A Yb(OTf)₃/PEG-Supported Quaternary Ammonium Salt Catalyst System for a Three-Component Mannich-Type Reaction in Aqueous Media

Abstract

A one-pot, three-component Mannich reaction of cyclohexanone with aromatic aldehyde and aromatic amine was efficiently catalyzed by Yb(OTf)₃/PEG-supported quaternary ammonium salt system in water at room temperature. This reaction afforded the corresponding β-amino carbonyl compounds in good yields with high anti selectivity, and the catalyst system was recyclable.

ytterbium triflate - poly(ethylene glycol) - Mannich-type reaction - β-amino carbonyl compound - one-pot reaction

References and Notes

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General Procedure for the Synthesis of β-Amino Carbonyl Compound 4
To a mixture of phenylamine (1 mmol), benzaldehyde (1 mmol), and cyclohexanone (1.2 mmol) in H₂O (10 mL) were added PEG-supported ammonium salt 5 (0.3 mmol) and Yb(OTf)₃ (0.01 mmol). The mixture was stirred at r.t. for 2 h, and then extracted with Et₂O (10 mL). The organic phase was dried over anhyd Na₂SO₄ and concentrated. The residue was purified by SiO₂ column with EtOAc-hexane (1:16) as eluent to afford 4, which was rescrystallized from hexane-EtOAc to give analytical pure sample. All products gave satisfactory spectroscopic and analytical data.
Spectral Data of New Compounds
Compound 4c: colorless solid; mp 95-96 ˚C. IR (KBr): 3402, 1701, 1601, 1498, 1446 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.51 (d, J = 9.4 Hz, 1 H), 7.33 (d, J = 9.4 Hz, 1 H), 7.18-7.13 (m, 2 H), 7.02-7.00 (m, 2 H), 6.43-6.40 (m, 2 H), 5.31 (d, J = 7.0 Hz, 1 H), 4.83 (dd, J = 4.7, 7.0 Hz, 1 H), 2.93-2.89 (m, 1 H), 2.35-2.29 (m, 2 H), 2.08-2.00 (m, 2 H), 1.97-1.93 (m, 2 H), 1.77-1.73 (m, 2 H) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 213.4, 145.8, 138.9, 133.5, 129.6, 129.2, 129.1, 128.6, 127.3, 122.3, 114.7, 55.8, 55.4, 43.1, 33.0, 28.4, 25.1 ppm. ESI-MS: m/z = 348 [M + 1]⁺. Anal. Calcd for C₁₉H₁₉Cl₂NO: C, 65.53, H, 5.50, N, 4.02. Found: C, 65.53, H, 5.51, N, 4.03.
Compound 4d: colorless solid; mp 127-128 ˚C. IR (KBr): 3334, 1702, 1598, 1477 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.53 (d, J = 9.2 Hz, 1 H), 7.34 (d, J = 9.2 Hz, 1 H), 7.24-7.13 (m, 2 H), 6.90 (t, J = 8.0 Hz, 1 H), 6.73-6.72 (m, 1 H), 6.68-6.67 (m, 1 H), 6.40-6.38 (m, 1 H), 5.40 (d, J = 8.8 Hz, 1 H), 4.82 (dd, J = 4.7 Hz, J = 8.8 Hz, 1 H), 2.94-2.90 (m, 1 H), 2.34-2.29 (m, 2 H), 2.10-2.07 (m, 1 H), 2.02-2.00 (m, 1 H), 1.97-1.93 (m, 2 H), 1.76-1.73 (m, 2 H) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 213.4, 148.5, 138.8, 133.4, 130.7, 129.6 129.0, 128.7, 127.3, 123.4, 120.6, 116.4, 111.9, 55.6, 55.3, 43.1, 33.1, 28.4, 25.1 ppm. ESI-MS: m/z 392 [M + 1]⁺. Anal. Calcd for C₁₉H₁₉B_rClNO: C, 58.11, H, 4.88, N, 3.57. Found: C, 58.12, H, 4.87, N, 3.58.
