The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.
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.
Sälinger
Daniel
D
Institut für Organische Chemie und Biochemie, Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany.
Brückner
Reinhard
R
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
D000438:Alcohols; D018680:Cholinergic Antagonists; D006219:Halogens; D006633:Histamine Antagonists; D006842:Hydrocarbons, Brominated; D008094:Lithium; D009966:Orphenadrine; D008274:Magnesium