Highly stereoselective Friedel–Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones based on a stereoselective Friedel–Crafts type cyclization. Cyclization precursors were prepared in two steps, from the readily available (S)-mandelic acid, in 60–80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20–86% yield and with 20–97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.