Asymmetric reduction of prochiral ketones using 6 in situ generated oxazaborolidine derived from (1S,2S,3R,4R)-3-amino-7,7-dimethoxynorbornan-2-ol. An efficient synthesis of enantiopure (R)-tomoxetine

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-dimethoxynorborman-2-ol (1). The optically active secondary alcohols were generally obtained in moderate to high enantiomeric excesses (ee 43-95%) and good yields (7-5-94%), except for ketones bearing eletron-withdrawing groups. The methodology was applied to the synthesis of enantiopure (R)-tomoxetine. a potent anti-depressant drug. (C) 2004 Elsevier Ltd. All rights reserved.