Dimethyldioxirane Oxidation of 2-Silyloxypyrroles: An Efficient Regiocontrolled Synthesis of 5-Hydroxy-3-pyrrolin-2-ones

Abstract

A new method for the synthesis of 5-hydroxy-3-pyrrolin-2-ones is reported. Conversion of N-Boc-3-pyrrolin-2-ones into 2-triisopropylsilyloxypyrroles and ensuing oxidation with dimethyldioxirane provides the corresponding N-Boc-5-hydroxy-3-pyrrolin-2-ones in high yields.

alkaloids - lactams - oxyfunctionalization - regioselectivity - Wittig reaction

References and Notes

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13

Typical Procedure: To a solution of 4a (732 mg, 4.0 mmol) in anhyd CH₂Cl₂ (5 mL) were added 2,6-lutidine (1.290 g, 12.0 mmol) and TIPSOTf (1.232 g, 4.54 mmol) under nitrogen at r.t. After stirring for 30 min, the solvent was evaporated and the residue was purified by flash chromatog-raphy on silica gel (hexanes-EtOAc, 95:5) to give 5a (1.263 g, 93%) as a colorless oil. For smaller-scale reactions, purification was carried out by chromatography on basic silica gel.^11c
Data for 5a: ¹H NMR (300 MHz, CDCl₃): δ = 1.10 (d, J = 7.2 Hz, 18 H), 1.25 (hept, J = 7.2 Hz, 3 H), 1.54 (s, 9 H), 5.21 (dd, J = 1.7, 3.6 Hz, 1 H), 5.86 (dd, J = 1.7, 3.6 Hz, 1 H), 6.67 (t, J = 3.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 12.4, 17.9, 27.8, 82.4, 91.7, 107.6, 112.5, 143.6, 148.1. HRMS: m/z calcd for C₁₈H₃₃NO₃Si: 339.2230; found: 339.2233.

14a Adam W. Bialas J. Hadjiarapoglou L. Chem. Ber.  1991,  124:  2377 

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15

Typical Procedure: To a solution of 5a (339 mg, 1.0 mmol) in anhyd CH₂Cl₂ (5 mL) at -78 °C was added dropwise a solution of DMDO (0.055 M in acetone, 20 mL, 1.1 equiv) and the reaction mixture was stirred for 1 h at -78 °C. The volatiles were evaporated and the residue was dissolved in acetone (10 mL). After addition of H₂O (7 mL) and Amberlyst-15 (ca. 100 mg), the reaction mixture was stirred for 1 h at r.t. The mixture was filtered, the filtrate was extracted with Et₂O (3 × 10 mL) and the combined organic layers were dried over anhyd MgSO₄. After evaporation of the volatiles, the residue was purified by flash chromatog-raphy on silica gel (hexanes-EtOAc, 7:3) to furnish 6a (187 mg, 94%) as a white solid (mp 100-101 °C). ¹H NMR (300 MHz, CDCl₃): δ = 1.54 (s, 9 H), 4.32 (br d, J = 4.8 Hz, 1 H), 5.96 (br m, 1 H), 6.07 (d, J = 6.4 Hz, 1 H), 7.02 (dd, J = 4.8, 6.4 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.0, 82.0, 83.8, 128.3, 146.3, 149.9, 166.4. Anal. Calcd for C₉H₁₃NO₄: C, 54.26; H, 6.58; N, 7.03. Found: C, 54.62; H, 6.53; N, 7.00.

16 Epoxides have been obtained from reactions of DMDO with indoles: Zhang X. Foote CS. J. Am. Chem. Soc.  1993,  115:  8867 

17

Data for 6f: mp 62-64 °C. ¹H NMR (300 MHz, CDCl₃): δ = 1.53 (s, 9 H), 1.54 (br s, 3 H), 1.63 (br s, 3 H), 2.74 (dd, J = 6.8, 14.5 Hz, 1 H), 2.90 (dd, J = 8.3, 14.5 Hz, 1 H), 4.42 (br s, 1 H), 4.86 (dd, J = 6.8, 8.3 Hz, 1 H), 6.03 (d, J = 6.0 Hz, 1 H), 7.00 (d, J = 6.0 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 17.8, 25.7, 27.8, 36.5, 83.7, 92.6, 116.2, 126.6, 136.4, 145.3, 150.3 (2 × C), 166.6. Anal. Calcd for C₁₄H₂₁NO₄: C, 62.90; H, 7.92; N, 5.24. Found: C, 62.84; H, 7.87; N, 5.16.

18 For the removal of the Boc group from compounds 6b,c using neat TFA at 0 °C, see: Yakushijin K. Suzuki R. Hattori R. Furukawa H. Heterocycles  1981,  16:  1157 

19 Masuko M. Miyamoto K. Sakurai K. Iino M. Takeuchi Y. Hashimoto T. Phytochemistry  1983,  22:  1278 

20

Data for 8: colorless oil. ¹H NMR (300 MHz, CDCl₃): δ = 1.27 (t, J = 7.0 Hz, 3 H), 1.45 (s, 9 H), 2.00 (s, 3 H), 4.20 (q, J = 7.0 Hz, 2 H), 6.78 (d, J = 11.7 Hz, 1 H), 6.91 (dd, J = 11.7, 11.7 Hz, 1 H), 7.69 (br s, 1 H), 8.11 (d, J = 11.7 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 12.6, 14.1, 27.8, 60.8, 82.6, 123.6, 132.3, 135.3, 137.3, 150.3, 165.5, 167.8. HRMS: m/z [M + H⁺] calcd for C₁₄H₂₂NO₅: 284.1498; found: 284.1502.