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Chiral Vanadyl(V) Complexes Enable Efficient Asymmetric Reduction of β-Ketoamides: Application toward (S)-Duloxetine
Chien-Tien Chen1, Nabin Ch Maity1, Rachit Agarwal1
1Department of Chemistry, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu 30013, Taiwan.
Abstract:
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.
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