Asymmetric Autotandem Palladium-Catalyzed Arylation-Cyclization of Alkene-Tethered N -Tosylimines with Arylboronic Acids Enabled by Planar-Chiral Phosphine-Oxazole Ligands

Asymmetric autotandem catalysis (ATC) has been highly appealing, as a single chiral catalyst facilitates efficient access to enantio-enriched complex molecules from simple achiral starting compounds. However, metal-catalyzed asymmetric ATC remains underdeveloped, and the development of superior chiral ligands is a predominant pillar of metal-catalyzed asymmetric ATC. Herein, we report the asymmetric autotandem palladium-catalyzed arylation-cyclization of alkene-tethered N-tosylimines with arylboronic acids enabled by planar-chiral phosphine-oxazole ligands, providing the chiral cis-1,3-disubstituted isoindolines with high yields and enantio- and diastereoselectivities. In this palladium-catalyzed asymmetric ATC process, planar-chiral bidentate phosphine-oxazole ligands with both electron-donating phosphine and electron-deficient oxazole moieties exhibit dynamic electronic tuning and play a critical role in two catalytic cycles with opposite electronic demands as well as the modulation of enantio- and diastereoselectivity simultaneously. Mechanistic investigations identify the palladium(II)-catalyzed arylation and aminopalladium cyclization autotandem reaction.