Ionic Liquid Promoted Aza-Diels-Alder Reaction of Danishefsky’s Diene with Imines

Bruce Pégot; Giang Vo-Thanh

doi:10.1055/s-2005-869837

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Synlett 2005(9): 1409-1412
DOI: 10.1055/s-2005-869837

LETTER

Ionic Liquid Promoted Aza-Diels-Alder Reaction of Danishefsky’s Diene with Imines

Bruce Pégot, Giang Vo-Thanh*
Laboratoire des Réactions Sélectives sur Supports, ICMMO, CNRS UMR 8615, Université Paris-Sud, 91405 Orsay Cedex, France
Fax: 33(1)69154679; e-Mail: gvothanh@icmo.u-psud.fr;

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Publication History

Received 25 February 2005
Publication Date:
10 May 2005 (online)

Abstract
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Abstract

A highly efficient procedure for the synthesis of 2-substituted-2,3-dihydro-4-pyridone derivatives through the aza-Diels-Alder reaction under ‘green chemistry’ conditions is described. The reaction of Danishefsky’s diene with imines has been found to perform better at room temperature in ionic liquids without an acid catalyst and organic solvent: the ionic liquids are recycled while their efficiency is preserved.

Key words

ionic liquids - aza-Diels-Alder reaction - Danishefsky’s diene - imines - green chemistry

References

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15

General Procedure for the Aza-Diels-Alder Reaction of Danishefsky’s Diene with Imines A mixture of imine 2 (1 mmol), ionic liquid (0.5 equiv) and Danishefsky’s diene 1 (1.2 equiv added in two phases) was stirred at 30 °C for the period of time reported in Table [3] . The reaction mixture was extracted from the ionic liquid phase with Et₂O (3 × 10 mL). The ether layer was dried over anhydrous MgSO₄ and evaporated under reduced pressure. The residue was purified by flash column chromatography (EtOAc-pentane, 10:90→70:30) to provide 3.
The ionic liquid was dissolved in CH₂Cl₂ (20 mL) and then recycled by washing with H₂O (2 × 10 mL). The organic phase was dried over anhydrous MgSO₄, filtered and evaporated in vacuo to afford the recycled ionic liquid. Spectra data (IR, ¹H and ¹³C) were identical to the initial ionic liquid sample. This was reused without loss of efficiency (Table [3] , entry 1).
1-Benzyl-2,3-dihydro-2-phenylpyridin-4(1 H )-one (3a) IR (neat): 2926, 1635, 1591, 1494, 1453, 1382, 1205, 1078, 760, 700 cm^-1. ¹H NMR (CDCl₃): δ = 2.68 (dd, 1 H, J = 8.6 Hz, 16.6 Hz), 2.84 (dd, 1 H, J = 7.2 Hz, 16.6 Hz), 4.12 (d, 1 H, J = 15.5 Hz), 4.35 (d, 1 H, J = 15.5 Hz), 4.50 (t, 1 H, J = 7.2 Hz), 5.10 (d, 1 H, J = 7.9 Hz), 7.13 (d, 1 H, J = 7.2 Hz), 7.24-7.36 (m, 10 H). ¹³C NMR (CDCl₃): δ = 43.2, 57.1, 60.3, 98.2, 126.9, 127.5, 128.1, 129.3, 135.6, 138.2, 154.5, 190.4. HRMS (EI): m/z calcd for C₁₈H₁₇NO (M⁺), 263.1310; found, 263.1310.
1-Benzyl-2,3-dihydro-2-(4-methoxyphenyl)pyridin-4(1 H )-one (3b) IR (neat): 3050, 1634, 1574, 1514, 1383, 1254, 1030, 833, 739, 699 cm^-1. ¹H NMR (CDCl₃): δ = 2.63 (dd, 1 H, J = 8.8 Hz, 16.5 Hz), 2.76 (dd, 1 H, J = 7.0 Hz, 16.8 Hz), 3.78 (s, 3 H), 4.10 (d, 1 H, J = 15.0 Hz), 4.28 (d, 1 H, J = 15.0 Hz), 4.41 (t, 1 H, J = 8.5 Hz), 5.04 (d, 1 H, J = 7.5 Hz), 6.83 (d, 1 H, J = 8.7 Hz), 7.10-7.32 (m, 9 H). ¹³C NMR (CDCl₃): δ = 43.6, 55.3, 57.0, 60.1, 98.4, 114.3, 128.0, 128.6, 128.8, 129.3, 130.4, 135.8, 154.4, 159.5, 190.8. HRMS (EI): m/z calcd for C₁₉H₁₉NO₂ (M⁺), 293.1416; found, 293.1410.

