Copper(II)-Catalyzed Enantioselective Addition of Aryl Amines to Isatin-Derived N-Boc-Ketimines for the Synthesis of Acyclic N, N'-Ketals

J Org Chem. 2024 Dec 31. doi: 10.1021/acs.joc.4c01794. Online ahead of print.

Abstract

Here, we demonstrated a copper(II)-catalyzed enantioselective addition of aryl amines to isatin-derived N-Boc-ketimines using chiral O-N-N tridentate ligands derived from BINOL and proline. Generally, the chiral acyclic N,N'-ketals were obtained in high yields (up to 98%) and excellent ee values (up to 98%). Various aryl amines could be tolerated and a gram-scale reaction was also possible. Further, an X-ray diffraction experiment confirmed that the configuration of isatin-derived N-Boc ketimine should be (Z). Confirmation of the configuration of the ketimine would make it easier to understand the rationale for stereofacial selective activation of the electrophile with either organo- or Lewis acid-based catalysts.