Enantioselective Construction of Chiral BispiroOxindole-Pyrrolidine-Pyrazolone Derivatives via Sequential and One-Pot Mannich/Hydroamination Reaction

The atom-economic method for the preparation of novel bispirocyclic compounds containing three fused heterocyclic scaffolds privileged in drug discovery was developed by using a chiral amine-squaramide Mannich reaction and Au(I)-catalyzed hydroamination. The developed synthetic strategy performed either stepwise or as a one-pot process allows the formation of chiral bispirocyclic oxindole-pyrrolidine-pyrazolones in high yields (up to 75%) with excellent enantioselectivities (up to 99%).