Organocatalytic Asymmetric Friedel–Crafts Reaction of Prochiral 3,4-Fused Pyrroles via a Desymmetrization/Kinetic Resolution Sequence

An intriguing but underexplored topic is the central chirality in heteroarene derivatives originating from unsymmetrically substituted heteroarene rings. Herein, we demonstrate the first catalytic enantioselective Friedel-Crafts reaction of prochiral 3,4-fused pyrroles. Allenamides are used as the electrophiles, and an easily available phosphoric acid was employed as the catalyst. Desymmetrization and kinetic resolution, two asymmetric processes, were used successively to produce polycyclic 2-substituted, 3,4-fused pyrroles with high enantioselectivities (up to 98:2 er). Also, the products were elaborated into synthetically challenging chiral isoindole compounds.