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Volumn 68, Issue 12, 2003, Pages 4944-4946

Preparation of enantiopure 1-azabicyclo[3.2.2]nonanes Functionalized at carbon C3, from cinchonine and cinchonidine. Stereoselective solvolysis and an easily enolizable ketone

Author keywords

[No Author keywords available]

Indexed keywords

CARBON; DEUTERIUM; SOLVENTS;

EID: 0038616375     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo026890d     Document Type: Article
Times cited : (16)

References (27)
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    • Asymmetric phase transfer reactions
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    • The solvolysis of C9 halogenated quinine and quinidine has been studied in the last century before the advent of modern spectroscopic and separation techniques: (a) Rabe, P. Liebigs Ann. Chem. 1949, 561, 132-158. (b) Rabe, P. Chem. Ber. 1941, 74, 725-728.
    • (1949) Liebigs Ann. Chem. , vol.561 , pp. 132-158
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    • The solvolysis of C9 halogenated quinine and quinidine has been studied in the last century before the advent of modern spectroscopic and separation techniques: (a) Rabe, P. Liebigs Ann. Chem. 1949, 561, 132-158. (b) Rabe, P. Chem. Ber. 1941, 74, 725-728.
    • (1941) Chem. Ber. , vol.74 , pp. 725-728
    • Rabe, P.1
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    • note
    • Replacement of the vinyl group by hydrogen creates enantiomers. The term pseudo-enantiomer is used routinely for related pairs of Cinchona alkaloids, e.g. quinine and quinidine.
  • 13
    • 0038459321 scopus 로고    scopus 로고
    • note
    • The solvolysis of C9 mesylated quinine and quinidine (6′-R = OMe instead of 6′-R = H) was faster than that of 1-OMs and 2-OMs (4-12 h vs 3-4 d for the cinch bases). Cage expansion was less developed (9% for quinine and 36% for quinidine in MeOH). In methanol the products with intact [2.2.2]azabicyclic cage were formed with epimerization at C9 (C9-nat:C9-epi ∼ 1:1). For C9 carbocations derived from quinine and quinidine an open classical cation rather than a nitrogen-bridged species becomes more favorable because of extended conjugation with the 6′-OMe donor ii ↔ iii.
  • 14
    • 0038459320 scopus 로고    scopus 로고
    • note
    • 2 the crude product was purified by column chromatography to furnish 4-OH (82%).
  • 15
    • 0038459319 scopus 로고    scopus 로고
    • note
    • The synthesis of parent 1-azabicyc]o[3.2.2]nonan-3-one (iv) has very recently been put forward as InnoCentive Challenge 260715, $70 000 USD. See www.innocentive.com.
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    • note
    • 1H NMR and NOESY.
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    • Review of kinetic enantioselective protonation of enolates: Fehr, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2566. See also: (b) Zimmerman, H. E.; Wang, P. Org. Lett. 2002, 4, 2593.
    • (1996) Angew. Chem., Int. Ed. Engl. , vol.35 , pp. 2566
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    • Review of kinetic enantioselective protonation of enolates: Fehr, C. Angew. Chem., Int. Ed. Engl. 1996, 35, 2566. See also: (b) Zimmerman, H. E.; Wang, P. Org. Lett. 2002, 4, 2593.
    • (2002) Org. Lett. , vol.4 , pp. 2593
    • Zimmerman, H.E.1    Wang, P.2
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    • note
    • The structure of the nitrogen-bridged intermediate remains open to discussion. While we prefer a flat-topped a-bridged species, a referee has suggested that the limiting case of the highly electrophilic, parent model cation (Q′= H and vinyl group replaced by H) in the gas phase can be described as a conventional aziridinium ion (B3LYP/6-31G* calculations).
  • 20
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    • Cf. also reviews on structural studies of the 2-norbornyl cation: Olah, G. A.; Prakash, G. K. S.; Saunders, M. Acc. Chem. Res. 1983, 16, 440. (b) Methoden der Organischen Chemie, Houben-Weyl; Hanack, M., Ed.; Thieme: Stuttgart, Germany, 1990; Vol. E19c. (c) Saunders, M.; Jiménez-Vazquez, H. A. Chem. Rev. 1991, 91, 375. (d) X-ray crystal structures: Laube, T. Acc. Chem. Res. 1995, 28, 339. (e) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum Press: New York, 1993.
    • (1983) Acc. Chem. Res. , vol.16 , pp. 440
    • Olah, G.A.1    Prakash, G.K.S.2    Saunders, M.3
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    • Hanack, M., Ed.; Thieme: Stuttgart, Germany
    • Cf. also reviews on structural studies of the 2-norbornyl cation: Olah, G. A.; Prakash, G. K. S.; Saunders, M. Acc. Chem. Res. 1983, 16, 440. (b) Methoden der Organischen Chemie, Houben-Weyl; Hanack, M., Ed.; Thieme: Stuttgart, Germany, 1990; Vol. E19c. (c) Saunders, M.; Jiménez-Vazquez, H. A. Chem. Rev. 1991, 91, 375. (d) X-ray crystal structures: Laube, T. Acc. Chem. Res. 1995, 28, 339. (e) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum Press: New York, 1993.
    • (1990) Methoden der Organischen Chemie, Houben-Weyl , vol.E19C
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    • 0002824973 scopus 로고
    • Cf. also reviews on structural studies of the 2-norbornyl cation: Olah, G. A.; Prakash, G. K. S.; Saunders, M. Acc. Chem. Res. 1983, 16, 440. (b) Methoden der Organischen Chemie, Houben-Weyl; Hanack, M., Ed.; Thieme: Stuttgart, Germany, 1990; Vol. E19c. (c) Saunders, M.; Jiménez-Vazquez, H. A. Chem. Rev. 1991, 91, 375. (d) X-ray crystal structures: Laube, T. Acc. Chem. Res. 1995, 28, 339. (e) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum Press: New York, 1993.
    • (1991) Chem. Rev. , vol.91 , pp. 375
    • Saunders, M.1    Jiménez-Vazquez, H.A.2
  • 23
    • 0038120117 scopus 로고
    • Cf. also reviews on structural studies of the 2-norbornyl cation: Olah, G. A.; Prakash, G. K. S.; Saunders, M. Acc. Chem. Res. 1983, 16, 440. (b) Methoden der Organischen Chemie, Houben-Weyl; Hanack, M., Ed.; Thieme: Stuttgart, Germany, 1990; Vol. E19c. (c) Saunders, M.; Jiménez-Vazquez, H. A. Chem. Rev. 1991, 91, 375. (d) X-ray crystal structures: Laube, T. Acc. Chem. Res. 1995, 28, 339. (e) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum Press: New York, 1993.
    • (1995) Acc. Chem. Res. , vol.28 , pp. 339
    • Laube, T.1
  • 24
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    • Plenum Press, New York
    • Cf. also reviews on structural studies of the 2-norbornyl cation: Olah, G. A.; Prakash, G. K. S.; Saunders, M. Acc. Chem. Res. 1983, 16, 440. (b) Methoden der Organischen Chemie, Houben-Weyl; Hanack, M., Ed.; Thieme: Stuttgart, Germany, 1990; Vol. E19c. (c) Saunders, M.; Jiménez-Vazquez, H. A. Chem. Rev. 1991, 91, 375. (d) X-ray crystal structures: Laube, T. Acc. Chem. Res. 1995, 28, 339. (e) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.; Plenum Press: New York, 1993.
    • (1993) Advanced Organic Chemistry, 3rd Ed.
    • Carey, F.A.1    Sundberg, R.J.2


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