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

Abstract

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.