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Volumn 131, Issue 31, 2009, Pages 10872-10874

Catalytic asymmetric intermolecular stetter reaction of heterocyclic aldehydes with nitroalkenes: Backbone fluorination improves selectivity

Author keywords

[No Author keywords available]

Indexed keywords

CATALYST STRUCTURES; CHEMICAL EQUATIONS; FLUORINE SUBSTITUENTS; FLUORINE SUBSTITUTION; HETEROCYCLIC ALDEHYDE; N-HETEROCYCLIC CARBENES; NITROALKENES; PRECATALYSTS; STEREOELECTRONIC EFFECT; STETTER REACTION; X RAY STRUCTURE ANALYSIS;

EID: 68249139769     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja904375q     Document Type: Article
Times cited : (209)

References (35)
  • 7
  • 10
    • 22144480983 scopus 로고    scopus 로고
    • For the syntheses of triazolium salts, see
    • For the syntheses of triazolium salts, see: Kerr, M. S.; Read de Alaniz, J.; Rovis, T. J. Org. Chem. 2005, 70, 5725-5728.
    • (2005) J. Org. Chem , vol.70 , pp. 5725-5728
    • Kerr, M.S.1    Read de Alaniz, J.2    Rovis, T.3
  • 21
    • 33646146207 scopus 로고    scopus 로고
    • Scheidt has reported a single example of the asymmetric conjugate addition of a stoichiometrically generated acyl anion equivalent to nitroalkenes mediated by a thiourea; see: Mattson, A. E, Zuhl, A. M, Reynolds, T. E, Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4932-4933
    • Scheidt has reported a single example of the asymmetric conjugate addition of a stoichiometrically generated acyl anion equivalent to nitroalkenes mediated by a thiourea; see: Mattson, A. E.; Zuhl, A. M.; Reynolds, T. E.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4932-4933.
  • 23
    • 68249159091 scopus 로고    scopus 로고
    • Other solvents: PhMe (trace), THF (trace), EtOH (59%, 70% ee).
    • Other solvents: PhMe (trace), THF (trace), EtOH (59%, 70% ee).
  • 25
    • 28044458136 scopus 로고    scopus 로고
    • 2-symmetric difluoro-pyrrolidine derivative has been shown to be a moderately effective ligand in the asymmetric epoxidation of an allylic alcohol: Marson, C. M.; Melling, R. C. J. Org. Chem. 2005, 70, 9771-9779.
    • 2-symmetric difluoro-pyrrolidine derivative has been shown to be a moderately effective ligand in the asymmetric epoxidation of an allylic alcohol: Marson, C. M.; Melling, R. C. J. Org. Chem. 2005, 70, 9771-9779.
  • 26
    • 44349084146 scopus 로고    scopus 로고
    • 4-Fluoroproline has been demonstrated to provide improved selectivities in transannular aldols. Chandler, C. L.; List, B. J. Am. Chem. Soc. 2008, 130, 6737-6739.
    • (b) 4-Fluoroproline has been demonstrated to provide improved selectivities in transannular aldols. Chandler, C. L.; List, B. J. Am. Chem. Soc. 2008, 130, 6737-6739.
  • 27
    • 70349783652 scopus 로고    scopus 로고
    • It has recently been argued that a fluorine substituent improves iminium ion geometry in asymmetric epoxidation of unsaturated aldehydes. Sparr, C, Schweizer, W. B, Senn, H. M, Gilmour, R. Angew. Chem, Int. Ed. 2009, 48, 3065-3068
    • (c) It has recently been argued that a fluorine substituent improves iminium ion geometry in asymmetric epoxidation of unsaturated aldehydes. Sparr, C.; Schweizer, W. B.; Senn, H. M.; Gilmour, R. Angew. Chem., Int. Ed. 2009, 48, 3065-3068.
  • 28
    • 68249137793 scopus 로고    scopus 로고
    • We are aware of the caveats associated with solid-state analysis of a precatalyst; however, these arguments are self-consistent and rationalize the observed results
    • We are aware of the caveats associated with solid-state analysis of a precatalyst; however, these arguments are self-consistent and rationalize the observed results.
  • 31
    • 68249152895 scopus 로고    scopus 로고
    • Another hyperconjugative effect that cannot be ruled out is a π to σ*C-F interaction. Schaefer et al. reported that fluorine in benzyl fluorides adopts a perpendicular arrangement with respect to the aromatic ring, due to π donation of the aromatic ring into the low lying σ*C-F. A similar effect can be rationalized for our system where hyperconjugation can only occur from the observed Cγ-exo ring pucker. We believe this is unlikely due to the developing positive charge in the azolium ring occurring in the transition state of the C-C bond-forming event but may play a small role. See: Schaefer, T, Schurko, R. W, Sebastian, R, Hruska, F. E. Can. J. Chem. 1995, 73, 816-825
    • C-F. A similar effect can be rationalized for our system where hyperconjugation can only occur from the observed Cγ-exo ring pucker. We believe this is unlikely due to the developing positive charge in the azolium ring occurring in the transition state of the C-C bond-forming event but may play a small role. See: Schaefer, T.; Schurko, R. W.; Sebastian, R.; Hruska, F. E. Can. J. Chem. 1995, 73, 816-825.
  • 32
    • 68249139362 scopus 로고    scopus 로고
    • Benzaldehyde fails to participate under these conditions. The reasons for this are the subject of investigation in our laboratory. Evidence suggests that the role of the heteroatom is not simply that of a proximal Lewis base given that both pyridazine carboxaldehyde and furfural participate with equal facility in spite of their very low basicity
    • Benzaldehyde fails to participate under these conditions. The reasons for this are the subject of investigation in our laboratory. Evidence suggests that the role of the heteroatom is not simply that of a proximal Lewis base given that both pyridazine carboxaldehyde and furfural participate with equal facility in spite of their very low basicity.
  • 33
    • 68249160253 scopus 로고    scopus 로고
    • Numerical comparison of ee values is problematic. Comparison of er values can be equally problematic. For example, 3d is formed in 98:2 er with 8 and 93:7 er with 6, an apparent difference of 5 er points. However, a more instructive comparison here would be 13:1 vs 49:1 for 3d.
    • Numerical comparison of ee values is problematic. Comparison of er values can be equally problematic. For example, 3d is formed in 98:2 er with 8 and 93:7 er with 6, an apparent difference of 5 er points. However, a more instructive comparison here would be 13:1 vs 49:1 for 3d.


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