Ammonia in Ugi-Smiles and Ugi Couplings

Abstract

Ammonia may be used in Ugi-type reactions, providing good yields of Ugi-Smiles and Ugi-Mumm adducts under microwave irradiation.

Key words

ammonia - Ugi-Smiles - isocyanide - multicomponent couplings

References and Notes

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12

Typical Procedure for 1: In a microwave tube were introduced MeOH (1.0 mL), 2-nitrophenol (140 mg, 1.0 mmol), a 30% aq solution of NH₃ (120 µL, 1.5 equiv), isovaleraldehyde (108 µL, 1.0 equiv), and p-chlorobenzyl-isocyanide (150 µL, 1.0 equiv). The reaction mixture was stirred for 90 min under microwave irradiation (100 W, 130 ˚C). The solvent was then removed under reduced pressure to afford the Ugi-Smiles product after purification by flash column chromatography on silica gel (244 mg, 65% yield); mp 91-92 ˚C. ^¹H NMR (400 MHz, CDCl₃): δ = 8.22 (dd, 1 H, J = 8.6, 1.4 Hz), 8.07 (d, 1 H, J = 4.5 Hz), 7.48 (ddd, 1 H, J = 8.4, 7.1, 1.4 Hz), 7.24 (dt, 2 H, J = 8.6, 2.3 Hz), 7.09 (d, 2 H, J = 8.6 Hz), 6.84 (ddd, 1 H, J = 8.6, 7.1, 1.3 Hz), 6.76 (d, 1 H, J = 8.4 Hz), 6.72 (t, 1 H, J = 5.9 Hz), 4.43 (dd, 1 H, J = 15.3, 5.9 Hz), 4.38 (dd, 1 H, J = 15.3, 5.9 Hz), 4.01 (dt, 1 H, J = 9.3, 4.5 Hz), 1.98-1.75 (m, 3 H), 1.05 (d, 3 H, J = 6.2 Hz), 0.95 (d, 3 H, J = 6.2 Hz). ^¹³C NMR (100.6 MHz, CDCl₃): δ = 173.1, 144.3, 137.1, 136.8, 133.8, 133.6, 129.3, 129.2, 127.4, 118.0, 115.0, 58.1, 43.0, 42.7, 25.6, 23.6, 21.8. HRMS: m/z calcd for C₁₉H₂₂ClN₃O₃: 375.1350; found: 375.1352.