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

ABSTRACT

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