Asymmetric Dearomatization of Indoles with Azodicarboxylates via Cascade Electrophilic Amination/Aza-Prins Cyclization/Phenonium-like Rearrangement

Herein, we report a highly efficient synthesis of enantioenrichedaza-[3.3.1]-bicyclic enamines and ketones, a class of structural coresin many natural products, via asymmetric dearomatization of indoleswith azodicarboxylates. The reaction is initiated by electrophilicamination and followed by aza-Prins cyclization/phenonium-like rearrangement.A newly developed fluorine-containing chiral phosphoric acid displaysexcellent activity in promoting this cascade reaction. The absenceor presence of water as the additive directs the reaction pathwaytoward either enamine or ketone products in high yields (up to 93%)with high enantiopurity (up to 98% ee). Comprehensive density functionaltheory (DFT) calculations reveal the energy profile of the reactionand the origins of enantioselectivity and water-induced chemoselectivity.