Highly Efficient Aza-Michael Reactions of Enones with Carbamates Using a Combination of Quaternary Ammonium Salts and BF₃·OEt₂ as a Catalyst

Abstract

Aza-Michael reactions of enones with carbamates took efficiently in the presence of a catalytic amount of quaternary ammonium salts and BF₃·OEt₂ to afford the total products in high yields. The new catalytic system was also efficient in the aza-Michael reaction of chalcone, which was difficult to react with carbamates by transition metal salts catalysts.

quaternary ammonium salts - Lewis acids - Michael reaction - carbamate - enone

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Representative Experimental Procedure:
TBAB (0.1 mmol) and the enones (1 mmol) were dissolved in CH₂Cl₂ (3 mL). BF₃·OEt₂ (0.2 mmol) was added. Then carbamate (1.2 mmol) was added in one portion. The mixture solution was stirred at r.t. and conversion was monitored by TLC (for 24 h). After completion of the reaction, the mixture was quenched with sat. aq NaHCO₃ (5 mL), and the aq layer was extracted with CH₂Cl₂. The combined organic layers were dried over Na₂SO₄, filtered, and evaporated. The crude product was purified by column chromatography (eluting solvent: EtOAc-petroleum ether). All the compounds were identified by GC-MS (Agilent 6890N GC/5973N MS, HP-5MS) and usual spectral methods. Selected spectral data of new compounds. 4a: IR(solid): 3366, 3029, 2965, 1721, 1681, 1526, 1291, 1241, 1221, 1022, 746, 699 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.88 (d, J = 7.2 Hz, 2 H), 7.54 (t, J = 7.2 Hz, 1 H), 7.44-7.22 (m, 12 H), 5.89 (br s, 1 H), 5.33 (d, J = 6.0 Hz, 1 H), 5.09 (s, 2 H), 3.68 (dd, J = 16.7 Hz, J = 4.2 Hz, 1 H), 3.45 (dd, J = 16.7 Hz, J = 4.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.8, 155.7, 141.2, 136.6, 136.3, 133.4, 128.6, 128.5, 128.1, 127.5, 126.3, 66.8, 51.8, 43.9. GC-MS: m/z = 359. 4f: ¹H NMR: δ = 7.95 (d, J = 7.2 Hz, 2 H), 7.54 (t, J = 7.2 Hz, 1 H), 7.45-7.24 (m, 7 H), 5.36 (dd, J ₁ = 6.0 Hz, J ₂ = 8.6 Hz, 1 H), 4.22 (dd, J ₁ = 1.6 Hz, J ₂ = 8.8 Hz, 1 H), 3.57 (br s, 2 H), 3.43 (dd, J ₁ = 8.0Hz, J ₂ = 16.0 Hz, 1 H): ¹³C NMR: δ = 197.2, 157.9, 138.7, 136.6, 133.7, 129.1, 129.0, 128.4, 127.5, 62.2, 54.6, 43.4, 40.6. 4g: ¹H NMR: δ = 7.88 (d, J = 7.2 Hz, 2 H), 7.57 (m, 1 H), 7.41 (m, 2 H),7.24 (m, 2 H), 6.81 (m, 2 H), 5.63 (br s, 1 H), 5.22 (dd, J ₁ = 6.4 Hz, J ₂ = 14.0 Hz, 1 H), 4.07 (dd, J ₁ = 6.8 Hz, J ₂ = 14.0 Hz, 2 H), 3.64-3.74 (m, 2 H), 3.37-3.43 (m, 1 H), 1.20 (t, J ₁ = 6.4 Hz, J ₂ = 15.2 Hz, 3 H). ¹³C NMR: δ = 198.2, 159.0, 156.1, 136.9, 133.7, 133.6, 128.9, 128.3, 127.8, 114.2, 61.1, 55.5, 51.5, 44.3, 14.8. 4h: ¹H NMR: δ = 7.88 (d, J = 7.2 Hz, 2 H), 7.55-7.21 (m, 8 H), 5.72 (br s, 1 H), 5.28 (dd, J ₁ = 6.4 Hz, J ₂ = 14.0 Hz, 1 H), 3.67 (m, 2 H), 3.40-3.46 (m, 1 H), 1.21 (t, J ₁ = 6.4 Hz, J ₂ = 14.0 Hz, 3 H). ¹³C NMR: δ = 198.2, 159.8, 156.2, 141.6, 136.8, 133.6, 128.9, 128.3, 127.7, 61.2, 51.9, 44.2, 14.8. 4i: ¹H NMR: δ = 7.85 (d, J = 7.2 Hz, 2 H), 7.57-7.20 (m, 12 H), 6.00 (br s, 1 H), 5.26 (dd, J ₁ = 6.0 Hz, J ₂ = 13.2 Hz, 1 H), 4.77 (br s, 2 H), 3.65 (m, 1 H), 3.40 (dd, J = 5.2 Hz, J = 16.8 Hz, 1 H). ¹³C NMR: δ = 197.9, 157.0, 156.0, 140.7, 136.6, 136.5, 133.9, 132.0, 129.0, 128.7, 128.5, 128.3, 127.9, 121.5, 67.1, 51.4, 43.8.