Privileged Structures as Peptide Backbone Constraints: Polymer-Supported Stereoselective Synthesis of Benzimidazolinopiperazinone Peptides

A molecular scaffold comprising a privileged structure was designed and synthesized to serve as a peptide backbone conformational constraint. The synthesis of highly functionalized 2,3,10,10<i>a</i>-tetrahydrobenzo­[4,5]­imidazo­[1,2-<i>a</i>]­pyrazin-4­(1<i>H</i>)-ones on a solid-phase support was performed via a tandem <i>N</i>-acyl-<i>N</i>-aryliminium ion cyclization–nucleophilic addition reaction. The synthesis proceeded with full stereocontrol of the newly formed stereogenic center. Conventional and microwave-assisted syntheses were compared with respect to efficiency and the optical integrity of the target compounds. Significant epimerization was observed during acylation with (<i>S</i>)- and (<i>R</i>)-2-bromopropionic acids under microwave conditions.