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

Abstract

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.

Desymmetrization of Cyclohexadienones through Phase-Transfer-Catalyzed Stereoselective Intramolecular Aza-Michael Addition with Chiral Sulfinamide Nucleophiles

“…In continuation of our research interests in catalytic methodologies for the asymmetric synthesis of heterocyclic compounds, herein we conducted a phase-transfer catalysis (PTC)-enabled stereoselective aza-Michael addition involving the use of a tethered chiral sulfinamide nucleophile for the desymmetrization of cyclohexadienones (Scheme c) . The PTC that incorporates quaternary ammonium salts (R 4 N + X – ) and CsF avoids the use of a strong base and enhances the stereoselectivity manifolds in the aza-Michael reactions.…”