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Volumn 71, Issue 4, 2006, Pages 1430-1435

C-metalated nitriles: Electrophile-dependent alkylations and acylations

Author keywords

[No Author keywords available]

Indexed keywords

CARBONYL ADDITION-CONJUGATE ADDITION; ELECTROPHILE; GRIGNARD REAGENTS; MAGNESIATED NITRILES;

EID: 33644517212     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo052102j     Document Type: Article
Times cited : (29)

References (88)
  • 13
    • 0000609569 scopus 로고
    • The sole exception is a structurally biased lithiated cyclopropanecarbonitrile, where N and C coordination occur in a polymeric ladder structure: Boche, G.; Harms, K.; Marsch, M. J. Am. Chem. Soc. 1988, 110, 6925.
    • (1988) J. Am. Chem. Soc. , vol.110 , pp. 6925
    • Boche, G.1    Harms, K.2    Marsch, M.3
  • 49
    • 0003961355 scopus 로고    scopus 로고
    • Pergamon: Amsterdam, The Netherlands; Chapter 6
    • For an excellent discussion of electrophile-dependent alkylations of chiral organolithiums, see: Clayden, J. Organolithiums: Selectivity for Synthesis; Pergamon: Amsterdam, The Netherlands, 2002; Chapter 6.
    • (2002) Organolithiums: Selectivity for Synthesis
    • Clayden, J.1
  • 58
    • 33644501627 scopus 로고    scopus 로고
    • note
    • Cyclic nitrile 9a can be prepared through the conjugate addition of MeMgCl to 3-hydroxy-3-methylcyclohex-1-enecarbonitrile or more conveniently, by sequential 1,2-1,4 addition to oxonitrile 14 (vide infra).
  • 62
    • 33644513564 scopus 로고    scopus 로고
    • note
    • 1H NMR analysis of the crude reaction mixture failed to identify any of the diastereomer 9b.
  • 66
    • 85080848774 scopus 로고    scopus 로고
    • Electrophile-dependent alkylations are relatively rare but often occur with chiral, tertiary, benzylic and allylic organolithiums. Collectively, the occurrence of electrophile-dependent stereoselectivity implies the intermediacy of a chiral organometallic intermediate, in this case, the asymmetric C-magnesiated nitrile 11. (a) Basu, A.; Thayumanavan, S. Angew. Chem., Int. Ed. 2002, 41, 717.
    • (2002) Angew. Chem., Int. Ed. , vol.41 , pp. 717
    • Basu, A.1    Thayumanavan, S.2
  • 67
    • 33644560805 scopus 로고    scopus 로고
    • Wiley: New York: Chapter 1
    • The Mg-O bond exhibits considerable back-bonding, which dramatically reduces the Lewis acidity of the metal, making prior coordination with the electrophile unlikely: Richey, H. G. Grignard Reagents: New Developments; Wiley: New York, 2000: Chapter 1. p 4.
    • (2000) Grignard Reagents: New Developments , pp. 4
    • Richey, H.G.1
  • 70
    • 0011316776 scopus 로고
    • For an excellent discussion of the mechanism of these formally forbidden alkylations, see: Hill, E. A. J. Organomet. Chem. 1975, 91, 123.
    • (1975) J. Organomet. Chem. , vol.91 , pp. 123
    • Hill, E.A.1
  • 71
    • 33644510614 scopus 로고    scopus 로고
    • note
    • The attempted oxidation of 9k afforded the cyclic ether 9o, presumably by the ionization of an activated cyclopropyl alcohol, followed by an internal cyclization, as shown below.
  • 74
    • 0033522843 scopus 로고    scopus 로고
    • For an excellent overview of terms, steric constraints, and orbital overlap, see: Gawley, R. E. Tetrahedron Lett. 1999, 40, 4297.
    • (1999) Tetrahedron Lett. , vol.40 , pp. 4297
    • Gawley, R.E.1
  • 75
    • 33644556308 scopus 로고    scopus 로고
    • note
    • An analogous alkylation of 11a with 4-bromobutene similarly affords only 22% of the corresponding alkylated nitriles 9r and 13r, with the protonated nitriles 9a and 13a predominating. (diagram presented)
  • 76
    • 33644509067 scopus 로고    scopus 로고
    • note
    • inv) attack (cf. 11a′).
  • 80
    • 33644520116 scopus 로고    scopus 로고
    • Richey, H. G., Jr., Ed.; Wiley: Chichester, England, Chapter 1
    • For SET reactions of Grignard reagents, see: (d) Hill, E. A. In Grignard Reagents: New Developments; Richey, H. G., Jr., Ed.; Wiley: Chichester, England, 2000; Chapter 1, pp 43-45.
    • (2000) Grignard Reagents: New Developments , pp. 43-45
    • Hill, E.A.1
  • 81
    • 33644537833 scopus 로고    scopus 로고
    • note
    • No alkylation of 11a is observed with the less reactive, but commercially available, cyclopropylmethyl bromide.
  • 84
    • 33644520730 scopus 로고    scopus 로고
    • note
    • 18 the use of low titre MeMgCl afforded almost exclusively the cyclopropylnitriles 9q and 13q (53%) and only a trace amount of the butenylnitriles 9r and 13r. Presumably, the presence of alkoxide species causes a change in the nature of the reactive magnesiated nitrile, which has minimal propensity toward SET.
  • 85
    • 33644502369 scopus 로고    scopus 로고
    • note
    • No alkylation was observed between 11a and DMF, methyl benzoate, or dimethyl carbonate.
  • 86
    • 0000526031 scopus 로고    scopus 로고
    • Control experiments, in which the temperature was raised to room temperature, cause equilibration of the intermediate alkoxy nitrile, whereas quenching the reaction at -78 °C retains the stereochemical integrity of the first-formed alkoxy nitriles: Carlier, P. R.; Lo, C. W.-S.; Lo, M. M.-C.; Wan, N. C.; Williams, I. D. Org. Lett. 2000, 2, 2443. For example, in the alkylation of 11a with cyclopropanecarboxaldehyde, elevating the reaction to ambient temperature causes an equilibration to a mixture of nitriles 9k and 13k and two diastereomeric lactones, iii. Presumably, higher temperatures facilitate not only retro-aldol fragmentation but also attack of the adjacent magnesium alkoxide onto the nitrile to generate ii, which hydrolyzes to iii. (diagram presented)
    • (2000) Org. Lett. , vol.2 , pp. 2443
    • Carlier, P.R.1    Lo, C.W.-S.2    Lo, M.M.-C.3    Wan, N.C.4    Williams, I.D.5


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.