title: The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.
abstract: Desymmetrizations of the prochiral bis(bromoaryl)alcohols 1 and 4 were effected by treatment with iPr2Mg 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.
authors.affiliation: Institut für Organische Chemie und Biochemie, Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sälinger
authors.forename: Reinhard
authors.initials: R
authors.lastname: Brückner
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D018680:Cholinergic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D006219:Halogens; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006842:Hydrocarbons, Brominated / Q000737:chemistry; D008094:Lithium / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D015394:Molecular Structure; D009966:Orphenadrine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D018680:Cholinergic Antagonists; D006219:Halogens; D006633:Histamine Antagonists; D006842:Hydrocarbons, Brominated; D008094:Lithium; D009966:Orphenadrine; D008274:Magnesium