Anhydrides as Acylating Agents in the Enzymatic Resolution of an Intermediate of (−)-Paroxetine

A new chemoenzymatic method for the preparation of an intermediate of (−)-Paroxetine is reported. Cyclic anhydrides are used as acylating agents in the lipase-catalyzed esterification of <i>trans</i>-4-(4‘-fluorophenyl)-3-hydroxymethyl-<i>N</i>-phenyloxycarbonylpiperidine in organic solvents. The best enantioselectivities are obtained with two different lipases from<i> Candida antarctica</i>. These two lipases show opposite stereochemical preference in these processes, so that both enantiomers can be obtained in their optically pure forms. The (3<i>S</i>,4<i>R</i>) isomer is an intermediate for the synthesis of (−)-Paroxetine.