One-Pot Synthesis of E-Alkylidene Derivatives of 3H-Furan-2-ones from 4-Pentynoic Acid and Aldehyde

Abstract

4-Pentynoic acid reacts with aldehyde under the co-catalyst system of Wilkinson’s complex and 2-aminopyridine to give E-alkylidene derivatives of 3H-furan-2-one through the transition metal-catalyzed cyclization of 4-pentynoic acid followed by condensation of the resulting lactone with aldehyde.

lactone - lactam - Wilkinson’s complex - aldehyde - 4-pentynoic acid

References

1a Rossi R. Bellina F. Mannina L. Tetrahedron  1997,  53:  1025 

1b Bellina F. Carpita A. De Santis M. Rossi R. Tetrahedron  1994,  50:  12029 

2 Rossi R. Bellina F. Bechini C. Mannina L. Vergamini P. Tetrahedron  1998,  54:  135 

3 Huang Y. Alper H. J. Org. Chem.  1991,  56:  4534 

4a Rao YS. Chem. Rev.  1976,  76:  625 

4b Rao YS. Chem. Rev.  1964,  64:  353 

For intermolecular hydroacylation using various aldehydes or aldimines with alkenes see:

5a Jun C.-H. Lee D.-Y. Lee H. Hong J.-B. Angew. Chem. Int. Ed.  2000,  39:  3070 

5b Jun C.-H. Hong J.-B. Org. Lett.  1999,  1:  887 

5c Jun C.-H. Lee D.-Y. Hong J.-B. Tetrahedron Lett.  1997,  38:  6673 

5d Jun C.-H. Huh C.-W. Na S.-J. Angew. Chem. Int. Ed.  1998,  37:  145 

5e Jun C.-H. Lee H. Hong J.-B. J. Org. Chem.  1997,  62:  1200 

6 For intermolecular hydroacylation using various aldehydes with alkynes see: Jun C.-H. Lee H. Hong J.-B. Kwon B.-I. Angew. Chem. Int. Ed.  2002,  41:  2146 

7

The E-stereochemistry of compounds 5a, 5c, and 5d was determined by NOESY spectroscopic analysis.

8

The reaction of 4-pentynoic acid (2) and (PPh₃)₃RhCl (3, 5 mol%) was performed in benzene-d ₆ at 100 °C for 3 h to afford a 100% yield of 5-methylenedihydrofuran-2-one (6); the structure was confirmed by ¹H NMR spectroscopy. ¹H NMR (benzene-d ₆): δ = 4.60-4.58 (m, 1 H), 4.03-4.01 (m, 1 H), 2.29-2.20 (m, 2 H), 2.12-2.03 (m, 2 H).

9a Marder TB. Chan DM.-T. Fultz WC. Calabrese JC. Milstein D. J. Chem. Soc., Chem. Commun.  1987,  1885 

9b Chan DM.-T. Marder TB. Milstein D. Taylor NJ. J. Am. Chem. Soc.  1987,  109:  6385 

10a Jun C.-H. Hwang D.-C. Na S.-J. Chem. Commun.  1998,  1405 

10b Reger DL. Garza DG. Baxter JC. Organometallics  1990,  9:  873 

11 Egorova AY. Reshetov PV. Morozova NA. Sedavkina VA. In Chemistry of Heterocyclic Compounds   Plenum Pub. Co.; New York: 1997.  p.910 

