Rearrangement of Pyran Derivatives Obtained from Vinyl Malononitriles and Aldehydes via Vinylogous Aldol Reaction: A Novel Facile Method for the Synthesis of Dienamides

Abstract

A novel one-pot approach to a variety dienamides from vinyl malononitriles and aldehydes via vinylogous aldol reaction was achieved by the electrolytic ring opening of the initially formed pyran derivatives under mild basic catalysis with good diastereoselectivity.

Key words

vinyl malononitrile - vinylogous aldol reaction - pyran rearrangement - dienamides

References

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General Procedure for the Synthesis of Dienamide 3a
The mixture of vinyl malononitrile 1a (1.5 mmol), aldehyde 2a (1 mmol), and Et₃N (1 mmol) in ethylene glycol (7 mL) was stirred at 40 ˚C for 40 min. After the reaction was complete as indicated by TLC, the reaction mixture was cooled to r.t. diluted with acid H₂O (10 mL). The resulting precipitate was filtered and subjected to chromatographic purification over silica gel (Merck; 100-200 mesh; EtOAc-hexane = 3:7) to obtain dienamide 3a (78%) as a single diastereomer.
Spectral Data of Dienamide 3a (Table 1, Entry 1) Off-white solid; yield 78%; mp 392 ˚C. ^¹H NMR (500 MHz, DMSO-d ₆): δ = 1.55 (m, 2 H), 1.75 (m, 2 H), 2.53 (m, 4 H), 6.42 (s, 1 H), 7.21 (d, J = 8.4 Hz, 2 H), 7.38 (d, J = 8.4 Hz, 2 H), 7.53 (s, 1 H, D₂O exchangeable), 7.87 (s, 1 H, D₂O exchangeable). ^¹³C NMR (125 MHz, DMSO-d ₆): δ = 26.0, 26.4, 29.9, 35.1, 106.6, 116.8, 127.2, 128.9, 128.9, 130.1, 131.4, 132.6, 135.0, 139.3, 164.3, 164.5. IR (KBr): ν_max = 3397, 3385, 2935, 2216, 1673, 1388, 1092, 626 cm^-¹. ESI-MS: 287 [M + 1]. Anal. Calcd (%) for C₁₆H₁₅ClN₂O: C, 67.02; H, 5.27; N, 9.77. Found: C, 66.97; H, 5.21; N, 9.71.
Spectral Data of Dienamide 3k (Table 1, Entry 11) Off-white solid; yield 80%; mp 364 ˚C. ^¹H NMR (500 MHz, CDCl₃): δ = 0.89 (t, J = 6.9 Hz, 3 H), 1.32 (m, 4 H), 1.47 (m, 2 H), 1.64 (m, 2 H), 2.82 (t, J = 8.4 Hz, 2 H), 5.87 (s, 1 H, D₂O exchangeable), 6.33 (s, 1 H, D₂O exchangeable), 7.17 (d, J = 16.9 Hz, 1 H), 7.69 (d, J = 8.4 Hz, 2 H), 8.22 (d, J = 8.4 Hz, 2 H), 8.58 (d, J = 16.1 Hz. 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 14.1, 22.5, 29.5, 30.3, 31.4, 33.8, 105.6, 117.8, 124.2, 124.2, 128.0, 128.7, 128.7, 137.1, 141.9, 148.2, 163.1, 166.0. IR (KBr): ν_max = 3358, 3187, 2930, 2217, 1670, 1600, 1521, 1338 cm^-¹. ESI-MS: 328 [M + 1]. Anal. Calcd (%) for C₁₈H₂₁N₃O₃: C, 66.04; H, 6.47; N, 12.84. Found: C, 66.01; H, 6.43; N, 12.77.

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Crystallographic data for compound 3a in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplemental publication No. CCDC- 775677. Copies of the data can be obtained, free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone] or email: [e-mail]].