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Chemoselective Synthesis of N ‐Substituted α‐Amino‐α′‐chloro Ketones via Chloromethylation of Glycine‐Derived Weinreb Amides
Author(s) -
Pace Vittorio,
Holzer Wolfgang,
Verniest Guido,
Alcántara Andrés R.,
De Kimpe Norbert
Publication year - 2013
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201201043
Subject(s) - chemistry , glycine , yield (engineering) , combinatorial chemistry , aryl , organic chemistry , transformation (genetics) , amino acid , biochemistry , materials science , alkyl , metallurgy , gene
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.