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

Abstract

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 substrateswithout the need of a N-H group, and significantly promotes the synthesis of enantioenriched benzo-fused N-heterocycles.