Altering the Cyclization Modes: Temperature-Dependent Intramolecular 7-<i>Endo-Dig</i> vs 6-<i>Endo-Dig</i> Electrophilic Ring Closures

In an attempt to construct 10-acyl-5<i>H</i>-benzo­[<i>e</i>]­pyrrolo­[1,2-<i>a</i>]­azepines via acid-catalyzed intramolecular alkyne carbonyl metathesis, two distinctive modes of cyclization were revealed to depend on the reaction temperatures. 5<i>H</i>-Benzo­[<i>e</i>]­pyrrolo­[1,2-<i>a</i>]­azepine-1-carbaldehydes with a substituent at the C11 position were obtained as major products at 90 °C as a result of intramolecular 7-<i>endo-dig</i> cyclization, while 6-<i>endo-dig</i> ring closure by electrophilic addition of nitrogen of the pyrrole to a vinyl cation generated under acidic medium followed by an unprecedented domino rearrangement process was observed at 40 °C in some cases, resulting in 5-aryl-11<i>H</i>-benzo­[<i>d</i>]­pyrrolo­[1,2-<i>a</i>]­azepine-1-carbaldehydes along with the former products

Altering the Cyclization Modes: Temperature-Dependent Intramolecular 7-<i>Endo-Dig</i> vs 6-<i>Endo-Dig</i> Electrophilic Ring Closures

In an attempt to construct 10-acyl-5<i>H</i>-benzo­[<i>e</i>]­pyrrolo­[1,2-<i>a</i>]­azepines via acid-catalyzed intramolecular alkyne carbonyl metathesis, two distinctive modes of cyclization were revealed to depend on the reaction temperatures. 5<i>H</i>-Benzo­[<i>e</i>]­pyrrolo­[1,2-<i>a</i>]­azepine-1-carbaldehydes with a substituent at the C11 position were obtained as major products at 90 °C as a result of intramolecular 7-<i>endo-dig</i> cyclization, while 6-<i>endo-dig</i> ring closure by electrophilic addition of nitrogen of the pyrrole to a vinyl cation generated under acidic medium followed by an unprecedented domino rearrangement process was observed at 40 °C in some cases, resulting in 5-aryl-11<i>H</i>-benzo­[<i>d</i>]­pyrrolo­[1,2-<i>a</i>]­azepine-1-carbaldehydes along with the former products

Local Control of the <i>Cis</i>–<i>Trans</i> Isomerization and Backbone Dihedral Angles in Peptides Using Trifluoromethylated Pseudoprolines

NMR studies and theoretical calculations have been performed on model peptides Ac-Ser­(ΨPro)-NHMe, (<i>S</i>,<i>S</i>)­Ac-Ser­(Ψ^H,CF3Pro)-NHMe, and (<i>R,S</i>)­Ac-Ser­(Ψ^CF3,HPro)-NHMe. Their thermodynamic and kinetic features have been analyzed in chloroform, DMSO, and water, allowing a precise description of their conformational properties. We found that trifluoromethyl C^δ-substitutions of oxazolidine-based pseudoprolines can strongly influence the <i>cis</i>–<i>trans</i> rotational barriers with only moderate effects on the <i>cis</i>/<i>trans</i> population ratio. In CHCl₃, the configuration of the CF₃–C^δ entirely controls the ψ-dihedral angle, allowing the stabilization of γ-turn-like or PPI/PPII-like backbone conformations. Moreover, in water and DMSO, this C^δ-configuration can be used to efficiently constrain the ring puckering without affecting the <i>cis</i>/<i>trans</i> population ratio. Theoretical calculations have ascertained the electronic and geometric properties induced by the trifluoromethyl substituent and provided a rational understanding of the NMR observations