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

Chien-Tien Chen, Nabin Ch. Maity, Rachit Agarwal, Chien-Fu Lai, Yiya LiaoWei-Ru Yu
Journal of Organic Chemistry, 卷.85(10), 頁碼.6408-6419
05/2020

摘要

Organic Chemistry
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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