Selective Addition of Carbamoylsilane to Vicinal Diketones: Highly Efficient Synthesis of β-Keto-α-hydroxyamides

Abstract

The selective addition of carbamoylsilane to vicinal diketones in toluene solvent at 110 °C affords β-keto-α-siloxyamide derivatives in good yields (54–99%). The steric hindrance is an important factor in the addition reaction.

Keywords

diketones - carbamoylsilane - amides - addition - synthetic methods

• References and Notes

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• 10 General Procedure for the Preparation of β-keto-α-Siloxyamides 3 or 5 A Schlenk tube fitted with a Teflon vacuum stopcock and micro stirbar was flame-heated under vacuum and refilled with Ar. Vicinal diketones 2 (0.50 mmol) and 1.5 mL of anhydrous toluene was added at ice bath temperature. After 20 min, 1.2 equiv of carbamoylsilane (0.60 mmol) was added, and the reaction mixture was stirred at 110 °C until complete consumption of the carbamoylsilane (TLC). Volatiles were then removed under vacuum and the residue was chromatographed using PE–EtOAc as eluent to obtain β-keto-α-siloxyamides 3 (or 5). Characterization Data for Typical β-Keto-α-siloxyamides All NMR spectra were obtained in CDCl₃ unless otherwise indicated. Compound 3a: white solid; yield 99% (176 mg, 0.5 mmol); mp 125.0–127.0 °C. IR: 1651, 1395, 1245, 1112 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 7.87–7.32 (m, 10 H), 3.00 (s, 3 H), 2.85 (s, 3 H), 0.11 (s, 9 H). ¹³C NMR (151 MHz, CDCl₃): δ = 197.2, 170.6, 139.1, 136.0, 132.2, 130.0, 128.3, 128.0, 127.8, 88.7, 38.3, 36.9, 2.0. Anal. Calcd for C₂₀H₂₅NO₃Si: C, 67.57; H, 7.09; N, 3.94. Found: C, 67.31; H, 7.13; N, 3.77. Compound 3d: colorless liquid, yield 63% (85 mg, 0.52 mmol). IR: 1719, 1651, 1390, 1252, 1150, 1099, 1058 cm^–1. ¹H NMR: δ = 2.93 (s, 3 H), 2.89 (s, 3 H), 2.21, 1.57 (ss, 3 H), 2.67–1.17 (m, 4 H), 0.92 (t, J = 7.2 Hz, 3 H), 0.17, 0.16 (ss, 9 H). ¹³C NMR: δ = 210.0, 207.7, 170.2, 169.7, 87.4, 84.7, 39.4, 37.9, 37.4, 37.3, 36.7, 36.6, 25.6, 24.5, 17.0, 16.9, 14.3, 13.7, 1.6, 1.5. Anal. Calcd for C₁₂H₂₅NO₃Si: C, 55.56; H, 9.71; N, 5.40. Found: C, 55.64; H, 9.55; N, 5.31. Compound 3e: yellowish solid, yield 63% (92 mg, 0.5 mmol), mp 82.0–83.0 °C. IR: 1731, 1639, 1395, 1253, 1182, 1132 cm^–1. ¹H NMR: δ = 7.39–7.33 (m, 5 H), 3.00, 2.99 (ss, 3 H), 2.78, 2.77 (ss, 3 H), 2.05, 2.04 (ss, 3 H), 0.23, 0.22 (ss, 9 H). ¹³C