Turning the Imidazole Core into Three-Dimensional Ring Systems: Mild Organocatalytic Entry to Enantiopure 6,7-Dihydrobenzimidazoles

Organocatalytic asymmetric transformation of common aromatic heterocycles via in situ formation of highly reactive dearomatized ortho-quinodimethane diene species and subsequent [4+2] cycloaddition with suitable dienophiles has become a powerful tool to enter cyclohexane-fused heterocycles. Most of these reactions were previously applied to benzo-fused heterocycles or poorly aromatic rings. Herein, we disclose how previously intractable aromatic imidazole rings, equipped with removable methylidene malononitrile activating handle, could be involved as competent cycloaddends with & beta;-aryl enals in efficient eliminative [4+2] cycloadditions under mild organocatalytic conditions. This method allowed the efficient and direct preparation of scantly represented 6,7-dihydrobenzo[d]imidazoles with optimal enantio- and regioselectivities. Post-cycloaddition chemical editing provided imidazole-based ring systems with diverse oxidation state and functional groups.

Automated summary

Organocatalytic asymmetric transformation of aromatic heterocycles via in situ formation of reactive diene species and subsequent cycloaddition has become a powerful tool. This study reveals the efficient and direct preparation of 6,7-dihydrobenzo[d]imidazoles with optimal enantio- and regioselectivities using previously intractable aromatic imidazole rings as cycloaddends. Post-cycloaddition chemical editing allows the modification of imidazole-based ring systems.