Catalytic Enantioselective Desymmetrizing Fischer Indolization through Dynamic Kinetic Resolution

The first catalytic enantioselective Fischer indolization of prochiral diketones containing enantiotopic carbonyl groups is developed and shown to proceed through dynamic kinetic resolution (DKR). Catalyzed by the combination of a spirocyclic chiral phosphoric acid and ZnCl2 (Lewis acid assisted Bronsted acid), this direct approach combines 2,2-disubstituted cyclopentane-1,3-diones with N-protected phenylhydrazines to furnish cyclopenta[b]indole derivatives containing an all-carbon quaternary stereocenter with good to excellent enantioselectivities.

Automated summary

The first catalytic enantioselective Fischer indolization of prochiral diketones containing enantiotopic carbonyl groups is developed through dynamic kinetic resolution. Catalyzed by a combination of a spirocyclic chiral phosphoric acid and ZnCl2, this approach efficiently synthesizes cyclopenta[b]indole derivatives with an all-carbon quaternary stereocenter in good to excellent enantioselectivities.