Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of β-Ketoamides: Application toward ( S )-Duloxetine.

High-valent chiral oxidovanadium(V) complexes derived from 3,5-substituted- N -salicylidene-l- tert -leucine were used as catalysts in asymmetric reduction of N -benzyl-β-ketoamides. Among six different solvents, three different alcohol additives, and two different boranes examined, the use of pinacolborane in tetrahydrofuran (THF) with a t -BuOH additive led to the best results at -20 °C. The corresponding β-hydroxyamides can be furnished with yields up to 92% and an enantiomeric excess (ee) up to 99%. We have successfully extended this catalytic protocol for the synthesis of an ( S )-duloxetine precursor.