β-Nitroacrylates as Precursors of Tetrasubstituted Furans in a One-Pot Process and under Acidic Solvent-Free Conditions

Abstract

The reaction of α-functionalized carbonyl derivatives with β-nitroacrylates, catalyzed by acidic alumina and in the absence of solvent, allows the one-pot synthesis of tetrasubstituted furan derivatives, in which at least two powerful functionalities are present in the 3- and 4-positions.

Key words

heterocycles - heterogeneous catalysis - furans - β-nitro-acrylates - domino reaction

References and Notes

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13

Typical Procedure for the Synthesis of Compounds 3
To a stirred mixture of the active methylene derivative 1 (1 mmol) and β-nitroacrylate 2 (1 mmol), acidic alumina (1.2 g) was added. The resulting heterogeneous mixture was initially stirred at r.t., then heated at 60 ˚C, and stirred for the appropriate time (see Table  [²] ; reaction progress was monitored by TLC). After completion of the reaction the cooled heterogeneous system was directly charged onto a silica gel column (eluting with hexanes-EtOAc) to give the pure product 3.
Spectroscopic Data for Representative Compounds.
Compound 3aa: clear oil. IR (neat): ν = 1050, 1189, 1301, 1577, 1684, 1716 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.21 (t, 3 H, J = 7.7 Hz), 1.32 (t, 3 H, J = 7.3 Hz), 2.35 (s, 3 H), 2.40 (s, 3 H), 2.86 (q, 2 H, J = 7.7 Hz), 4.29 (q, 2 H, J = 7.3 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 12.6, 13.2, 14.4, 21.2, 31.2, 60.9, 112.1, 123.0, 153.7, 161.8, 163.8, 197.3. MS (EI, 70 eV): m/z = 224 [M⁺], 181, 178 (100), 163, 135, 122, 108, 57, 43, 29. Anal. Calcd for C₁₂H₁₆O₄ (224.25): C, 64.27; H, 7.19. Found: C, 64.34; H, 7.23.
Compound 3ba: clear oil. IR (neat): ν = 1097, 1210, 1589, 1719 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.21 (t, 3 H, J = 7.7 Hz), 1.31 (t, 6 H, J = 7.3 Hz), 2.43 (s, 3 H), 2.80 (q, 2 H, J = 7.7 Hz), 4.27 (q, 4 H, J = 7.3 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 12.6, 13.3, 14.3, 14.4, 20.8, 60.7, 60.8, 113.1, 113.8, 155.7, 160.2, 163.9. MS (EI, 70eV): m/z = 254 [M⁺], 208 (100), 180, 152, 108, 43. Anal. Calcd for C₁₃H₁₈O₄ (254.28): C, 61.40; H, 7.14. Found: C, 61.51; H, 7.19.
Compound 3de: clear oil. IR (neat): ν = 1046, 1190, 1582, 1687, 1735 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.36 (t, 3 H, J = 7.3 Hz), 2.08-2.17 (m, 2 H), 2.46-2.51 (m, 2 H), 2.48 (s, 3 H), 2.82 (t, 2 H, J = 6.4 Hz), 4.32 (q, 2 H, J = 7.3 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 13.5, 14.4, 22.4, 23.6, 38.8, 60.9, 111.9, 119.6, 158.5, 163.6, 165.8, 192.2. MS (EI, 70 eV): m/z = 222 [M⁺], 194, 176 (100), 166, 138, 78, 43. Anal. Calcd for C₁₂H₁₄O₄ (222.24): C, 64.85; H, 6.35. Found: C, 64.94; H, 6.41.
Compound 3gh: clear oil. IR (neat): ν = 1223, 1583, 1689, 1736 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.11 (s, 6 H), 1.35 (t, 3 H, J = 7.3 Hz), 1.60-1.74 (m, 4 H), 2.32 (t, 2 H, J = 6.8 Hz), 2.38 (s, 2 H), 2.69 (s, 2 H), 2.89 (t, 2 H, J = 6.8 Hz), 3.64 (s, 3 H), 4.31 (q, 2 H, J = 7.3 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.3, 24.5, 27.1, 27.6, 28.6, 33.8, 35.1, 37.5, 53.3, 61.0, 111.7, 118.4, 162.1, 163.5, 165.0, 174.0, 191.9. MS (EI, 70eV): m/z = 350 [M⁺], 319, 304, 272, 244, 231, 217 (100), 55, 29. Anal. Calcd for C₁₉H₂₆O₆ (350.41): C, 65.13; H, 7.48. Found: C, 65.22; H, 7.56.
Compound 3hc: clear oil. IR (neat): ν = 691, 1112, 1492, 1586, 1603, 1721, 2232, 3062 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 0.90 (t, 3 H, J = 6.8 Hz), 1.31-1.39 (m, 4 H), 1.41 (t, 3 H, J = 7.3 Hz), 1.68-1.79 (m, 2 H), 3.05 (t, 2 H, J = 7.7 Hz), 4.38 (q, 2 H, J = 7.3 Hz), 7.40-7.50 (m, 3 H), 7.98 (d, 2 H, J = 7.3 Hz). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.1, 14.2, 22.4, 27.6, 27.7, 31.4, 61.3, 92.1, 114.2, 114.5, 125.7, 127.7, 129.2, 130.5, 158.7, 161.8, 163.3. MS (EI, 70eV): m/z = 311 [M⁺], 282, 254, 226 (100), 105, 77, 29. Anal. Calcd for C₁₉H₂₁NO₃ (311.37): C, 73.29; H, 6.80; N, 4.50. Found: C, 73.33; H, 6.85; N, 4.46.