Nucleophilic addition of methyllithium to chiral oxime ethers: asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue

Chiral (E)-arylaldehyde oxime ethers, prepared using (R)-1-phenyl-1,2-ethanediol as a chiral auxiliary. undergo nucleophilic addition with methyllithium to give diastereomerically enriched O-alkyl hydroxylamines which, after reductive N-O bond cleavage, lead to the corresponding (R)-1-(aryl)ethylamines. This methodology has been applied to the enantioselective synthesis of a new type of arylalkylamine calcimimetics (R)-(+)-NPS R-568 and its thio analogue. (C) 2001 Elsevier Science Ltd. All rights reserved.