(−)-Paroxetine hydrochloride was produced asymmetrically in seven steps starting from 4-fluorobenzaldehyde. The stereocenter at C-4 was initially set through desymmetrization of glutaric acid bis methyl ester 4 by PLE hydrolysis. A unique one-pot reduction–alkylation procedure was then developed to provide entry to lactam 2 with the appropriate absolute stereochemistry.
