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

Desymmetrizations of the prochiral bis(bromoaryl)alcohols I and 4 were effected by treatment with iPr(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, 5.1% yield). The latter was converted into (R)-orphenadrine, an antihistaminic and anticholinergic drug