Abstract
Purchase PDF (276 K)
E-mail Article
Add to my Quick Links
Cited By in Scopus (9)
Purchase PDF (160 K)
doi:10.1016/j.tetlet.2004.11.052 
Copyright © 2004 Elsevier Ltd All rights reserved.
Asymmetric reduction of prochiral ketones using in situ generated oxazaborolidine derived from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol. An efficient synthesis of enantiopure (R)-tomoxetine
References and further reading may be available for this article. To view references and further reading you must purchase this article.
Alexandre A.M. Lapisa, Ângelo de Fátimaa, José E.D. Martinsb, Valentim E.U. Costab, 
and Ronaldo A. Pillia, , 
Received 24 July 2004;
Abstract
Catalytic asymmetric reduction of prochiral ketones was examined in the presence of chiral oxazaborolidine catalyst 2 prepared in situ from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol (1). The optically active secondary alcohols were generally obtained in moderate to high enantiomeric excesses (ee 43–95%) and good yields (75–94%), except for ketones bearing electron-withdrawing groups. The methodology was applied to the synthesis of enantiopure (R)-tomoxetine, a potent anti-depressant drug.
Graphical abstract
In this work, we report our results on the asymmetric reduction of prochiral aromatic and aliphatic ketones 3, 5–8 catalyzed by the novel in situ generated oxazaborolidine 2 derived from (1S,2S,3R,4R)-3-amino-7,7-dimethoxybornan-2-ol (1) and BH3·Me2S. This methodology was applied to the synthesis of the anti-depressant drug (R)-tomoxetine in three steps and 47% overall yield from 3-chloropropiophenone (3h).
Keywords: Oxazaborolidine; 3-Amino-7,7-dimethoxynorbornan-2-ol; Asymmetric reduction; Tomoxetine
