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Volumn 26, Issue 24, 2007, Pages 5902-5911

Ruthenium-catalyzed asymmetric electrophilic fluorination of 1,3-dicarbonyl compounds

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSIS; CATALYST SELECTIVITY; CYCLOHEXANE; ENANTIOSELECTIVITY; FLUORINATION; PROTON TRANSFER; STOICHIOMETRY; X RAY ANALYSIS;

EID: 36749101901     PISSN: 02767333     EISSN: None     Source Type: Journal    
DOI: 10.1021/om700714u     Document Type: Article
Times cited : (66)

References (75)
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    • We have previously reported an enantioselectivity of 83% ee for the same reaction.25 In the meantime, we have improved the methods of isolation and purification of 3a. Most probably, trace amounts of impurities were responsible for the lower enantiomeric excess obtained before
    • 25 In the meantime, we have improved the methods of isolation and purification of 3a. Most probably, trace amounts of impurities were responsible for the lower enantiomeric excess obtained before.
  • 58
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    • As a first hypothesis, we attributed this behavior to the formation of a ruthenium(III) complex during the catalytic reaction.25 Attempts to reproduce the original preparation of the alleged enolato complex of ruthenium(III) by chloride abstraction from 1 with (Et 3O)PF6 (2 equiv, followed by oxidation with AgPF 6 (1 equiv or in excess) and addition of 4a (1 equiv or in excess, with or without adding NEt3, always yielded 2a in low purity instead. In addition, we treated the enolato complex 3a with different one-electron oxidants. Although a Ru(III) complex is possibly formed under such conditions, it is reduced back to the ruthenium(II) complex 2a in the presence of a large excess of β-keto ester, which does not support the possibility of Ru(II) → Ru(III) oxidation during catalysis-at least at low substrate conversion
    • 3, always yielded 2a in low purity instead. In addition, we treated the enolato complex 3a with different one-electron oxidants. Although a Ru(III) complex is possibly formed under such conditions, it is reduced back to the ruthenium(II) complex 2a in the presence of a large excess of β-keto ester, which does not support the possibility of Ru(II) → Ru(III) oxidation during catalysis-at least at low substrate conversion.
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    • In CD2Cl2, NHSI is a slightly weaker acid than 2a. The 31P NMR spectrum of a CD2Cl2 solution of 3a and NHSI (1 equiv) shows the signals of 3a exclusively, and the N-H acidic proton gives a broad signal with approximately the expected intensity at δ4.4 in the 1H NMR spectrum. When a 10-fold excess of NHSI is added, the 31P NMR doublets broaden and shift from the position observed for 3a (δ 63.4 and 52.5) to δ 62.8 and 52.2, that is, toward those of 2a (δ 61.2 and 51.3, which we take as an indication that 3a is protonated to a small extent. Upon addition of Et2O CD 2Cl2/Et2O ratio, 7:1, however, the signals return to their original shape, indicating that only 3a is present
    • 2O ratio = 7:1), however, the signals return to their original shape, indicating that only 3a is present.
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    • The structurally closely related ethyl ester 5b was chosen as a model product to allow for the independent determination of the enantiomeric excess of 5a formed in the stoichiometric fluorination of 2a. The use of excess 5a with known ee would have implied calculating the incremental enantiomeric excess, a procedure that amplifies the experimental error.
    • The structurally closely related ethyl ester 5b was chosen as a model product to allow for the independent determination of the enantiomeric excess of 5a formed in the stoichiometric fluorination of 2a. The use of excess 5a with known ee would have implied calculating the incremental enantiomeric excess, a procedure that amplifies the experimental error.
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    • +.
    • +.
  • 64
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    • 2+ (8%). The formation of the latter sets free 4a, which probably deprotonates 2a to 3a.
    • 2+ (8%). The formation of the latter sets free 4a, which probably deprotonates 2a to 3a.
  • 66
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    • A tentative explanation of this fact is that the non-fluorinated β-keto ester 4a is present in part in the enolic form, which is less basic than the keto form. In the fluorinated β-keto ester, the oxygen lone pairs are not delocalized because of the quaternary α-C atom, and this apparently enhances the basicity slightly.
    • A tentative explanation of this fact is that the non-fluorinated β-keto ester 4a is present in part in the enolic form, which is less basic than the keto form. In the fluorinated β-keto ester, the oxygen lone pairs are not delocalized because of the quaternary α-C atom, and this apparently enhances the basicity slightly.
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    • The accumulation of NHSI during catalysis cannot be responsible for this effect, as NHSI does not affect the enantioselectivity of the catalytic reaction (Table 4, run 3).
    • The accumulation of NHSI during catalysis cannot be responsible for this effect, as NHSI does not affect the enantioselectivity of the catalytic reaction (Table 4, run 3).
  • 69
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    • 19F NMR spectra upon addition of excess 5a (10 equiv) to 2a.
    • 19F NMR spectra upon addition of excess 5a (10 equiv) to 2a.
  • 70
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    • We disfavor an alternative explanation based on the presence of different diastereoisomers of 2a or 3a, as their formation is invariably completely diastereoselective.
    • We disfavor an alternative explanation based on the presence of different diastereoisomers of 2a or 3a, as their formation is invariably completely diastereoselective.
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    • Perseghini, M. ETH, Ph.D. Thesis No. 15195, Zurich, Switzerland, 2003.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.