Abstract: (S)-γ-aminoalcohol is a key intermediate for the preparation of Duloxetine. In this paper, we describe an effective method to obtain (S)-γ-aminoalcohol through asymmetric transfer hydrogenation with an easy accessible (S,S)-TsDPEN-Ru complex as catalyst in HCOOH/Et3N system. A variety of β-amino ketones were examined. β-Amino ketones with donating groups(3a~3c) decomposed to give 1-(2-thienyl)-1-propanone during the reaction. On the other hand, (S)-γ-aminoalcohols with withdrawing groups(4e,4f) were obtained in high e.e. values(>95% e.e.) and good yields under optimal reaction conditions. This novel procedure was applied in the asymmetric total synthesis of Duloxetine as a key step. Starting from acetyl thiophene, Duloxetine was obtained in 69% yield and 91.7% e.e..

Key words: Duloxetine, Asymmetric transfer hydrogenation, (S,S)-TsDPEN-Ru complex