5(6)-anti-Substituted-2-azabicyclo[2.1.1]hexanes: a nucleophilic displacement route.
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, N(3), Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position.
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA. grkrow@temple.edu
Grant R
GR
Krow
Ram
R
Edupuganti
Deepa
D
Gandla
Amit
A
Choudhary
Guoliang
G
Lin
Philip E
PE
Sonnet
Charles
C
DeBrosse
Charles W
CW
Ross
Kevin C
KC
Cannon
Ronald T
RT
Raines
D053961:Azabicyclo Compounds / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006586:Hexanes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D053961:Azabicyclo Compounds; D006586:Hexanes