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

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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

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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