Catalytic Enantioselective Construction of Chiral Benzo-Fused N-Heterocycles through Friedel-Crafts-Type Electrophilic Chlorination

Chiral benzo-fused N-heterocycles are frequently found in natural and synthetic products. However, their synthesis usually suffers from different limitations such as difficulty in accessing appropriate starting materials and unsatisfactory stereoselectivities. In this work, an unprecedented chiral sulfide-catalyzed enantioselective Friedel-Crafts-type electrophilic chlorination is shown to construct various 3,4-functionalized tetrahydroquinolines with excellent enantio- and diastereoselectivities from readily available aniline derivatives. Interestingly, employing N-allyl 1-naphthanilides as substrates, divergent reactions via chlorocarbocyclization and dearomatization occurred to afford two chiral polycyclic benzo-fused N-heterocycles. The system that we developed extends the scope of asymmetric chlorination to general substrates without the need of a N-H group, and significantly promotes the synthesis of enantioenriched benzo-fused N-heterocycles. [GRAPHICS] .

Automated summary

In this work, a chiral sulfide-catalyzed electrophilic chlorination reaction was developed for the synthesis of chiral benzo-fused N-heterocycles with excellent enantio- and diastereoselectivities. This method overcomes the limitations of accessing appropriate starting materials and achieving satisfactory stereoselectivities.