Conformational Switching of 3,7-Diacyl-3,7-diazabicyclo[3.3.1]nonanes by Metal Binding and by Solvent Changes

Abstract

3,7‐Diacyl‐3,7‐diazabicyclo[3.3.1]nonanes (3,7‐diacylbispidines) can switch from antiparallel to parallel conformations upon addition of LaCl3 thus serving as models for potential allosteric systems.

Bispidine as a β-strand nucleator: from a β-arch to self-assembled cages and vesicles

“…20 In CDCl3, the ratio of anti to syn was 3:1, while DMSO favored the structure with high dipole moment, the syn conformer. 24,25 ROESY spectrum confirmed the presence of syn and anticonformers in F3 (Fig. 3a, b).…”

Bispidine as a β-strand nucleator: from a β-arch to self-assembled cages and vesicles

“…20 In CDCl3, the ratio of anti to syn was 3:1, while DMSO favored the structure with high dipole moment, the syn conformer. 24,25 ROESY spectrum confirmed the presence of syn and anticonformers in F3 (Fig. 3a, b).…”

Conformational Study of N,N′-Diacyl Bispidines and Dioxo Bis-bispidines: Planar Chirality and Molecular Switching

“… Most of the stereochemical studies have focused on the bicyclic structure, which may adopt a chair–boat or chair–chair conformation depending on the substituents, particularly at the C9, N3, and N7 positions (Figure ). , Furthermore, it has been reported that adding lanthanide agents to N , N ′-diacetyl bispidine 1 (R = COMe, R′ = Me) can induce significant conformational switching with respect to the amide groups . In 2008, planar chirality was observed in bispidinones 2 (R = COMe, R′ = Ph) by Albeck and co-workers through NMR studies .…”

“…15,16 This yields an enthalpy (ΔH ‡ ) and entropy (ΔS ‡ ) of activation of 14 kcal/mol and −10 cal mol −1 K −1 , respectively, with a free energy of activation (ΔG ‡ 298 ) of 17 kcal/mol. 15 The latter is comparable to the rotation barrier in various amides (ΔG ‡ = 15−20 kcal/mol) 16 and close to that in N,N′-diacetyl bispidine 1 (R = COMe, R′ = Me, ΔG ‡ 298 = 18 kcal/mol), 5 suggesting that the two amide rotations are likely independent of each other and that substituents at the bridgeheads do not have discernible impact on the amide rotation dynamics. The rotation barrier also indicates that resolution of the enantiomers would be infeasible under ambient conditions.…”

“…In addition, the value of 0.31 is 50% higher than the largest [syn]/[anti] ratio of 0.20 previously observed for a bispidine compound in DMSO-d 6 (1, R = COMe, R′ = Me). 5 This indicates that the bridgehead substituents can affect the [syn]/[anti] ratio considerably and that, in their absence, syn-4c is stabilized more by DMSO due in part to less steric interference in the solute−solvent dipolar interactions.…”

“…For 4c , it increases from 0.06 in chloroform- d to 0.31 in DMSO- d 6 , probably as a result of stronger dipole–dipole interactions between the polar syn isomer and DMSO (Table , Figure ). In addition, the value of 0.31 is 50% higher than the largest [ syn ]/[ anti ] ratio of 0.20 previously observed for a bispidine compound in DMSO- d 6 ( 1 , R = COMe, R′ = Me) . This indicates that the bridgehead substituents can affect the [ syn ]/[ anti ] ratio considerably and that, in their absence, syn - 4c is stabilized more by DMSO due in part to less steric interference in the solute–solvent dipolar interactions.…”

Bispidine as a β-strand nucleator: from a β-arch to self-assembled cages and vesicles

“…20 In CDCl3, the ratio of anti to syn was 3:1, while DMSO favored the structure with high dipole moment, the syn conformer. 24,25 ROESY spectrum confirmed the presence of syn and anticonformers in F3 (Fig. 3a, b).…”

Conformational Study of N,N′-Diacyl Bispidines and Dioxo Bis-bispidines: Planar Chirality and Molecular Switching

“… Most of the stereochemical studies have focused on the bicyclic structure, which may adopt a chair–boat or chair–chair conformation depending on the substituents, particularly at the C9, N3, and N7 positions (Figure ). , Furthermore, it has been reported that adding lanthanide agents to N , N ′-diacetyl bispidine 1 (R = COMe, R′ = Me) can induce significant conformational switching with respect to the amide groups . In 2008, planar chirality was observed in bispidinones 2 (R = COMe, R′ = Ph) by Albeck and co-workers through NMR studies .…”