Compound 4e: colorless solid; mp 126-127 ˚C. IR (KBr): 3333, 1702, 1599, 1479 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.53 (d, J = 9.4 Hz, 1 H), 7.34 (d, J = 9.4 Hz, 1 H), 7.19-7.14 (m, 2 H), 6.98-6.95 (m, 1 H), 6.59-6.57 (m, 1 H), 6.51-6.47 (m, 1 H), 6.37-6.36 (m, 1 H), 5.40 (s, 1 H), 4.83 (d, J = 3.7 Hz, 1 H), 2.95-2.90 (m, 1 H), 2.34-2.29 (m, 2 H), 2.08-2.01 (m, 2 H), 1.97-1.92 (m, 2 H), 1.76-1.73 (m, 2 H) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 213.4, 148.4, 138.8, 135.1, 133.4, 130.4, 129.6 129.0, 128.7, 127.3, 117.7, 113.4, 111.6, 55.7, 55.4, 43.2, 33.1, 28.4, 25.1 ppm. ESI-MS: m/z = 348 [M + 1]⁺. Anal. Calcd for C₁₉H₁₉Cl₂NO: C, 65.53, H, 5.50, N, 4.02. Found: C, 65.56, H, 5.50, N, 4.06.
Compound 4l: yellow solid (anti/syn = 89:11); mp 137-138 ˚C. IR (KBr): 3364, 1697, 1518, 1346 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ (anti + syn): = 8.14 (d, J = 8.7 Hz, 2 H), 7.58 (d, J = 8.7 Hz, 2 H), 6.89 (d, J = 8.1 Hz, 2 H), 6.42 (d, J = 8.1 Hz, 2 H), 4.82 (s, 0.11 H), 4.74 (s, 0.89 H), 4.68 (s, 0.89 H), 4.46 (m, 0.11 H), 2.84-2.81 (m, 1 H), 2.41-2.29 (m, 2 H), 2.17 (s, 3 H), 2.04-1.98 (m, 2 H), 1.93-1.92 (m, 1 H), 1.77-1.62 (m, 3 H) ppm. ^¹³C NMR (125 MHz, CDCl₃):
δ (major isomer) = 212.0, 150.3, 144.5, 130.0, 128.5, 127.6, 123.9, 113.9, 58.2, 57.3, 42.6, 32.1, 27.9, 24.7, 20.5;
δ (minor isomer) = 210.9, 149.9, 147.2, 129.9, 128.8, 127.8, 123.8, 114.5, 58.1, 56.5, 42.7, 29.2, 27.3, 25.2, 20.5. ppm. ESI-MS: m/z = 359 [M + 1]⁺. Anal. Calcd for C₂₀H₂₂N₂O₃: C, 70.99, H, 6.55, N, 8.28. Found: C, 70.99, H, 6.55, N, 8.26.
Compound 4i: colorless solid; mp 113-114 ˚C. IR (KBr): 1705, 1598, 1515, 1489, 1256 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 7.43-7.40 (m, 2 H), 7.25-7.22 (m, 2 H), 6.78-6.74 (m, 2 H), 6.44-6.41 (m, 2 H), 4.75 (s, br, 1 H), 4.49 (d, J = 6.6 Hz, 1 H), 2.72-2.70 (m, 1 H), 2.42-2.39 (m, 1 H), 2.34-2.31 (m, 1 H), 1.98-1.89 (m, 2 H), 1.88-1.85 (m, 1 H), 1.75-1.63 (m, 3 H) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ = 212.7, 157.1 (d, J _C-F = 234.4 Hz), 143.5, 140.8, 131.8, 129.3, 121.2, 115.7 (d, J _C-F = 22.5 Hz), 114.9 (d, J _C-F = 7.5 Hz), 58.7, 57.4, 42.4, 31.8, 28.1, 24.3 ppm. ESI-MS: m/z 399
[M + Na]⁺. Anal. Calcd for C₁₉H₁₉BrFNO: C, 60.65, H, 5.09, N, 3.72. Found: C, 60.70, H, 5.12, N, 3.70.
Compound 4g: colorless solid (anti/syn = 98:2); mp 112-113 ˚C. IR (KBr): 1700, 1599, 1523, 1489, 1247 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ (anti + syn) = 7.30-7.25 (m, 4 H), 7.78-7.74 (m, 2 H), 6.44-6.41 (m, 2 H), 6.66 (d, J = 4.0 Hz, 0.02 H), 4,65 (br s, 1 H), 4.50 (d, J = 6.6 Hz, 0.98 H), 2.72-2.69 (m, 1 H), 2.42-2.29 (m, 2 H), 1.99-1.95 (m, 1 H), 1.88-1.75 (m, 3 H), 1.67-1.63 (m, 2 H) ppm. ^¹³C NMR (125 MHz, CDCl₃): δ (major isomer) = 212.6, 157.1 (d, J _C-F = 234.0 Hz), 143.6, 140.4, 133.1, 128.9, 128.8, 115.7 (d, J _C-F = 22.0 Hz), 114.9 (d, J _C-F = 7.4 Hz), 58.6, 57.5, 42.3, 31.8, 28.1, 24.3; δ (minor isomer) = 211.4, 157.1 (d, J _C-F = 234.0 Hz), 143.6, 140.4, 133.1, 129.2, 128.8, 115.6 (d, J _C-F = 22.4 Hz), 115.3 (d, J _C-F = 7.5 Hz), 57.8, 56.6, 42.6, 28.8, 27.2, 25.1 ppm. ESI-MS: m/z = 355 [M + Na]⁺. Anal. Calcd for C₁₉H₁₉ClFNO: C, 68.77, H, 5.77, N, 4.22. Found: C, 68.79, H, 5.78, N, 4.22.