12 Moneer AI. Salem A. Mohamed el-kasaby A. J. Chem. Soc. Pak.  1987,  9:  245 

13

General Procedure for One-Pot Synthesis of (E)-Alkylidene Derivatives of 3H-Furan-2-ones from 4-Pentynoic Acid and Aldehyde
A screw-capped pressure vial (1 mL) was charged with benzaldehyde (1a, 22.9 mg, 0.216 mmol), 4-pentynoic acid (2, 42.3 mg, 0.432 mmol), (PPh₃)₃RhCl (3, 10 mg, 0.011 mmol), 2-aminopyridine (4c, 8.1 mg, 0.086 mmol), and toluene (0.2 mL). The reaction mixture was stirred at 100 °C for 12 h. After the reaction reached completion, the mixture was purified by column chromatography (n-hexane-ethyl acetate, 5:1) to give 5a (33.3 mg, 83%).
Compound 5a: IR (KBr): 3058, 2982, 2931, 1770, 1734, 1668, 1602, 1424, 1266, 899, 746 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.19 (s, 3 H), 6.29 (s, 1 H), 7.28 (s, 1 H), 7.46-7.34 (m, 3 H), 7.56-7.53 (m, 2 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.0, 102.1, 125.5, 128.5, 129.1, 130.1, 134.0, 135.2, 158.4, 170.0. MS (EI, 70 eV): m/z (%) = 43 (100), 63 (9), 89 (9), 115 (54), 158 (21), 186 (84) [M + H⁺]. HRMS: m/z calcd for C₁₂H₁₀O₂ [M + H]⁺: 186.0681; found: 186.0683.
Compound 5b: IR (KBr): 3058, 2987, 2839, 1770, 1638, 1601, 1510, 1428, 1266, 899, 746 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.18 (s, 3 H), 3.85 (s, 3 H), 6.26 (s, 1 H), 6.94 (d, J = 8.4 Hz, 2 H), 7.23 (s, 1 H), 7.51 (d, J = 8.4 Hz, 2 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 14.9, 55.6, 102.0, 114.7, 123.1, 128.0, 131.9, 134.0, 157.3, 161.2, 170.0. MS (EI, 70 eV): m/z (%) = 43 (11), 102 (11), 115 (3.6), 145 (100), 173 (4.3), 188 (17.3), 216 (62.6) [M + H⁺]. HRMS: m/z calcd for C₁₃H₁₂O₃ [M + H]⁺: 216.0786, found: 216.0782. Anal. Calcd for C₁₃H₁₂O₃: C, 72.21; H, 5.59. Found: C, 72.36; H, 5.48.
Compound 5c: IR (KBr): 3053, 2986, 1770, 1632, 1509, 1418, 1263, 895, 737 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.20 (s, 3 H), 6.24 (s, 1 H), 7.16-7.04 (m, 2 H), 7.23 (s, 1 H), 7.56-7.51 (m, 2 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.0, 101.8, 116.3, 116.6, 125.3, 131.6, 131.9, 132.1, 132.7, 161.6, 165.6, 170.0. MS (EI, 70 eV): m/z (%) = 43 (60), 83 (5), 107 (6), 133 (48), 176 (21), 204 (100) [M + H⁺]. Anal. Calcd for C₁₂H₉FO₂: C, 70.58; H, 4.44; found: C, 70.44; H, 4.51.
Compound 5d: IR (KBr): 3053, 2990, 1778, 1638, 1601, 1510, 1426, 1327, 899, 746 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.23 (s, 3 H), 6.27 (m, 1 H), 7.28 (s, 1 H), 7.70-7.58 (m, 4 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.2, 102.0, 126.0, 126.1, 126.2, 127.8, 130.0, 131.7, 138.7, 160.2, 169.4. MS (EI, 70 eV): m/z (%) = 43 (85), 133 (8), 164 (7), 183 (10), 235 (6), 254 (100) [M + H⁺]. HRMS: m/z calcd for C₁₃H₉O₂F₃ [M + H]⁺: 254.0555; found: 254.0557. Anal. Calcd for C₁₃H₉F₃O₂: C, 61.42; H, 3.57. Found: C, 61.34; H, 3.47.
