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

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).