5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes: A nucleophilic displacement route

Grant R. Krow, Ram Edupuganti, Deepa Gandla, Amit Choudhary, Guoliang Lin, Philip E. Sonnet, Charles DeBrosse, Charles W. Ross, Kevin C. Cannon, Ronald T. Raines

Research output: Contribution to journalArticle

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Abstract

(Chemical Equation Presented) Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y- difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position.

Original languageEnglish (US)
Pages (from-to)8232-8242
Number of pages11
JournalJournal of Organic Chemistry
Volume74
Issue number21
DOIs
StatePublished - Nov 6 2009

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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    Krow, G. R., Edupuganti, R., Gandla, D., Choudhary, A., Lin, G., Sonnet, P. E., DeBrosse, C., Ross, C. W., Cannon, K. C., & Raines, R. T. (2009). 5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes: A nucleophilic displacement route. Journal of Organic Chemistry, 74(21), 8232-8242. https://doi.org/10.1021/jo901725k