5(6)-<i>anti</i>-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, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position

5(6)-<i>anti</i>-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, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position

Selectfluor as a Nucleofuge in the Reactions of Azabicyclo[<i>n</i>.2.1]alkane β-Halocarbamic Acid Esters (<i>n</i> = 2,3)

The ability of Selectfluor to act as a nucleofuge for hydrolysis of β-anti-halides was investigated with N-alkoxycarbonyl derivatives of 6-anti-Y-7-anti-X-2-azabicyclo[2.2.1]heptanes and 4-anti-Y-8-anti-X-6-azabicyclo[3.2.1]octanes. The azabicycles contained X = I or Br groups in the methano bridge and Y = F, Br, Cl, or OH substituents in the larger bridge. The relative reactivities of the halides were a function of the azabicycle, the halide, and its bridge and the addition of Selectfluor or HgF2 as a nucleofuge. All halide displacements occurred with retention of stereochemistry. Selectfluor with sodium bromide or sodium chloride, but not sodium iodide, competitively oxidized some haloalcohols to haloketones. A significant 15.6 Hz F···HO NMR coupling was observed with 4-anti-fluoro-8-anti-hydroxy-6-azabicyclo[3.2.1]octane

5(6)-<i>anti</i>-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, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position

5(6)-<i>anti</i>-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, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position

5(6)-<i>anti</i>-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, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position

Selectfluor as a Nucleofuge in the Reactions of Azabicyclo[<i>n</i>.2.1]alkane β-Halocarbamic Acid Esters (<i>n</i> = 2,3)

The ability of Selectfluor to act as a nucleofuge for hydrolysis of β-anti-halides was investigated with N-alkoxycarbonyl derivatives of 6-anti-Y-7-anti-X-2-azabicyclo[2.2.1]heptanes and 4-anti-Y-8-anti-X-6-azabicyclo[3.2.1]octanes. The azabicycles contained X = I or Br groups in the methano bridge and Y = F, Br, Cl, or OH substituents in the larger bridge. The relative reactivities of the halides were a function of the azabicycle, the halide, and its bridge and the addition of Selectfluor or HgF2 as a nucleofuge. All halide displacements occurred with retention of stereochemistry. Selectfluor with sodium bromide or sodium chloride, but not sodium iodide, competitively oxidized some haloalcohols to haloketones. A significant 15.6 Hz F···HO NMR coupling was observed with 4-anti-fluoro-8-anti-hydroxy-6-azabicyclo[3.2.1]octane

Selectfluor as a Nucleofuge in the Reactions of Azabicyclo[<i>n</i>.2.1]alkane β-Halocarbamic Acid Esters (<i>n</i> = 2,3)

The ability of Selectfluor to act as a nucleofuge for hydrolysis of β-anti-halides was investigated with N-alkoxycarbonyl derivatives of 6-anti-Y-7-anti-X-2-azabicyclo[2.2.1]heptanes and 4-anti-Y-8-anti-X-6-azabicyclo[3.2.1]octanes. The azabicycles contained X = I or Br groups in the methano bridge and Y = F, Br, Cl, or OH substituents in the larger bridge. The relative reactivities of the halides were a function of the azabicycle, the halide, and its bridge and the addition of Selectfluor or HgF2 as a nucleofuge. All halide displacements occurred with retention of stereochemistry. Selectfluor with sodium bromide or sodium chloride, but not sodium iodide, competitively oxidized some haloalcohols to haloketones. A significant 15.6 Hz F···HO NMR coupling was observed with 4-anti-fluoro-8-anti-hydroxy-6-azabicyclo[3.2.1]octane

Neighboring Group Participation in the Additions of Iodonium and Bromonium Ions to <i>N</i>-Alkoxycarbonyl-2-azabicyclo[2.2.<i>n</i>]alk-5-enes (<i>n</i> = 1,2)

Additions of iodonium-X reagents to N-alkoxycarbonyl-2-azabicyclo[2.2.1]hept-5-enes and the homologous 2-azabicyclo[2.2.2]oct-5-enes have been found to mirror the outcomes of additions of bromonium-X reagents. Only rearranged products were observed for reactions of either of these halonium ion reagents with the azabicylo[2.2.1]hept-5-enes. For the azabicyclo[2.2.2]oct-5-enes, nitrogen participation in addition of IOH or BrOH was dependent on the N-alkoxycarbonyl group. With larger N-Boc, N-Cbz, or N-Troc protecting groups, unrearranged 5-anti-hydroxy-6-syn-I(or Br)-2-azabicyclo[2.2.2]octanes were formed by nucleophilic attack at C5 on syn-halonium ions. The structure of N-methyl-8-anti-bromo-4-anti-hydroxy-2-azabicyclo[3.2.1]octane has been reassigned by X-ray analysis

Neighboring Group Participation in the Additions of Iodonium and Bromonium Ions to <i>N</i>-Alkoxycarbonyl-2-azabicyclo[2.2.<i>n</i>]alk-5-enes (<i>n</i> = 1,2)

Additions of iodonium-X reagents to N-alkoxycarbonyl-2-azabicyclo[2.2.1]hept-5-enes and the homologous 2-azabicyclo[2.2.2]oct-5-enes have been found to mirror the outcomes of additions of bromonium-X reagents. Only rearranged products were observed for reactions of either of these halonium ion reagents with the azabicylo[2.2.1]hept-5-enes. For the azabicyclo[2.2.2]oct-5-enes, nitrogen participation in addition of IOH or BrOH was dependent on the N-alkoxycarbonyl group. With larger N-Boc, N-Cbz, or N-Troc protecting groups, unrearranged 5-anti-hydroxy-6-syn-I(or Br)-2-azabicyclo[2.2.2]octanes were formed by nucleophilic attack at C5 on syn-halonium ions. The structure of N-methyl-8-anti-bromo-4-anti-hydroxy-2-azabicyclo[3.2.1]octane has been reassigned by X-ray analysis