Synthesis of (R)-Orphenadrine

Significance

Orphenadrine is an antihistamine and anticholinergic drug. Sälinger and Brückner report a short synthesis of (R)-orphenadrine that features the first asymmetric ligand-accelerated halogen-metal exchange in which the pro-S bromoarene of the substrate B reacts faster than the pro-R bromoarene leading to kinetic selection for the organomagnesium derivative D. Simple protonolysis of D gave the key intermediate E.