NMR: δ = 204.0, 171.0, 139.1, 128.8, 128.4, 125.8, 88.6, 38.3, 36.1, 27.6, 2.3, 2.1, 1.9. Anal. Calcd for C₁₅H₂₃NO₃Si: C, 61.40; H, 7.90; N, 4.77. Found: C, 61.18; H, 7.61; N, 4.65. Compound 3f: colorless liquid, yield 89% (115 mg, 0.49 mmol). IR: 3353, 1686, 1640, 1366, 1235, 1129, 1048, 691 cm^–1. ¹H NMR: δ = 8.02–7.41 (m, 5 H), 3.00 (s, 3 H), 2.85 (s, 3 H), 2.79 (s, 1 H), 2.12, 2.11 (dd, J = 1.8 Hz, 2 H), 1.75–1.72 (m, 1 H), 0.93 (d, J = 6.6 Hz, 3 H), 0.89 (d, J = 6.6 Hz, 3 H). ¹³C NMR: δ = 197.6, 171.3, 134.6, 133.5, 129.5, 128.9, 128.6, 125.9, 81.7, 44.1, 37.7, 37.2, 24.6, 23.9, 23.4, 22.2. Anal. Calcd for C₁₅H₂₁NO₃: C, 68.42, H,8.04, N, 5.32. Found: C, 68.20; H, 7.98; N, 5.57. Compound 5c: yellowish liquid, yield 64% (90 mg, 0.51 mmol). IR: 1723, 1663, 1458, 1393, 1253, 1151 cm^–1. ¹H NMR: δ = 5.02–4.48 (m, 2 H), 3.33, 3.32, 3.21, 3.19 (ssss, 3 H), 2.97, 2.94, 2.89, 2.85 (ssss, 3 H), 2.83–2.05 (m, 2 H), 2.26, 2.17, 1.63, 1.60 (ssss, 3 H), 1.09, 0.92 (tt, J = 7.8 Hz, 3 H), 0.20, 0.18 (ss, 9 H). ¹³C NMR: δ = 211.3, 207.8, 171.8, 88.7, 84.9, 80.4, 80.3, 79.1, 78.9, 56.1, 56.0, 55.2, 34.1, 33.8, 33.5, 30.1, 29.8, 29.7, 29.2, 25.7, 25.4, 24.5, 8.4, 8.1, 7.7, 7.6, 1.8, 1.7. Anal. Calcd for C₁₂H₂₅NO₄Si: C, 52.33; H, 9.15; N, 5.09. Found: C, 52.58; H, 9.36; N, 5.30. Compound 5f: yellowish liquid, yield 71% (130 mg, 0.50 mmol). IR: 1655, 1446, 1393, 1251, 1104 cm^–1. ¹H NMR: δ = 7.45–7.35 (m, 5 H), 4.88–4.36 (m, 2 H), 3.41, 2.97 (ss, 3 H), 2.77, 2.69 (ss, 3 H), 2.65–2.57 (m, 1 H), 2.06–1.87 (m, 2 H), 0.88, 0.85 (dd, J = 6.6 Hz, 3 H), 0.55, 0.51 (dd, J = 6.6 Hz, 3 H), 0.26, 0.23 (ss, 9 H). ¹³C NMR: δ = 197.3, 195.8, 172.1, 135.1, 132.9, 132.6, 129.8, 128.5, 128.4, 128.2, 128.1, 126.3, 125.9, 87.1, 86.7, 80.1, 79.5, 56.4, 55.2, 46.7, 34.2, 33.9, 24.2, 24.1, 24.0, 22.4, 22.3, 1.9. Anal. Calcd for C₁₉H₃₁NO₄Si: C, 62.43; H, 8.55; N, 3.83. Found: C, 62.28; H, 8.75; N, 3.62. Compound 3b: colorless liquid, yield 86% (102 mg, 0.51 mmol). Compound 3c: colorless liquid, yield 72% (87 mg, 0.49 mmol). Compound 3e′: colorless liquid, yield 32% (45 mg, 0.5 mmol). Compound 5a: yellowish liquid, yield 93% (179 mg, 0.50 mmol). Compound 5b: colorless liquid, yield 72% (96 mg, 0.51 mmol). Compound 5d: colorless liquid, yield 54% (78 mg, 0.50 mmol). Compound 5e: colorless liquid, yield 52% (82 mg, 0.49 mmol). Compound 5e′: slightly brown liquid, yield 24% (38 mg, 0.49 mmol).