Chiral Amine Catalyzed Reductive Aldol/Reductive Michael Addition Cascade Towards Enantioselective Synthesis of Benzannulated Diquinanes

Abstract

AbstractDisclosed here an amine‐catalyzed reductive aldol‐condensation followed by an intramolecular reductive Michael‐addition cascade employing Hantzsch ester as hydride source to a keto‐bis‐enone to provide enantio‐ and diastereoselective benzannulated diquinanes having three consecutive stereocenters, one of which is an all‐carbon quaternary formyl stereocenter. Interestingly, on changing a tether connecting the ketone and an enone moiety from an aliphatic to an aromatic, a change in reactivity is observed. In this case, instead of the above‐mentioned reductive aldol condensation, an asymmetric aldol reaction occurs, followed by an iminium/enamine isomerization and, finally diastereoselective Michael addition reaction occurs. As a result, a bis‐benzannulated diquinane is obtained with vicinal congested quaternary chiral centers.