Asymmetric Synthesis of 1,3-Disubstituted Isoindolines via a Palladium-Catalyzed Arylation/Aza-Michael Addition Cascade

Facile access to chiral cis -1,3-disubstituted isoindolines via a palladium-catalyzed arylation/aza-Michael addition cascade of ε -iminoenoates with arylboronic acids has been achieved. This strategy features high yields, excellent chemo-, diastereo-, and enantioselectivities, and a broad substrate scope. Mechanistic studies illustrate that this reaction is a cascade involving asymmetric arylation to deliver the chiral aminoenoate intermediates and sequential base-promoted aza-Michael addition. Silver acetate plays a crucial role in the palladium-catalyzed asymmetric arylation of sterically hindered ε -iminoenoates.