title: Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate.
abstract: The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of alpha-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.
authors.affiliation: School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fournier
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brown
authors.forename: William
authors.initials: W
authors.lastname: Farnaby
authors.forename: Hideki
authors.initials: H
authors.lastname: Miyatake-Ondozabal
authors.forename: Jonathan
authors.initials: J
authors.lastname: Clayden
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D002974:Clemastine / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D002219:Carbamates; D002974:Clemastine