Synthesis of β-Amino Esters via Aza-Michael Addition of Amines to Alkenes Promoted on Silica: A Useful and Recyclable Surface

Abstract

A solvent-free protocol for the synthesis of β-amino ­esters and nitriles has been developed via conjugate addition of amines to electron-deficient alkenes promoted on silica. The silica surface may be recycled. Both aliphatic and aromatic primary or secondary amines worked efficiently to yield the desired adducts in good to excellent yields.

aza-Michael addition - amines - conjugated alkenes - β-amino esters - silica gel

References

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<A NAME="RD11104ST-14">14</A>

General Procedure for the Aza-Michael Addition Reaction: A mixture of the amine (2 mmol) and alkene (5 mmol) was added to activated [by heating silica gel (10 g) at 120-130 °C for 10 min under vacuum (0.5 mm Hg) and then cooled under N₂] silica (1 g; E. Merck; silica gel HF₂₅₄ for TLC) and stirred at the appropriate temperature for several hours (see Table [1] ). TLC monitoring showed in most cases that the reaction was complete. The solid surface was then taken in MeOH, filtered off and the filtrate was concentrated to afford the crude products. Pure products were isolated by chromatography on a silica gel column eluting with various ratios of EtOAc to light petroleum. They were identified by IR, ¹H NMR and ¹³C NMR spectral data.

<A NAME="RD11104ST-15">15</A>

Selected NMR (300 MHz, CDCl ₃ ) Spectral Data for the Adducts:Entry 6: ¹H NMR: δ = 0.98 (d, 12 H, J = 6.6 Hz), 1.24 (t, 3 H, J = 7.1 Hz), 2.38 (t, 2 H, J = 7.1 Hz), 2.75 (t, 2 H, J = 7.1 Hz), 2.99 (sep, 2 H, J = 6.6 Hz), 4.10 (q, 2 H, J = 7.1 Hz). ¹³C NMR: δ = 14.2, 20.6, 36.6, 41.1, 48.3, 60.0, 172.9.
Entry 9: ¹H NMR: δ = 1.02-1.31 (m, 10 H), 1.60-1.77 (m, 10 H), 2.34 (t, 2 H, J = 7.1 Hz), 2.47-2.55 (m, 2 H), 2.87 (t, 2 H, J = 7.1 Hz). ¹³C NMR: δ = 20.6, 26.0, 32.1, 42.6, 58.3, 119.3.
Entry 10: ¹H NMR: δ = 1.06-1.28 (m, 6 H), 1.26 (t, 6 H, J = 7.1 Hz), 1.59-1.78 (m, 4 H), 2.37-2.43 (m, 1 H), 2.41 (t, 4 H, J = 7.1 Hz), 2.79 (t, 4 H, J = 7.1 Hz), 4.11 (q, 4 H, J = 7.1 Hz). ¹³C NMR: δ = 14.2, 26.1, 26.2, 29.1, 34.8, 46.2, 60.2, 172.7.
Entry 13: ¹H NMR: δ = 2.60 (t, 2 H, J = 6.5 Hz), 3.46 (t, 2 H, J = 6.5 Hz), 3.75 (s, 3 H), 6.60 (d, 2 H, J = 8.9 Hz), 6.80 (d, 2 H, J = 8.9 Hz). ¹³C NMR: δ = 18.1, 40.8, 55.7, 114.8, 115.0, 118.2, 140.0, 153.9.
Entry 18: ¹H NMR: δ = 1.25 (t, 3 H, J = 7.1 Hz), 1.73 (t, 4 H, J = 5.8 Hz), 2.49 (t, 2 H J = 6.9 Hz), 2.55 (t, 4 H, J = 5.8 Hz), 2.72 (t, 2 H, J = 6.9 Hz), 3.94 (s, 4 H), 4.13 (q, 2 H, J = 7.1 Hz). ¹³C NMR: δ = 14.1, 32.5, 34.7, 50.9, 53.1, 60.3, 64.1, 106.9, 172.5.