Mild Michael Addition of Glycine Imines to Aromatic Nitroalkenes Catalyzed by DBU with LiOTf as an Additive

Abstract

A mild Michael addition of glycine imines to aromaticnitroalkenes catalyzed by 10 mol% DBU with LiOTf as an additive was developed. In most cases, the products could be obtained in good yields (up to 96%) with moderate to good diastereoselectivities (up to 10:1). The selectivity for syn adduct can be reversed to anti when the R group of glycine imines was changed from methyl or ethyl to tert-butyl.

Michael addition - nitroalkene - catalysis - amino acids - DBU

References and Notes

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General Procedure for Michael Addition of Glycine Imines to Aromatic Nitroalkenes
To a stirred solution of nitroalkene (1.2 mmol), LiOTf (16 mg, 0.1 mmol), and ethyl diphenylmethyleneiminoacetate (267 mg, 1 mmol) or tert-butyl diphenylmethyleneimino-acetate (295 mg, 1 mmol) in dry THF (1 mL) was added DBU (15 mg, 0.1 mmol) in dry THF (1 mL). The mixture was stirred at r.t. for 24 h. After being quenched by H₂O, the mixture was extracted by CH₂Cl₂. The organic phase was separated and dried with Na₂SO₄. The diastereoselectivity was determined by NMR analysis of curde product. The sample for analysis was purified on column chromatography (SiO₂, 200-300 mesh) using PE-EtOAc (20:1) as eluent and recrystallized from Et₂O and PE.
syn -Ethyl 2-Diphenylmethyleneimino-4-nitro-3-phenyl-butanoate (5a)
According to the general procedure, a white solid was obtained; mp 84-85 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 1.20 (t, J = 7.2 Hz, 3 H), 4.11-4.16 (m, 2 H), 4.27-4.38 (m, 2 H), 5.14-5.18 (m, 2 H), 6.60-6.62 (d, J = 6.9 Hz, 2 H), 7.14-7.48 (m, 1 1H), 7.64 (d, J = 6.9 Hz, 2 H). IR: 1735, 1551, 1446, 1368, 1316, 1290, 1190, 1024, 695 cm^-¹. MS (70 eV, EI): m/z (%) = 416 (3) [M⁺], 343 (10), 296 (23), 267 (21), 266 (100), 193 (47), 165 (50). Anal. Calcd (%) for C₂₅H₂₄N₂O₄: C, 72.10; H, 5.81; N, 6.73. Found: C, 71.74; H, 5.83; N, 6.55.2.
syn -Ethyl 2-Diphenylmethyleneimino-3-(4-methylphenyl)-4-nitrobutanoate (5b)
According to the general procedure, a white solid was obtained; mp 102-103 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 1.19 (t, J = 6.9 Hz, 3 H), 2.29 (s, 3 H), 4.10-4.15 (m, 2 H), 4.27-4.32 (m, 2 H), 5.10-5.12 (m, 2 H), 6.65 (d, J = 6.0 Hz, 2 H), 7.04 (s, 4 H), 7.27-7.45 (m, 6 H), 7.65 (d, J = 7.5 Hz, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 14.0, 21.0, 46.2, 61.5, 68.7, 76.3, 127.3, 128.0, 128.2, 128.3, 128.6, 128.9, 129.3, 130.9, 134.0, 135.4, 137.4, 138.7, 169.9, 172.6. IR: 1736, 1732, 1619, 1552, 1516, 1446, 1379, 1317, 1288, 1182, 1026, 695 cm^-¹. MS (70 eV, EI): m/z (%) = 430 (4) [M⁺], 413 (3), 357 (7), 310 (17), 267 (27), 266 (100), 238 (22), 193 (69), 165 (61). Anal. Calcd (%) for C₂₆H₂₆N₂O₄: C, 72.54; H, 6.09; N, 6.51. Found: C, 72.36; H, 6.22; N, 6.35.