Insight into Stereocontrol in the Asymmetric Intramolecular Allylation with a tert-Butylsulfinamide Nucleophile: Application in the Synthesis of Chiral Isoindoline-1-Carboxylic Acid Esters.

The asymmetric induction afforded by a chiral sulfinyl group in a palladium/Brønsted-acid-catalyzed intramolecular allylic amination was investigated. Predictions of the diastereoselectivity for various substrates under assumed total thermodynamic control were obtained from density functional theory (DFT), and the correlation with experimental data demonstrates abrupt changes to kinetic control across the substrate scope. The resulting heterocyclic product was readily converted to valuable isoindoline-1-carboxylic acid esters by a two-step oxidation sequence, providing asymmetric access to a key unnatural α-amino acid scaffold.

Palladium/Brønsted-Acid-Catalyzed Diastereoselective Cyclization with Chiral Sulfinamides as Nucleophiles.

This article reports diastereoselective cyclization with chiral sulfinamides as nucleophiles in two reaction pathways: (1) intramolecular allylic substitution and (2) sequential aerobic oxidation with aza-Michael addition. These reactions were enabled by synergistic palladium and Brønsted acid catalysis and produced chiral isoindolines with good yields of 55-92% and high diastereoselectivities of 10:1 to >20:1 dr.