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Volumn 122, Issue 36, 2000, Pages 8640-8647

Are n-BuLi/TMEDA-mediated arene ortholithiations directed? Substituent-dependent rates, substituent-independent mechanisms

Author keywords

[No Author keywords available]

Indexed keywords

HYDROCARBON SUBSTITUENT; LIGAND; LITHIUM DERIVATIVE; POLYCYCLIC AROMATIC HYDROCARBON;

EID: 0034644389     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja001471o     Document Type: Article
Times cited : (107)

References (88)
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    • note
    • 11c under these conditions and the technical difficulties associated with the experiments, we are not quite sure how to interpret these results,
  • 19
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    • (b) For a report describing a 200:1 preference for the n-BuLi/TMEDA-mediated lithiation of anisole relative to benzene, see: Broaddus, C. D. J. Org. Chem. 1970, 55, 10.
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    • note
    • rel in Chart 1 are not statistically weighted compared with those of Schlosser.
  • 38
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    • note
    • The 1:1 statistical ratio is based upon the assumption that precomplexation to either methoxy group affords an equal probability of lithiating at the external or internal positions. In the absence of precomplexation, one would predict a 2:1 probability of external versus internal lithiation.
  • 42
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    • The poor correlation of rates of organolithium reactions with the coordinating power of the donor solvent as well as arguments for why such a correlation should not necessarily exist have been noted previously.29-30
    • The poor correlation of rates of organolithium reactions with the coordinating power of the donor solvent as well as arguments for why such a correlation should not necessarily exist have been noted previously.29-30
  • 43
    • 0001386975 scopus 로고
    • For additional discussions of the role of TMEDA in organolithium chemistry, see: Polyamine-Chelated Alkali Metal Compounds; Langer, A. W., Jr., Ed.; American Chemical Society: Washington, DC, 1974.
    • Collum, D. B. Acc. Chem. Res. 1992, 25, 448. For additional discussions of the role of TMEDA in organolithium chemistry, see: Polyamine-Chelated Alkali Metal Compounds; Langer, A. W., Jr., Ed.; American Chemical Society: Washington, DC, 1974.
    • (1992) Acc. Chem. Res. , vol.25 , pp. 448
    • Collum, D.B.1
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    • For an extensive bibliography on structural studies of n-BuLi/ TMEDA, see ref 29
    • For an extensive bibliography on structural studies of n-BuLi/ TMEDA, see ref 29.
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    • note
    • 6 with NaH in ether followed by alkylation with chloromethyl methylether.
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    • note
    • 27 We tentatively dismiss the rate studies as spurious.
  • 60
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    • note
    • Activation enthalpies calculated according to eq 6 using MNDO suggested that anisole should be less reactive than benzene by 1.4 kcal/ mol. The results for fluorinated anisoles followed more rational trends. Interestingly, another troubling result (subsequently supported by the ab initio studies) was that the reaction of anisole did not favor a discrete LiOMe interaction at all, optimizing to a structure similar to that of 24.
  • 65
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    • Corrections for differences in zero point vibrational and thermal energies were calculated taking into account a scale factor of 0.9804. Wong, M. W. Chem. Phys. Lett. 1996, 250, 391.
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  • 66
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    • A triple ion analogous to 13 was invoked as a possible key intermediate by Shirley; however, it was in the context of a mechanism involving electrophilic aromatic substitution first proposed by Oilman4 that has gone out of favor. Shirley, D. A.; Hendrix, J. P. J. Organomet. Chem. 1968, 77, 217.
    • (1968) J. Organomet. Chem. , vol.77 , pp. 217
    • Shirley, D.A.1    Hendrix, J.P.2
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    • For additional leading references to organolithium open dimers, see: Remenar, J. F.; Lucht, B. L.; Kruglyak, D.; Romesberg, F. E.; Gilchrist, J. H.; Collum, D. B. J. Org. Chem. 1997,62,5748.
    • Nakamura, N.; Nakamura, E.; Koga, N.; Morokuma, K. J. Am. Chem. Soc. 1993,115, 11016. For additional leading references to organolithium open dimers, see: Remenar, J. F.; Lucht, B. L.; Kruglyak, D.; Romesberg, F. E.; Gilchrist, J. H.; Collum, D. B. J. Org. Chem. 1997,62,5748.
    • (1993) J. Am. Chem. Soc. , vol.115 , pp. 11016
    • Nakamura, N.1    Nakamura, E.2    Koga, N.3    Morokuma, K.4
  • 69
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    • note
    • 12,14 comparison of ortholithiation rates with experimentally measured acidities will depend upon whether the acidities stem from (1) solution-phase equilibria or heats of reaction,54 which reflect the stabilities of widely varying and complex aggregate structures of little relationship to transition structures,53 (2) solution-phase kinetic acidities (relative rate constants) for other reactions, which will depend strongly on the choice of solvent, base, and mechanism, (3) gas-phase kinetic acidities,14 which should reflect at least some dependence on the reference base, or (4) experimental gas-phase thermodynamic acidities, which should show no dependence on the reference base.
  • 80
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    • note
    • 2).
  • 81
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    • note
    • The absolute energies for the starting materials and transition structures corrected for zero point vibrational energy differences are reported in the Supporting Information. The activation enthalpies are all calculated relative to the lowest energy conformer. The three conformers of 3 and two conformers of meta-fluoroanisole (19) are of nearly equal stability. Thus, the syn,anti form of 3 is 0.6 kcal/mol more stable than the anti.anti form and 0.5 kcal/mol more stable than the syn.syn form. Similarly, the syn form of 19 is 0.1 kcal/mol more stable than the anti form. These differences are exceedingly small when compared with the relative enthalpies of the syn and anti orientations in the transition structures.
  • 82
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    • note
    • 2 (18). Arene 18 was too fast to measure at -78 °C. Arene 19 lithiated in minutes at -78 °C, while PhF lithiated at least 20 times more slowly.
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    • N,N-Dimethylaniline (20) lithiates very sluggishly when compared to anisole. Slocum, D. W.; Jennings, C. A. J. Org. Chem. 1976, 41, 3653.
    • (1976) J. Org. Chem. , vol.41 , pp. 3653
    • Slocum, D.W.1    Jennings, C.A.2


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.