Compound 5e: IR (KBr): 3058, 2987, 1765, 1638, 1424, 1266, 894, 746 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.19 (s, 3 H), 6.19 (s, 1 H), 7.27 (s, 1 H), 7.41-7.31 (m, 2 H), 7.59 (d, J = 1.6 Hz, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 14.9, 102.2, 124.1, 127.2, 127.4, 127.4, 129.7, 137.3, 157.5, 170.3. MS (EI, 70 eV): m/z (%) = 18 (8), 43 (41), 77 (8), 96 (4), 121 (78), 164 (21), 192 (100) [M + H⁺]. HRMS: m/z calcd for C₁₀H₈O₂S [M + H]⁺: 192.0245, found: 192.0249. Anal. Calcd for C₁₀H₈O₂S: C, 62.48; H, 4.19. Found: C, 62.51; H, 4.28.
Compound 5f: IR (KBr): 3053, 2992, 1770, 1632, 1424, 1266, 1169, 930, 741 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.23 (s, 3 H), 6.40 (s, 1 H), 7.44 (s, 1 H), 7.57-7.49 (m, 2 H), 7.65 (dd, J = 1.6, 7.0 Hz, 1 H), 7.89-7.82 (m, 3 H), 7.99 (s, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.1, 102.4, 125.6, 126.1, 127.1, 127.8, 128.0, 128.9, 129.0, 131.2, 132.9, 133.5, 134.0, 134.2, 158.5, 170.2. MS (EI, 70 eV): m/z (%) = 43 (29), 115 (7.7), 139 (5.2), 165 (100), 208 (23.6), 236 (58.2) [M + H⁺]. HRMS: m/z calcd for C₁₆H₁₂O₂ [M + H]⁺: 236.0837; found: 236.0817. Anal. Calcd for C₁₆H₁₂O₂: C, 81.34; H, 5.12. Found: C, 81.36; H, 5.13.
Compound 5g: IR (KBr): 3053, 2987, 1755, 1638, 1617, 1424, 1271, 889, 741 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.12 (s, 3 H), 4.18 (s, 5 H), 4.57-4.52 (m, 4 H), 6.02 (s, 1 H), 7.16 (s, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.0, 70.1, 70.5, 72.0, 100.2, 102.5, 121.8, 136.3, 155.0, 170.0. MS (EI, 70 eV): m/z (%) = 43 (7), 56 (14), 121 (42), 223 (55), 229 (22), 266 (52), 294 (100) [M + H⁺]. HRMS: m/z calcd for C₁₆H₁₄O₂ Fe [M + H]⁺: 294.0343; found: 294.0311. Anal. Calcd for C₁₆H₁₄ FeO₂: C, 65.33; H, 4.80. Found: C, 63.63; H, 5.00.
Compound 5h: IR (KBr): 3052, 2984, 2933, 2853, 1776, 1648, 1421, 1267, 913, 704 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.71-0.89 (m, 10 H), 2.11 (s, 3 H), 2.36-2.32 (m, 1 H), 5.83 (s, 1 H), 6.44 (d, J = 9.84 Hz, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 14.8, 25.6, 25.8, 32.2, 39.8, 101.1, 126.4, 144.8, 155.7. MS (EI, 70 eV): m/z (%) = 43 (42), 67 (10), 82 (38), 110 (100), 124 (7), 149 (5), 192 (29) [M + H⁺].
Compound 5i: IR (KBr): 2941, 2859, 1779, 1632, 1602, 1439, 1296, 909, 741 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.77-1.60 (m, 4 H), 2.13 (s, 3 H), 2.36-2.26 (m, 4 H), 6.06 (s, 1 H), 6.33 (t, J = 3.98 Hz, 1 H), 6.87 (s, 1 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 14.8, 21.6, 22.4, 26.9, 27.1, 99.8, 102.8, 122.0, 136.5, 138.4, 142.4, 155.3. MS (EI, 70 eV): m/z (%) = 43 (79), 80 (100), 91 (53), 111 (24), 119 (31), 147 (61), 190 (79) [M + H⁺]. HRMS: m/z calcd for C₁₂H₁₄O₂ [M + H]⁺: 190.0994; found: 190.0993.
Compound 9: IR (KBr): 3062, 1772, 1701, 1622, 1498, 1367, 1161, 910, 733 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 2.09 (s, 3 H), 6.19 (s, 1 H), 7.35-7.32 (m, 2 H), 7.58-7.37 (m, 7 H), 7.72-7.69 (m, 2 H). ¹³C NMR (62.9 MHz, CDCl₃): δ = 15.0, 99.6, 128.0, 128.1, 129.0, 129.3, 129.4, 130.0, 130.2, 131.1, 135.1, 136.1, 146.3, 169.5. MS (EI, 70 eV): m/z (%) = 51 (6), 77 (43), 118 (67), 218 (17), 232 (34), 261 (100) [M + H⁺]. HRMS: m/z calcd for C₁₈H₁₅NO [M + H]⁺: 261.1154; found: 291.1154. Registry Number: 165263-88-7.