Enantioselective Mannich Reaction between Cyclic <i>N</i>-Sulfonyl Ketimines and Isatin-Derived Ketimines

An enantioselective Mannich reaction with cyclic <i>N</i>-sulfonyl ketimines as the nucleophiles was developed. In the presence of 5 mol % chiral thiourea catalyst <b>C11</b>, the asymmetric Mannich reaction between cyclic <i>N</i>-sulfonyl ketimines and isatin-derived ketimines was achieved in high yields and good-to-excellent enantioselectivities (84-99% yields with 75-99.8% ee). This methodology provided an effective route to construct chiral 3-amino-2-oxindoles containing a cyclic <i>N</i>-sulfonyl ketimine scaffold. The initial biological evaluation of the products in cell-based assays demonstrated that some compounds have excellent antiproliferative activity against human osteosarcoma cells.