Dynamic kinetic resolution of β′-keto-β-amino esters using Ru-DTBM-Sunphos catalyzed asymmetric hydrogenation

A convenient method for the enantioselective synthesis of β′-hydroxy-β-amino esters was developed through intensive investigations of the reaction conditions. Dichloromethane (DCM)/2,2,2-trifluoroethanol (TFE) and 1,2-dichloroethane (DCE)/TFE combinations were found to be the appropriate co-solvents for the reaction. In this mixed solvent system, [Ru(cymene)Cl2]2-Sunphos exhibited unusually higher activity and selectivity than the corresponding [Ru(cymene)I2]2-Sunphos. In situ generated catalyst could be used for this transformation. Asymmetric hydrogenation of a series of β′-keto-β-amino esters derivatives using Ru-Sunphos complexes via dynamic kinetic resolution led to the corresponding β′-hydroxy-β-amino esters with ee up to 99.6% and de up to 98.8% (S/C=1000).