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 α-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.,Brown, Robert A.,Farnaby, William,Miyatake-Ondozabal, Hideki,Clayden, Jonathan
supporting information; experimental part
p. 2222 - 2225
(2010/08/04)
LIGAND EFFECTS IN ENANTIOFACE DIFFERENTIATING 1,4 ADDITION TO 1,3 DIPHENYL-2 PROPEN-1 ONE
The extent of enantiomeric excess in the β-methylation of chalcone by chiral cuprates is shown to depend strongly on small structural modifications of the ligands, all of which are derived from the basic carbon framework of L-prolinol.Enantiomeric excesses up to 88percent have been realised.