-2,2(5H)-dicarboxylate (3ba) Yield: 53.8 mg (88%); colorless oil. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.56 (d, J = 8.0 Hz, 2 H), 6.88 (d, J = 8.0 Hz, 2 H), 6.33 (s, 1 H), 3.86 (s, 6 H), 3.84 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 164.89, 162.80, 130.98, 120.91, 114.28, 113.19, 60.42, 55.50, 54.00, 53.87. IR (neat): 2924, 2855, 1761, 1376, 1265, 743 cm^–1. LRMS (EI, 70 eV): m/z (%): 307 (1) [M], 247 (10), 219 (27), 189 (3), 175 (3), 132 (37), 117 (15), 59 (100). ESI-HRMS: m/z calcd for C₁₀H₁₃O₆ [M + H]⁺: 307.0818; found: 307.0812. Dimethyl 3-Ethyl-5-oxofuran-2,2(5H)-dicarboxylate (3ca) Yield: 33.8 mg (74%); colorless oil. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.92 (s, 1 H), 3.82 (d, J = 12.0 Hz, 6 H), 2.56–2.50 (m, 2 H), 1.19 (d, J = 8.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 170.36, 169.22, 164.31, 117.00, 88.7, 60.41, 53.90, 21.59, 11.20. IR (neat): 2954, 2924, 2854, 2361, 1784, 1755, 1458, 742, 684 cm^–1. LRMS (EI, 70 eV): m/z (%) = 226 (9) [M], 184 (20) [M], 168 (16), 141 (100), 126 (17). ESI-HRMS: m/z calcd for C₁₀H₁₃O₆ [M + H]⁺: 229.0712; found: 229.0707. Ethyl 5-Oxo-3-phenyl-2,5-dihydrofuran-2-carboxylate (3ab) Yield: 37.2 mg (80%); white solid; mp 93–95 °C. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.54 (t, J = 4.0 Hz, 2 H), 7.42–7.39 (m, 3 H), 6.37 (s, 1 H), 5.81 (s, 1 H), 4.11 (m, 2 H), 1.11 (m, 6 H). ¹³CNMR (100 MHz, CDCl₃, 25 °C): δ = 172.18, 166.16, 162.43, 132.02, 129.18, 128.71, 127.49, 114.50, 80.06, 62.71, 13.83. IR (neat): 3108, 2919, 2850, 1763, 1465, 1155, 763 cm^–1. LRMS (EI, 70 eV): m/z (%) = 233 (3) [M], 203 (25), 146 (100), 131 (29). ESI-HRMS: m/z calcd for C₁₃H₁₃O₄ [M + H]⁺: 233.0814; found: 233.0808. Methyl 5-Oxo-3-phenyl-2,5-dihydrofuran-2-carboxylate (3ac) Yield: 36.2 mg (83%); white solid; mp 75–76 °C. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.54 (t, J = 4.0 Hz, 2 H), 7.44–7.40 (m, 3 H), 6.38 (s, 1 H), 5.85 (s, 1 H), 3.65 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 172.15, 166.71, 162.32, 132.09, 129.29, 128.85, 128.82, 128.60, 171.44, 114.45, 53.38. IR (neat): 2957, 1766, 1621, 1437, 1158, 788, 688 cm^–1. LRMS (EI, 70 eV): m/z (%) = 218 (10) [M], 159 (100), 146 (20), 77 (56). ESI-HRMS: m/z calcd for C₁₂H₁₀O₄ [M + H]⁺: 219.0657; found: 219.0650. Ethyl 2-Benzoyl-5-oxo-3-phenyl-2,5-dihydrofuran-2-carboxylate (3ad) Yield: 64.5 mg (96%); light yellow solid; mp 48–50 °C. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.96 (d, J = 8.0 Hz, 2 H), 7.60 (d, J = 8.0 Hz, 3 H), 7.43–7.36 (m, 5 H), 6.50 (s, 1 H), 4.16–4.10 (m, 2 H), 1.02 (t, J = 6.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 189.13, 170.15, 165.88, 164.38, 134.15, 134.02, 131.64, 129.63, 129.29, 129.23, 128.73, 128.67, 116.49, 63.49, 13.67. IR (neat): 2925, 2854, 1767, 1712, 1450, 1262, 1028, 712 cm^–1. LRMS (EI, 70 eV): m/z (%) = 337 (1) [M], 207 (1), 105 (100), 103 (2), 77 (28). ESI-HRMS: m/z calcd for C₂₀H₁₇O₅ [M + H]⁺: 337.1076; found: 337.1071. Vinyl 2-Acetyl-5-oxo-3-phenyl-2,5-dihydrofuran-2-carboxylate (3ae) Yield: 44.6 mg (82%); pale yellow oil. