Enantioselective Mannich Reaction between Cyclic N-Sulfonyl Ketimines and Isatin-Derived Ketimines

J Org Chem. 2024 Sep 20;89(18):13272-13283. doi: 10.1021/acs.joc.4c01405. Epub 2024 Sep 9.

Abstract

An enantioselective Mannich reaction with cyclic N-sulfonyl ketimines as the nucleophiles was developed. In the presence of 5 mol % chiral thiourea catalyst C11, the asymmetric Mannich reaction between cyclic N-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 N-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.