메뉴 건너뛰기




Volumn 4, Issue 18, 2002, Pages 3151-3154

Complex-Induced Proximity Effects. Temperature-Dependent Regiochemical Diversity in Lithiation-Electrophilic Substitution Reactions of N-BOC-2-Azabicyclo[2.1.1]hexane. 2,4- and 3,5-Methanoprolines

Author keywords

[No Author keywords available]

Indexed keywords

2,4 METHANOPROLINE; 2,4-METHANOPROLINE; 3,5 METHANOPROLINE; 3,5-METHANOPROLINE; ANTIINFECTIVE AGENT; DRUG DERIVATIVE; FUSED HETEROCYCLIC RINGS; HETEROCYCLIC COMPOUND; LITHIUM DERIVATIVE; NICOTINIC AGENT; PROLINE;

EID: 0037026515     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol026509b     Document Type: Article
Times cited : (33)

References (57)
  • 13
    • 0442268049 scopus 로고    scopus 로고
    • Patent Application WO 98-KR246 19989898
    • Park, T. H.; Ha, Y. H.; Jeong, D. Y. Patent Application WO 98-KR246 19989898; Chem. Abstr. 1999, 130, 182388.
    • Park, T.H.1    Ha, Y.H.2    Jeong, D.Y.3
  • 14
    • 0005699488 scopus 로고    scopus 로고
    • Park, T. H.; Ha, Y. H.; Jeong, D. Y. Patent Application WO 98-KR246 19989898; Chem. Abstr. 1999, 130, 182388.
    • (1999) Chem. Abstr. , vol.130 , pp. 182388
  • 25
    • 0029822037 scopus 로고    scopus 로고
    • Regioselective α-lithiation of a tert-butylformamide at a dibenzylic bridgehead position in preference to a monobenzylic position has been reported. For other examples of related regioselective lithiation-substitution reactions, see: (b) Kopach, M. E.; Meyers, A. I. J. Org. Chem. 1996, 61, 6764.
    • (1996) J. Org. Chem. , vol.61 , pp. 6764
    • Kopach, M.E.1    Meyers, A.I.2
  • 31
    • 0037178349 scopus 로고    scopus 로고
    • For calculated energies and favored geometries of α-lithioamides, see: (b) Wiberg, K. B.; Bailey, W. F. J. Org. Chem. 2002, 67, 5365.
    • (2002) J. Org. Chem. , vol.67 , pp. 5365
    • Wiberg, K.B.1    Bailey, W.F.2
  • 38
    • 0013374665 scopus 로고    scopus 로고
    • For an alternative route to 3-substituted 2-azabicyclo[2.1.1 ]hexanes, see: (a) Krow, G. R.; Yuan, J.; Lin, G.; Sonnet, P. E. Org. Lett. 2002, 4, 1259. (b) Krow, G. R.; Lester, W. S.; Liu, N.; Yuan, J.; Hiller, A.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Cannon, K. J. Org. Chem. 2001, 66, 1811. (c) Krow, G. R.; Lee, Y. B.; Lester, W. S.; Liu, N.; Yuan, J.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Zacharias, D. J. Org. Chem. 2001, 66, 1805.
    • (2002) Org. Lett. , vol.4 , pp. 1259
    • Krow, G.R.1    Yuan, J.2    Lin, G.3    Sonnet, P.E.4
  • 39
    • 0035831145 scopus 로고    scopus 로고
    • For an alternative route to 3-substituted 2-azabicyclo[2.1.1 ]hexanes, see: (a) Krow, G. R.; Yuan, J.; Lin, G.; Sonnet, P. E. Org. Lett. 2002, 4, 1259. (b) Krow, G. R.; Lester, W. S.; Liu, N.; Yuan, J.; Hiller, A.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Cannon, K. J. Org. Chem. 2001, 66, 1811. (c) Krow, G. R.; Lee, Y. B.; Lester, W. S.; Liu, N.; Yuan, J.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Zacharias, D. J. Org. Chem. 2001, 66, 1805.
    • (2001) J. Org. Chem. , vol.66 , pp. 1811
    • Krow, G.R.1    Lester, W.S.2    Liu, N.3    Yuan, J.4    Hiller, A.5    Duo, J.6    Herzon, S.B.7    Nguyen, Y.8    Cannon, K.9
  • 40
