ArPNO-Catalyzed Acylative Dynamic Kinetic Resolution of 3-Hydroxyphthalides: Access to Enantioenriched Phthalidyl Esters
Yang-Guang Chen, Heng-Bin Yu, Tian Yin, Cheng Peng, Ming‐Sheng Xie, Hai‐Ming Guo
Abstract
-oxide nucleophilic organocatalyst was used to synthesize chiral phthalidyl ester prodrugs by the acylative dynamic kinetic resolution process. By using the 3,5-dimethylphenyl-derived ArPNO catalyst, the phthalidyl esters were obtained in up to 97% yield with 97% ee at room temperature. Two phthalidyl esters of prodrugs, talosalate and talmetacin, were generated. By control experiments and density functional theory calculations, an acyl transfer mechanism was proposed.
Topics & Concepts
ChemistryKinetic resolutionYield (engineering)NucleophileCatalysisProdrugPyridineArylCombinatorial chemistryOxideKinetic energyOrganic chemistryEnantioselective synthesisThermodynamicsQuantum mechanicsAlkylPhysicsBiochemistryAxial and Atropisomeric Chirality SynthesisAsymmetric Synthesis and CatalysisCoordination Chemistry and Organometallics