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

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.