Chemoselective Synthesis of N ‐Substituted α‐Amino‐α′‐chloro Ketones via Chloromethylation of Glycine‐Derived Weinreb Amides

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.