Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols

G. R. Krow, W. S. Lester, N. Liu, J. Yuan, A. Hiller, J. Duo, S. B. Herzon, Y. Nguyen, Kevin Charles Cannon

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endohydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo-[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo-[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo-[2.1.1]-hexan-5-ols 15a,b and 15d-g.

Original languageEnglish (US)
Pages (from-to)1811-1817
Number of pages7
JournalJournal of Organic Chemistry
Volume66
Issue number5
DOIs
StatePublished - Mar 9 2001

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Hexanols
Alkenes
Hexanes
Epoxy Compounds
Bromine
Dimethyl Sulfoxide
Isomers
bromohydrins

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Krow, G. R., Lester, W. S., Liu, N., Yuan, J., Hiller, A., Duo, J., ... Cannon, K. C. (2001). Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols. Journal of Organic Chemistry, 66(5), 1811-1817. https://doi.org/10.1021/jo001558s
Krow, G. R. ; Lester, W. S. ; Liu, N. ; Yuan, J. ; Hiller, A. ; Duo, J. ; Herzon, S. B. ; Nguyen, Y. ; Cannon, Kevin Charles. / Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols. In: Journal of Organic Chemistry. 2001 ; Vol. 66, No. 5. pp. 1811-1817.
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title = "Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols",
abstract = "Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endohydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo-[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo-[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo-[2.1.1]-hexan-5-ols 15a,b and 15d-g.",
author = "Krow, {G. R.} and Lester, {W. S.} and N. Liu and J. Yuan and A. Hiller and J. Duo and Herzon, {S. B.} and Y. Nguyen and Cannon, {Kevin Charles}",
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Krow, GR, Lester, WS, Liu, N, Yuan, J, Hiller, A, Duo, J, Herzon, SB, Nguyen, Y & Cannon, KC 2001, 'Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols', Journal of Organic Chemistry, vol. 66, no. 5, pp. 1811-1817. https://doi.org/10.1021/jo001558s

Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols. / Krow, G. R.; Lester, W. S.; Liu, N.; Yuan, J.; Hiller, A.; Duo, J.; Herzon, S. B.; Nguyen, Y.; Cannon, Kevin Charles.

In: Journal of Organic Chemistry, Vol. 66, No. 5, 09.03.2001, p. 1811-1817.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols

AU - Krow, G. R.

AU - Lester, W. S.

AU - Liu, N.

AU - Yuan, J.

AU - Hiller, A.

AU - Duo, J.

AU - Herzon, S. B.

AU - Nguyen, Y.

AU - Cannon, Kevin Charles

PY - 2001/3/9

Y1 - 2001/3/9

N2 - Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endohydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo-[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo-[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo-[2.1.1]-hexan-5-ols 15a,b and 15d-g.

AB - Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endohydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo-[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo-[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo-[2.1.1]-hexan-5-ols 15a,b and 15d-g.

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Krow GR, Lester WS, Liu N, Yuan J, Hiller A, Duo J et al. Synthesis of novel 2-azabicyclo[2.2.0]- and [2.1.1]hexanols. Journal of Organic Chemistry. 2001 Mar 9;66(5):1811-1817. https://doi.org/10.1021/jo001558s