Enantioselective Construction of Chiral Bispiro[Oxindole-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%).

Automated summary

The atom-economic method developed using a chiral amine-squaramide Mannich reaction and Au(I)-catalyzed hydroamination can efficiently prepare novel bispirocyclic compounds containing three fused heterocyclic scaffolds. This synthetic strategy, whether performed stepwise or as a one-pot process, enables the formation of chiral bispirocyclic [oxindole-pyrrolidine-pyrazolones] with high yields (up to 75%) and excellent enantioselectivities (up to 99%).