Chemoselective synthesis of N-substituted α-amino-α′- chloro ketones via chloromethylation of glycine-derived Weinreb amides

Abstract

Functionalized α-arylamino-α′-chloro ketones are obtained in high yield via a straightforward homologation reaction of Weinreb amides derived from N-arylglycines using in situ generated chloromethyllithium. The use of the Weinreb amides is essential and allows the chemoselective homologation of N-aryl-N-substituted glycine analogues, a transformation which is not possible using similar glycine esters. The procedure is promising for the large-scale preparation of α-amino-α′-chloropropanones, which are valuable precursors for a variety of bioactive compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.