The First Asymmetric Halogen/Metal‐Exchange Reaction: Desymmetrization of Alcohols with Enantiotopic Bromoarene Substituents

Abstract Choosy organomagnesium : Prochiral bis(bromoaryl)alcohols were desymmetrized by treatment with i Pr 2 Mg and an enantiopure Li salt. The resulting arylmagnesium intermediate was trapped with electrophiles. Protonolysis and two follow‐up reactions provided the antihistaminic and anticholinergic drug ( R )‐orphenadrine (see scheme). magnified image Desymmetrizations of the prochiral bis(bromoaryl)alcohols 1 and 4 were effected by treatment with i Pr 2 Mg and enantiomerically pure lithium alkoxides. The resulting arylmagnesium compounds were quenched with various electrophiles. The absolute and (if relevant) relative configurations of the resulting products were determined. The best ee /yield combination was obtained for the protonolysis furnishing monobromoalcohol ( R )‐ 2 (53 % ee , 51 % yield). The latter was converted into ( R )‐orphenadrine, an antihistaminic and anticholinergic drug.