From Paracetamol to Rolipram and Derivatives: Application of Deacetylation-Diazotation Sequences and Palladium-Catalyzed Matsuda-Heck Reaction

A six-step synthesis of the antidepressant rolipram from the popular analgetic 4-acetamidophenol (paracetamol) is described. The steps include oxidative functionalization of the aromatic core, diazonium salt formation via deacetylation-diazotation, Matsuda-Heck reaction, conjugate addition of nitromethane, and hydrogenative cyclization.