Enantioselective Synthesis of Isoindolinone by Sequential Palladium-Catalyzed Aza-Heck/Suzuki Coupling Reaction

Org Lett. 2024 Dec 23. doi: 10.1021/acs.orglett.4c04239. Online ahead of print.

Abstract

We present a tandem aza-Heck/Suzuki cross-coupling reaction of O-phenyl hydroxamic ethers with readily available arylboronic and alkenyl boronic acids. This protocol is enabled by a palladium catalyst paired with chiral phosphoramidite ligands, particularly under mild reaction conditions, yielding efficient and succinct synthetic routes to chiral isoindolinones with high enantioselectivity. Furthermore, this reaction exhibits excellent functional group compatibility and a rich diversity of subsequent transformations.