Cerium-catalyzed α-Oxidation of β-Dicarbonyl Compounds with Molecular Oxygen

Abstract

β-Ketoesters and β-diketones are α-hydroxylated by molecular oxygen in the presence of 5 mol% CeCl₃·7 H₂O in i-PrOH as solvent. The method is limited to substrates with an α-alkyl substituent. Optimal yields are achieved with cyclic starting materials.

Key words

catalysis - cerium - β-dicarbonyl compounds - oxidation - oxygen

References

• 1a Crout DHG. Rathbone DL. J. Chem. Soc., Chem. Commun.  1987,  290 
• 1b Crout DHG. Rathbone DL. Synthesis  1989,  40 
• 1c Tamaki K. Shotwell JB. White RD. Drutu I. Petsch DT. Nheu TV. He H. Hirokawa Y. Maruta H. Wood JL. Org. Lett.  2001,  3:  1689 
• 2 Demir AS. Jeganathan A. Synthesis  1992,  235 
• 3 MoO₅ pyridine HMPA: Vedejs E. Engler AD. Telschow JE. J. Org. Chem.  1978,  43:  188 
• 4 Hubert AJ. Starcher PS. J. Chem. Soc. C  1968,  2500 
• 5 Andriamialisoa RZ. Langois N. Langois Y. Tetrahedron Lett.  1985,  26:  3563 
• 6a Adam W. Prechtl F. Chem. Ber.  1991,  124:  2369 
• 6b Adam W. Smerz AK. Tetrahedron  1996,  52:  5799 
• 7a Döbler C. Mehltretter GM. Sundermeier U. Beller M. J. Am. Chem. Soc.  2000,  122:  10289 
• 7b Ferreira EM. Stoltz BM. J. Am. Chem. Soc.  2001,  123:  7725 
• 7c Jensen DR. Pugsley JS. Sigman MS. J. Am. Chem. Soc.  2001,  123:  7475 
• 8 Christoffers J. J. Org. Chem.  1999,  64:  7668 
• 9 Baucherel X. Levoirier E. Uziel J. Juge S. Tetrahedron Lett.  2000,  41:  1385 
• 10 Watanabe T. Ishikawa T. Tetrahedron Lett.  1999,  40:  7795 
• 12 The combination of molecular oxygen and catalytic CeCl₃ is known for oxidation of benzyl alcohol to benzaldehyde in the presence of Pt/C and Bi₂(SO₄)₃: Oi R. Takenaka S. Chem. Lett.  1988,  1115 
• 16a Brenner JE. J. Org. Chem.  1961,  26:  22 
• 16b Hussey CWT. Pinder AR. J. Chem. Soc.  1962,  1517 
• 16c Karrenbrock F. Schäfer HJ. Tetrahedron Lett.  1978,  1521 
• 17 The oxidative dehydrodimerization of malonates with Ce(IV) or Mn(III) under ultrasonic conditions has been reported: Linker T. Linker U. Angew. Chem. Int. Ed.  2000,  39:  902 

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Use of catalytic (10 mol%) amounts of Cs-salts resulted in significantly lower yields.

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Typical Procedure for 2c: Ester 1c (1.09 g, 6.40 mmol) was added to a suspension of CeCl₃·7 H₂O (119 mg, 0.32 mmol) in isopropanol (2.0 mL). The flask was evacuated twice to ca. 500 mbar, flushed with oxygen, and the mixture was then stirred for 16 h under 1 atm of O₂. After filtration through SiO₂ (2 cm, washing with ethyl acetate) and removal of all volatile materials from the filtrate in vacuo 1.14 g (96%, 6.12 mmol) of compound 2c were obtained as a colorless oil. ¹H NMR (CDCl₃, 300 MHz): δ = 1.24-1.32 (m, 1 H), 1.33-1.58 (m, 2 H), 1.67-1.90 (m, 2 H), 1.91-2.05 (m, 1 H), 2.07-2.15 (m, 1 H), 2.27 (dd, J = 14.9 Hz, J = 10.6 Hz, 1 H), 2.59 (ddd, J = 11.7 Hz, J = 7.0 Hz, J = 1.7 Hz, 1 H), 2.96 (td, J = 12.1 Hz, J = 2.9 Hz, 1 H), 3.67 (s, 3 H), 4.35 (s, 1 H) ppm. Anal. Calcd for C₉H₁₄O₄: C, 58.05; H, 7.58. Found: C, 58.27; H, 7.33.

