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

  1. Vittorio Pace1,2,*,
  2. Wolfgang Holzer1,
  3. Guido Verniest3,4,
  4. Andrés R. Alcántara2,
  5. Norbert De Kimpe4,*

Article first published online: 28 FEB 2013

DOI: 10.1002/adsc.201201043

Issue

Advanced Synthesis & Catalysis

Advanced Synthesis & Catalysis

Volume 355, Issue 5, pages 919–926, March 25, 2013

Additional Information

How to Cite

Pace, V., Holzer, W., Verniest, G., Alcántara, A. R. and De Kimpe, N. (2013), Chemoselective Synthesis of N-Substituted α-Amino-α′-chloro Ketones via Chloromethylation of Glycine-Derived Weinreb Amides. Adv. Synth. Catal., 355: 919–926. doi: 10.1002/adsc.201201043

Author Information

  1. 1

    Department of Drug and Natural Product Synthesis, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria, Fax: (+43)-1-4277-9556; phone: (+43)-1-4277-55623

  2. 2

    Department of Organic and Pharmaceutical Chemistry, Complutense University of Madrid, Pza. Ramón y Cajal s/n, E-28040 Madrid, Spain

  3. 3

    Department of Chemistry, Faculty of Science and Bio-engineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium

  4. 4

    Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium, Fax: (+32)-9-264-6243; phone: (+32)-9-264-5951

*Department of Drug and Natural Product Synthesis, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria, Fax: (+43)-1-4277-9556; phone: (+43)-1-4277-55623

Publication History

  1. Issue published online: 25 MAR 2013
  2. Article first published online: 28 FEB 2013
  3. Manuscript Received: 23 NOV 2012

Funded by

  • University of Vienna

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Keywords:

  • carbenoids;
  • halides;
  • lithiation;
  • nucleophilic substitution;
  • 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.

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