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Volumn 15, Issue 16, 2009, Pages 3960-3964

Enantioselective synthesis of 2-isoxazolines by a One-flask conjugate addition/oxime-transfer process

Author keywords

Amines; Asymmetric Catalysis; Cyclization; Enantioseleclivity; Isoxazolines

Indexed keywords

ACETONE OXIMES; AQUEOUS SOLUTIONS; ASYMMETRIC CATALYSIS; BENZOIC ACIDS; CATALYTIC SPECIES; ENANTIO-SELECTIVE SYNTHESIS; ENANTIOSELECLIVITY; ENANTIOSELECTIVE; FLASH CHROMATOGRAPHIES; ISOXAZOLINES; ORGANIC CATALYSTS; ORGANIC EXTRACTS; REACTION MIXTURES; STARTING MATERIALS; STRONG ACIDS; TRANSFER PROCESS; UNSATURATED ALDEHYDES;

EID: 65349110328     PISSN: 09476539     EISSN: 15213765     Source Type: Journal    
DOI: 10.1002/chem.200802684     Document Type: Article
Times cited : (41)

References (39)
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    • for selected examples of 2-isoxazolines for the construction of aldol and 1,3-amino alcohol functionalities, see
    • b) A. Bãdoiu, Y. Brinkmann, F. Viton, E. P. Kündig, Pure Appl Chem. 2008, 80, 1013-1018; for selected examples of 2-isoxazolines for the construction of aldol and 1,3-amino alcohol functionalities, see:
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    • Attempts to convert 1a to the corresponding 2-isoxazoline by using acetone oxime with 20 mol% of catalyst 5 together with various acids resulted in racemic products at room temperature. When the reaction was conducted at- 20°C and sulfonic acids (MsOH or p-TsOH) were used as cocatalysts, moderate (ca. 60 %) ee values were obtained, but the yields were below 20%.
    • Attempts to convert 1a to the corresponding 2-isoxazoline by using acetone oxime with 20 mol% of catalyst 5 together with various acids resulted in racemic products at room temperature. When the reaction was conducted at- 20°C and sulfonic acids (MsOH or p-TsOH) were used as cocatalysts, moderate (ca. 60 %) ee values were obtained, but the yields were below 20%.
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    • It should be noted that a perfectly enantioselective catalyst could not be responsible for the nearly complete racemization of the intermediate. However, equilibration with a less-than-perfect catalyst will unavoidably result in the erosion of enantiomeric purity
    • It should be noted that a perfectly enantioselective catalyst could not be responsible for the nearly complete racemization of the intermediate. However, equilibration with a less-than-perfect catalyst will unavoidably result in the erosion of enantiomeric purity.
  • 30
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    • 1H NMR spectra and the decomposition of 1b was most reliably detected with the use of an internal standard (see the Supporting Information).
    • 1H NMR spectra and the decomposition of 1b was most reliably detected with the use of an internal standard (see the Supporting Information).
  • 31
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    • Apparently, the salts resulting from the combination of relatively weak bases, such as anilines or imidazolidinones, with moderately strong acids, such as TFA or diphenylphosphoric acid, are acidic enough to activate cyclization. Stronger bases, such as pyrrolidine or its derivatives, form salts that are weaker acids and thus poor catalysts for the cyclization process
    • Apparently, the salts resulting from the combination of relatively weak bases, such as anilines or imidazolidinones, with moderately strong acids, such as TFA or diphenylphosphoric acid, are acidic enough to activate cyclization. Stronger bases, such as pyrrolidine or its derivatives, form salts that are weaker acids and thus poor catalysts for the cyclization process.
  • 32
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    • Previously reported examples of acid-promoted oxime transfer reactions require harsher conditions and longer reaction times, see: a P. A. Jacobi, M. Martinelli, E. C. Taylor, J. Org. Chem. 1981, 46, 5416-5417;
    • Previously reported examples of acid-promoted oxime transfer reactions require harsher conditions and longer reaction times, see: a) P. A. Jacobi, M. Martinelli, E. C. Taylor, J. Org. Chem. 1981, 46, 5416-5417;
  • 34
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    • Other catalysts were also screened for this transformation. The diphenyl analoge of 6 Hayashi catalyst see: Y. Hayashi, H. Gotoh, T. Hayashi, M. Shoji, Angew. Chem. 2005, 117, 4284-4287;
    • Other catalysts were also screened for this transformation. The diphenyl analoge of 6 (Hayashi catalyst see: Y. Hayashi, H. Gotoh, T. Hayashi, M. Shoji, Angew. Chem. 2005, 117, 4284-4287;
  • 35
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    • 2COOH gave a significantly lower yield and enantioselectivity (40% yield, 45% ee).
    • 2COOH gave a significantly lower yield and enantioselectivity (40% yield, 45% ee).
  • 36
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    • 2O/HCl system typically displayed slightly higher yields of the isoxazoline product. However, the isolated products were often contaminated with minor impurities that complicated the HPLC analysis.
    • 2O/HCl system typically displayed slightly higher yields of the isoxazoline product. However, the isolated products were often contaminated with minor impurities that complicated the HPLC analysis.
  • 37
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    • The yield of 4a is largely limited by competing polymerization of 1a in the reaction conditions.
    • The yield of 4a is largely limited by competing polymerization of 1a in the reaction conditions.
  • 38
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    • Examples of asymmetric conjugate additions of oxygen nucleophiles to enals are rare. Addition of salicylaldehydes to enals preserves the aldehyde oxidation state but does not preserve the original functionality, see: a
    • Examples of asymmetric conjugate additions of oxygen nucleophiles to enals are rare. Addition of salicylaldehydes to enals preserves the aldehyde oxidation state but does not preserve the original functionality, see: a) T. Govender, L. Hojabri, F. M. Moghaddam, P.I. Ar-vidsson, Tetrahedron: Asymmetry 2006, 17, 1763;
    • (2006) Tetrahedron: Asymmetry , vol.17 , pp. 1763
    • Govender, T.1    Hojabri, L.2    Moghaddam, F.M.3    Ar-vidsson, P.I.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.