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 Charles Cannon, Ronald T. Raines

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

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Hexanes
Bromides
Salts
Dimethyl Sulfoxide
Fluorides
Lithium
Reaction rates
Amines
Substitution reactions
Nitrogen
Metals
Sodium
Ions
Electrons
imidazole
nitromethane
silver fluoride

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

Krow, G. R., Edupuganti, R., Gandla, D., Choudhary, A., Lin, G., Sonnet, P. E., ... 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
Krow, Grant R. ; Edupuganti, Ram ; Gandla, Deepa ; Choudhary, Amit ; Lin, Guoliang ; Sonnet, Philip E. ; DeBrosse, Charles ; Ross, Charles W. ; Cannon, Kevin Charles ; Raines, Ronald T. / 5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes : A nucleophilic displacement route. In: Journal of Organic Chemistry. 2009 ; Vol. 74, No. 21. pp. 8232-8242.
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Krow, GR, Edupuganti, R, Gandla, D, Choudhary, A, Lin, G, Sonnet, PE, DeBrosse, C, Ross, CW, Cannon, KC & Raines, RT 2009, '5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes: A nucleophilic displacement route', Journal of Organic Chemistry, vol. 74, no. 21, pp. 8232-8242. https://doi.org/10.1021/jo901725k

5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes : A nucleophilic displacement route. / Krow, Grant R.; Edupuganti, Ram; Gandla, Deepa; Choudhary, Amit; Lin, Guoliang; Sonnet, Philip E.; DeBrosse, Charles; Ross, Charles W.; Cannon, Kevin Charles; Raines, Ronald T.

In: Journal of Organic Chemistry, Vol. 74, No. 21, 06.11.2009, p. 8232-8242.

Research output: Contribution to journalArticle

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T1 - 5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes

T2 - A nucleophilic displacement route

AU - Krow, Grant R.

AU - Edupuganti, Ram

AU - Gandla, Deepa

AU - Choudhary, Amit

AU - Lin, Guoliang

AU - Sonnet, Philip E.

AU - DeBrosse, Charles

AU - Ross, Charles W.

AU - Cannon, Kevin Charles

AU - Raines, Ronald T.

PY - 2009/11/6

Y1 - 2009/11/6

N2 - (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.

AB - (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.

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Krow GR, Edupuganti R, Gandla D, Choudhary A, Lin G, Sonnet PE et al. 5(6)-anti-substituted-2-azabicyclo[2.1.1]hexanes: A nucleophilic displacement route. Journal of Organic Chemistry. 2009 Nov 6;74(21):8232-8242. https://doi.org/10.1021/jo901725k