TY - JOUR
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 C.
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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U2 - 10.1021/jo901725k
DO - 10.1021/jo901725k
M3 - Article
C2 - 19799411
AN - SCOPUS:70350738408
SN - 0022-3263
VL - 74
SP - 8232
EP - 8242
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 21
ER -