Synthesis of (-)-Paroxetine

Significance

A highly diastereoselective addition of a diarylcuprate to an N-acylpyridinium salt bearing a thiazolidine thione chiral auxiliary is the key step in a formal synthesis of (-)-Paroxetine and (+)-Femoxetine. The diastereoselectivity of the addition is rationalized in terms of the intermediate B. The route allowed the selective synthesis of all four diastereoisomers of the 3,4-disubstituted piperidine system.