    • 0035831229 scopus 로고    scopus 로고
    • For an alternative route to 3-substituted 2-azabicyclo[2.1.1 ]hexanes, see: (a) Krow, G. R.; Yuan, J.; Lin, G.; Sonnet, P. E. Org. Lett. 2002, 4, 1259. (b) Krow, G. R.; Lester, W. S.; Liu, N.; Yuan, J.; Hiller, A.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Cannon, K. J. Org. Chem. 2001, 66, 1811. (c) Krow, G. R.; Lee, Y. B.; Lester, W. S.; Liu, N.; Yuan, J.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Zacharias, D. J. Org. Chem. 2001, 66, 1805.
    • (2001) J. Org. Chem. , vol.66 , pp. 1805
    • Krow, G.R.1    Lee, Y.B.2    Lester, W.S.3    Liu, N.4    Yuan, J.5    Duo, J.6    Herzon, S.B.7    Nguyen, Y.8    Zacharias, D.9
  • 42
  • 45
    • 0442263431 scopus 로고    scopus 로고
    • note
    • 2 afforded only bridgehead acid 8a (49%). Traces of water may have selectively quenched the 3-anion 5.
  • 49
    • 0442263434 scopus 로고    scopus 로고
    • note
    • 2, gave erratic results. In one trial at -78 °C with sec-BuLi (1.6 equiv), azabicycle 4 afforded only aldehyde 8c (31%). In another trial, a 15:85 mixture of aldehydes 6c/8c (57%) was observed. Under the same conditions except with less base (1.05-1.10 equiv), there were numerous failures to observe any reaction; one trial gave unreacted 4/6c/8c = 67:0:33 (23%). These results may reflect selective quenching of the less stable 3-anion 5 with a proton source (water, dimethylamine?). In a trial in which reaction was allowed to continue overnight rather than 2 h, the 3-isomer was found to predominate: 6c/8c = 97:3 (41%). This result is consistent with the preferential loss of bridgehead aldehyde 8c noted during purification.
  • 50
    • 0442264987 scopus 로고    scopus 로고
    • note
    • 3 exchange was observed in either case.
  • 51
    • 0000920450 scopus 로고
    • Restricted rotation about the C-N bond of N-BOC pyrrolidine was presumed at -78 °C
    • (a) Beak, P.; Kerrick, S. T.; Wu, S.; Chu, J. J. Am. Chem. Soc. 1994, 116, 3231. Restricted rotation about the C-N bond of N-BOC pyrrolidine was presumed at -78 °C.
    • (1994) J. Am. Chem. Soc. , vol.116 , pp. 3231
    • Beak, P.1    Kerrick, S.T.2    Wu, S.3    Chu, J.4
  • 52
    • 0009709215 scopus 로고
    • An N-COOMe rotational barrier of 16 kcal/mol was determined at -3 °C
    • (b) Price, B. J.; Smallman, R. V.; Sutherland, I. O. Chem. Commun. 1966, 319. An N-COOMe rotational barrier of 16 kcal/mol was determined at -3 °C.
    • (1966) Chem. Commun. , pp. 319
    • Price, B.J.1    Smallman, R.V.2    Sutherland, I.O.3
  • 53
    • 0028238053 scopus 로고
    • See ref 27 therein in comparing carbamates to amides: "few amides have rotational barriers of less than 15 kcal/mol and coordination of the carbonyl raises the barrier."
    • (c) Gawley, R. E.; Zhang, Q. Tetrahedron 1994, 50, 6077. See ref 27 therein in comparing carbamates to amides: "few amides have rotational barriers of less than 15 kcal/mol and coordination of the carbonyl raises the barrier."
    • (1994) Tetrahedron , vol.50 , pp. 6077
    • Gawley, R.E.1    Zhang, Q.2
  • 55
    • 0442263433 scopus 로고    scopus 로고
    • note
    • 16c are somewhat pyramidal.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.