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Selected data for new compounds, Menthyl Ester 2b: ¹H NMR (CDCl₃, 300 MHz), diastereoisomer 1: δ = 0.71 (d, J = 6.8 Hz, 3 H), 0.86 (d, J = 7.4 Hz, 3 H), 0.92 (d, J = 6.4 Hz, 3 H), 0.95-1.13 (m, 2 H), 1.33-1.56 (m, 2 H), 1.63-1.74 (m, 3 H), 1.88-2.17 (m, 5 H), 2.40-2.52 (m, 3 H), 3.86 (s, 1 H), 4.77 (dt, J = 10.5 Hz, J = 7.3 Hz, 1 H) ppm; diastereoisomer 2: δ = 0.77 (d, J = 7.3 Hz, 3 H), 0.90 (d, J = 6.5 Hz, 3 H), 0.92 (d, J = 6.4 Hz, 3 H), 0.95-1.13 (m, 2 H), 1.33-1.56 (m, 2 H), 1.63-1.74 (m, 3 H), 1.88-2.17 (m, 5 H), 2.40-2.52 (m, 3 H), 3.86 (s, 1 H), 4.78 (dt, J = 10.9 Hz, J = 7.3 Hz, 1 H) ppm. ¹³C{¹H}-NMR (CDCl₃, 75 MHz), diastereoisomer 1: δ = 15.92 (CH₃), 18.46 (CH₂), 20.70 (CH₃), 21.94 (CH₃), 23.09 (CH₂), 26.06 (CH), 31.36 (CH), 34.06 (CH₂), 34.96 (CH₂), 36.00 (CH₂), 40.21 (CH₂), 47.02 (CH), 76.85 (CH), 79.71 (C), 171.33 (C=O), 213.38 (C=O) ppm; diastereoisomer 2: δ = 15.99 (CH₃), 18.48 (CH₂), 20.85 (CH₃), 21.89 (CH₃), 23.17 (CH₂), 26.26 (CH), 31.33 (CH), 34.03 (CH₂), 34.63 (CH₂), 35.80 (CH₂), 40.71 (CH₂), 46.95 (CH), 76.90 (CH), 79.70 (C), 171.27 (C=O), 213.43 (C=O) ppm. Mol. mass calcd for C₁₆H₂₆O₄: 282.1831. Found: 282.1831 [M⁺]. Anal. Calcd: C, 68.06; H, 9.28. Found: C, 67.97; H, 9.22. Ethyl 2-benzoyl-2-hydroxypropanoate 2g: ¹H NMR (CDCl₃, 300 MHz): δ = 1.15 (t, J = 7.2 Hz, 3 H), 1.74 (s, 3 H), 4.23 (q, J = 7.1 Hz, 2 H), 4.51 (s, 1 H), 7.42-7.48 (m, 2 H), 7.55-7.60 (m, 1 H), 7.97-8.00 (m, 2 H) ppm. ¹³C{¹H}-NMR (CDCl₃, 75 MHz): δ = 13.81 (CH₃), 23.52 (CH₃), 62.51 (CH₂), 79.48 (C), 128.62 (CH), 129.47 (CH), 133.14 (C), 133.70 (CH), 172.31 (C=O), 195.94 (C=O) ppm. Mol. mass calcd for C₁₂H₁₄O₄: 222.0892. Found: 222.0876 [M⁺]. 3-Benzyl-3-hydroxy-2,4-pentanedione 2i: ¹H NMR (CDCl₃, 300 MHz): δ = 2.23 (s, 6 H), 3.28 (s, 2 H), 4.69 (s, 1 H), 7.19-7.28 (m, 5 H) ppm. ¹³C{¹H}-NMR (CDCl₃, 125 MHz): δ = 25.66 (CH₃), 41.88 (CH₂), 91.06 (C), 127.58 (CH), 128.69 (CH), 130.05 (CH), 134.50 (C), 206.70 (C=O) ppm. Mol. mass calcd for C₁₂H₁₄O₃: 206.0943. Found: 206.0953 [M⁺]. 3-Benzyl-3-chloro-2,4-pentanedione 4b: ¹H NMR (CDCl₃, 300 MHz): δ = 2.15 (s, 6 H), 3.42 (s, 2 H), 7.19-7.22 (m, 2 H), 7.26-7.31 (m, 3 H) ppm. ¹³C{¹H}-NMR (CDCl₃, 125 MHz): δ = 27.39 (CH₃), 42.39 (CH₂), 80.22 (C), 127.55 (CH), 128.37 (CH), 130.69 (CH), 133.88 (C), 201.09 (C=O) ppm. Mol. mass calcd for C₁₂H₁₃ClO₂: 224.0604. Found: 224.0612 [M⁺].

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Formation of by-product 3 was also observed with other procedures. [4] [8]