Pd-Catalyzed kinetic resolution of benzylic alcohols: a practical synthesis of (R)-tomoxetine and (S)-fluoxetine hydrochlorides

A convenient synthetic route to (R)-tomoxetine hydrochloride (90% ee) and (S)-fluoxetine hydrochloride (84% ee) is described. (S)-3-Phenyl-3-hydroxypropyl p-toluenesulphonate, the key intermediate, is obtained by the oxidative kinetic resolution of the corresponding racemic 3-phenyl-3-hydroxypropyl p-toluenesulphonate using (−)-sparteine/Pd(II)/O2 (1 atm) catalytic system.