Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate.
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.
Fournier
Anne M
AM
School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Brown
Robert A
RA
Farnaby
William
W
Miyatake-Ondozabal
Hideki
H
Clayden
Jonathan
J
D002219:Carbamates / Q000737:chemistry*; D002974:Clemastine / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D002219:Carbamates; D002974:Clemastine