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.47–7.45 (m, 2 H), 7.42–7.37 (m, 3 H), 6.49 (s, 1 H), 5.42–5.35 (m, 1 H), 5.00–4.90 (m, 2 H), 2.12 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 203.09, 117.82, 164.87, 131.71, 129.35, 129.06, 127.64, 121.02, 116.56, 93.90, 37.11, 29.71, 24.06. IR (neat): 2923, 2852, 1766, 1188, 769 cm^–1. LRMS (EI, 70 eV): m/z (%) = 272 (6) [M], 245 (14), 201 (37), 158 (100), 77 (30). ESI-HRMS: m/z calcd for C₁₅H₁₃O₅ [M + H]⁺: 273.0763; found: 273.0758. Methyl 5-Oxo-3-phenyl-2-propionyl-2,5-dihydrofuran-2-carboxylate (3af) Yield: 48.2 mg (88%); white solid; mp 101–103. ¹H NMR (400 MHz,CDCl₃, 25 °C): δ = 7.61–7.59 (d, J = 8.0 Hz, 2 H), 7.49–7.27 (m, 3 H), 6.54 (s, 1 H), 3.83 (s, 3 H), 2.87–2.77 (m, 1 H), 2.65–2.55 (m, 1 H), 1.09–1.05 (t, J = 8.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 201.0, 170.4, 165.4, 162.8, 131.9, 120.3, 128.8, 128.8, 128.7, 127.4, 115.7, 92.5, 92.5, 79.0 , 77.4, 53.9, 31.4. IR (neat): 2957, 2851, 2359, 1776, 1255, 739 cm^–1. LRMS (EI, 70 eV): m/z (%) = 274 (6) [M], 259 (14), 200 (37), 146 (100), 77 (30). ESI-HRMS: m/z calcd for C₁₅H₁₄O₅ [M + H]⁺: 274.0841; found: 275.0837. Methyl 2-Butyryl-5-oxo-3-phenyl-2,5-dihydrofuran-2-carboxylate (3ag) Yield: 44.9 mg (78%); white solid; mp 113–117. ¹H NMR (400 MHz,CDCl₃, 25 °C): δ = 7.61–7.59 (d, J = 8.0 Hz, 2 H), 7.49–7.41 (m, 3 H), 6.54 (s, 1 H), 3.83 (s, 3 H), 2.77–2.71 (m, 1 H), 2.58–2.40 (m, 1 H), 1.66–1.55 (m, 2 H), 0.89–0.86 (t, J = 4.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 198.0, 170.4, 165.6, 164.2, 162.8, 162.6, 131.8, 129.1, 128.9, 128.7, 127.5, 115.9, 114.5, 92.7, 80.2, 71.8, 26.0, 21.5, 21.3. IR (neat): 2937, 2811, 2359, 1789, 1345, 741 cm^–1. LRMS (EI, 70 eV): m/z (%) = 288 (1) [M], 240 (12), 210 (13) 160 (6), 77 (100). ESI-HRMS: m/z calcd for C₁₆H₁₆O₅ [M + H]⁺: 288.0997; found: 288.0992. Methyl 2-Isobutyryl-5-oxo-3-phenyl-2,5-dihydrofuran-2-carboxylate (3ah) Yield: 44.9 mg (78%); white solid; mp 110.3–112.0 ¹H NMR (400 MHz,CDCl₃, 25 °C): δ = 7.60–7.40 (m, 2 H), 7.45–7.41 (m, 3 H), 6.55 (s, 1 H), 3.84 (s, 3 H), 3.09 (t, J = 6.0 Hz, 1 H), 1.23–1.21 (d, J = 8.0 Hz, 3 H), 1.01–0.99 (d, J = 8.0 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃, 25 °C): δ = 204.68, 170.51, 165.49, 162.99, 131.86, 128.90, 128.71, 115.96, 92.92, 53.89, 36.56, 19.21, 19.17. IR (neat): 2957, 2851, 2359, 1776, 1255, 739 cm^–1. LRMS (EI, 70 eV): m/z (%) = 274 (6) [M], 259 (14), 200 (37) 146 (100), 77 (30). ESI-HRMS: m/z calcd for C₁₆H₁₆O₅ [M + H]⁺: 288.2951; found: 288.2946. 4-Acetyl-4-benzoyl-3-phenylcyclopent-2-enone (3ai) Yield 47.4 mg (75%); yellow solid; mp 52–55 °C. ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.89 (d, J = 8.0 Hz, 2 H), 7.62 (t, J = 10.0 Hz, 3 H),7.49–7.43 (m, 5 H), 6.67 (s, 1 H), 2.39 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 170.51, 164.29, 134.08, 132.01, 129.70, 129.26, 128.87, 115.84, 24.78. IR (neat): 2925, 2854, 1770, 1693, 1450, 1266, 713, 685 cm^–1. LRMS (EI, 70 eV): m/z (%) = 306 (0.02) [M], 218 (4), 189 (6), 173 (27), 158 (65), 105 (100). ESI-HRMS: m/z calcd for C₂₀H₁₇O₃ [M + H]⁺: 306.3121; found: 306.0892
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