1-Benzyl-2,3-dihydro-2-(4-chlorophenyl)pyridin-4(1 H )-one (3c) IR (neat): 3063, 1644, 1574, 1490, 1382, 1205, 1091, 825, 734, 699 cm^-1. ¹H NMR (CDCl₃): δ = 2.62 (dd, 1 H, J = 8.0 Hz, 16.8 Hz), 2.84 (dd, 1 H, J = 7.4 Hz, 16.6 Hz), 4.10 (d, 1 H, J = 15.2 Hz), 4.38 (d, 1 H, J = 15.2 Hz), 4.47 (t, 1 H, J = 7.4 Hz), 5.10 (d, 1 H, J = 8.0 Hz), 7.12 (d, 1 H, J = 8.2 Hz), 7.15-7.35 (m, 9 H). ¹³C NMR (CDCl₃): δ = 43.3, 57.3, 59.7, 98.6, 127.6, 128.3, 128.9, 135.4, 136.8, 136.9, 154.2, 190.0. HRMS (EI): m/z calcd for C₁₈H₁₆ClNO (M⁺), 297.0920; found, 297.0910.
1-Benzyl-2,3-dihydro-2-(4-nitrophenyl)pyridin-4(1 H )-one (3d) Mp 104 °C. IR (neat): 3032, 1711, 1645, 1582, 1516, 1455, 1347, 1206, 1157, 1030, 856, 734, 699 cm^-1. ¹H NMR (CDCl₃): δ = 2.60 (dd, 1 H, J = 6.8 Hz, 16.6 Hz), 2.93 (dd, 1 H, J = 7.2 Hz, 16.2 Hz), 4.12 (d, 1 H, J = 15.2 Hz), 4.44 (d, 1 H, J = 15.2 Hz), 4.61 (t, 1 H, J = 7.2 Hz), 5.13 (d, 1 H, J = 8.0 Hz), 7.12-7.45 (m, 9 H), 8.22 (d, 1 H, J = 9.0 Hz). ¹³C NMR (CDCl₃): δ = 42.8, 57.8, 59.5, 99.2, 124.2, 128.1, 128.3, 129.0, 129.6, 135.1, 145.7, 147.7, 153.9, 189.0. HRMS (EI): m/z calcd for C₁₈H₁₆N₂O₃ (M⁺), 308.1161; found, 308.1154.
1-Benzyl-2,3-dihydro-2-hexylpyridin-4(1 H )-one (3e) IR (neat): 2931, 1710, 1574, 1558, 1455, 1352, 1195, 1136, 1061, 970, 740, 699 cm^-1. ¹H NMR (CDCl₃) δ = 0.88 (t, 3 H, J = 5.7 Hz), 1.26 (m, 6 H), 1.62 (m 2 H), 1.78 (m, 2 H), 2.31 (dd, 1 H, J = 3.0 Hz, 16.5 Hz), 2.69 (dd, 1 H, J = 7 Hz, 16.5 Hz), 3.4 (m, 1 H), 4.35 (d, 1 H, J = 15.2 Hz), 4.43 (d, 1 H, J = 15.2 Hz), 4.95 (d, 1 H, J = 7.5 Hz), 7.06 (d, 1 H, J = 7.5 Hz), 7.27-7.45 (m, 5 H). ¹³C NMR (CDCl₃): δ = 14.0, 22.5, 25.5, 28.4, 29.1, 31.6, 39.0, 56.0, 58.0, 96.8, 127.4, 127.8, 128.3, 129.1, 136.4, 153.4, 191.1. HRMS (EI): m/z calcd for C₁₈H₂₅NO (M⁺), 271.1936; found, 271.1942.
1-Benzyl-2,3-dihydro-2-isobutylpyridin-4(1 H )-one (3f) IR (neat): 2960, 1710, 1622, 1575, 1558, 1455, 1352, 1195, 1137, 1059, 970, 738, 699 cm^-1. ¹H NMR (CDCl₃): δ = 0.80 (d, 3 H, J = 6.5 Hz), 0.93 (d, 3 H, J = 6.5 Hz), 1.60 (m, 2 H), 1.79 (m, 1 H), 2.27 (dd, 1 H, J = 3.3 Hz, 16.5 Hz), 2.70 (dd, 1 H, J = 6.7 Hz, 16.7 Hz), 3.5 (m, 1 H), 4.32 (d, 1 H, J = 15.3 Hz), 4.42 (d, 1 H, J = 15.3 Hz), 4.96 (d, 1 H, J = 7.2 Hz), 7.07 (d, 1 H, J = 6.8 Hz), 7.27-7.41 (m, 5 H). ¹³C NMR (CDCl₃): δ = 21.3, 23.4, 24.1, 36.5, 38.3, 53.9, 58.1, 96.0, 127.6, 128.4, 129.1, 136.0, 154.5, 191.3. HRMS (EI): m/z calcd for C₁₆H₂₁NO (M⁺), 243.1623; found, 243.1622.
1-Benzyl-2,3-dihydro-2-isopropylpyridin-4(1 H )-one (3g) IR (neat): 2965, 1713, 1634, 1568, 1558, 1455, 1353, 1195, 1137, 1059, 973, 735, 700 cm^-1. ¹H NMR (CDCl₃): δ = 0.95 (d, 6 H, J = 6.2 Hz), 2.27 (m, 1 H), 2.40 (dd, 1 H, J = 3.5 Hz, 17.0 Hz), 2.63 (dd, 1 H, J = 7.7 Hz, 17.0 Hz), 3.25 (m, 1 H), 4.40 (d, 1 H, J = 15.2 Hz), 4.50 (d, 1 H, J = 15.2 Hz), 4.95 (d, 1 H, J = 7.0 Hz), 7.17-7.40 (m, 6 H), ¹³C NMR (CDCl₃): δ = 17.8, 19.4, 29.0, 35.4, 58.9, 61.0, 96.5, 127.4, 128.4, 129.1, 136.2, 155.8, 192.1. HRMS (EI): m/z calcd for C₁₅H₁₉NO (M⁺), 229.1467; found, 229.1472.