“…15,16 This yields an enthalpy (ΔH ‡ ) and entropy (ΔS ‡ ) of activation of 14 kcal/mol and −10 cal mol −1 K −1 , respectively, with a free energy of activation (ΔG ‡ 298 ) of 17 kcal/mol. 15 The latter is comparable to the rotation barrier in various amides (ΔG ‡ = 15−20 kcal/mol) 16 and close to that in N,N′-diacetyl bispidine 1 (R = COMe, R′ = Me, ΔG ‡ 298 = 18 kcal/mol), 5 suggesting that the two amide rotations are likely independent of each other and that substituents at the bridgeheads do not have discernible impact on the amide rotation dynamics. The rotation barrier also indicates that resolution of the enantiomers would be infeasible under ambient conditions.…”

“…In addition, the value of 0.31 is 50% higher than the largest [syn]/[anti] ratio of 0.20 previously observed for a bispidine compound in DMSO-d 6 (1, R = COMe, R′ = Me). 5 This indicates that the bridgehead substituents can affect the [syn]/[anti] ratio considerably and that, in their absence, syn-4c is stabilized more by DMSO due in part to less steric interference in the solute−solvent dipolar interactions.…”

“…For 4c , it increases from 0.06 in chloroform- d to 0.31 in DMSO- d 6 , probably as a result of stronger dipole–dipole interactions between the polar syn isomer and DMSO (Table , Figure ). In addition, the value of 0.31 is 50% higher than the largest [ syn ]/[ anti ] ratio of 0.20 previously observed for a bispidine compound in DMSO- d 6 ( 1 , R = COMe, R′ = Me) . This indicates that the bridgehead substituents can affect the [ syn ]/[ anti ] ratio considerably and that, in their absence, syn - 4c is stabilized more by DMSO due in part to less steric interference in the solute–solvent dipolar interactions.…”

Bispidine as a β-strand nucleator: from a β-arch to self-assembled cages and vesicles

“…20 In CDCl3, the ratio of anti to syn was 3:1, while DMSO favored the structure with high dipole moment, the syn conformer. 24,25 ROESY spectrum confirmed the presence of syn and anticonformers in F3 (Fig. 3a, b).…”

Conformational Study of N,N′-Diacyl Bispidines and Dioxo Bis-bispidines: Planar Chirality and Molecular Switching

“… Most of the stereochemical studies have focused on the bicyclic structure, which may adopt a chair–boat or chair–chair conformation depending on the substituents, particularly at the C9, N3, and N7 positions (Figure ). , Furthermore, it has been reported that adding lanthanide agents to N , N ′-diacetyl bispidine 1 (R = COMe, R′ = Me) can induce significant conformational switching with respect to the amide groups . In 2008, planar chirality was observed in bispidinones 2 (R = COMe, R′ = Ph) by Albeck and co-workers through NMR studies .…”

“…15,16 This yields an enthalpy (ΔH ‡ ) and entropy (ΔS ‡ ) of activation of 14 kcal/mol and −10 cal mol −1 K −1 , respectively, with a free energy of activation (ΔG ‡ 298 ) of 17 kcal/mol. 15 The latter is comparable to the rotation barrier in various amides (ΔG ‡ = 15−20 kcal/mol) 16 and close to that in N,N′-diacetyl bispidine 1 (R = COMe, R′ = Me, ΔG ‡ 298 = 18 kcal/mol), 5 suggesting that the two amide rotations are likely independent of each other and that substituents at the bridgeheads do not have discernible impact on the amide rotation dynamics. The rotation barrier also indicates that resolution of the enantiomers would be infeasible under ambient conditions.…”

“…In addition, the value of 0.31 is 50% higher than the largest [syn]/[anti] ratio of 0.20 previously observed for a bispidine compound in DMSO-d 6 (1, R = COMe, R′ = Me). 5 This indicates that the bridgehead substituents can affect the [syn]/[anti] ratio considerably and that, in their absence, syn-4c is stabilized more by DMSO due in part to less steric interference in the solute−solvent dipolar interactions.…”

“…For 4c , it increases from 0.06 in chloroform- d to 0.31 in DMSO- d 6 , probably as a result of stronger dipole–dipole interactions between the polar syn isomer and DMSO (Table , Figure ). In addition, the value of 0.31 is 50% higher than the largest [ syn ]/[ anti ] ratio of 0.20 previously observed for a bispidine compound in DMSO- d 6 ( 1 , R = COMe, R′ = Me) . This indicates that the bridgehead substituents can affect the [ syn ]/[ anti ] ratio considerably and that, in their absence, syn - 4c is stabilized more by DMSO due in part to less steric interference in the solute–solvent dipolar interactions.…”