Synergistic Palladium/Chiral Phosphoric Acid-Catalyzed Kinetic Resolution via Stereoselective Intramolecular Substitution of Unactivated Allylic Alcohols

This paper reports the kinetic resolution of racemic secondary alcohols ( O -nucleophiles) via stereoselective intramolecular allylic substitution. The reaction was enabled by synergistic palladium and chiral phosphoric acid catalysis and produced chiral cis -1,3-disubstituted 1,3-dihydroisobenzofurans with a selective factor of up to 60.9 and a diastereomeric ratio of up to 7.8:1. Asymmetric synthesis of a compound with antihistaminic activity was demonstrated as the application of this methodology.