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Synthesis 2002(13): 1813-1818
DOI: 10.1055/s-2002-33905
PAPER
© Georg Thieme Verlag Stuttgart · New York

A Convenient Synthetic Access to δ-Amino-γ,γ-difluoro-β-ketoesters

Yanli Wang, Shizheng Zhu*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, 200032, China
Fax: +86(21)64166128; e-Mail: zhusz@pub.sioc.ac.cn;
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Publication History

Received 30 April 2002
Publication Date:
09 September 2002 (online)

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Abstract

The zinc-cuprous chloride promoted Reformatsky-imine addition reaction of 4-bromo-4,4-difluoroacetoacetate with ald­imines derived from aromatic aldehydes and with ketimines derived from aryl alkyl ketone provided an efficient and practical access to δ-amino-γ,γ-difluoro-β-ketoesters. The scope and limitation of this procedure are also discussed.

Key words

difluorinated amines - imines - zinc - cuprous chloride - 4-bromo-4,4-difluoroacetoacetate

    References

  • 1a Ojima I. McCarthy JR. Welch JT. Biomedical Frontiers of Fluorine Chemistry   ACS Symposium Series 639; Washington D. C.: 1996. 
    Google Scholar
  • 1b Soloshonok VA. Enantiocontrolled Synthesis of Fluoro-organic Compounds, Stereochemical Challenges and Biomedical Targets   Wiley; Chichester: 1999. 
    Google Scholar
  • 1c Ramachandran PV. Asymmetric Fluoro-oganic Chemistry, Synthesis Applications and Future Directions   ACS Symposium Series 746; Washington D. C.: 2000. 
    Google Scholar
  • 2a Doherty AM. Sircar I. Kornberg BE. Quin J. Winters RT. Kaltenbronn JS. Taylor MO. Bartley BL. Rapundalo SR. Ryan MJ. Painchaud CA. J. Med. Chem.  1992,  35:  2 
    CrossrefGoogle Scholar
  • 2b Bernstein PR. Kosmider BJ. Vacek EP. Veale CA. Gomes BC. Bioorg. Med. Chem. Lett.  1994,  4:  2175 
    CrossrefGoogle Scholar
  • 2c Kukhar VP. Soloshonok VA. Fluorine containing Amino Acids, Synthesis and Properties   Wiley; Chichester: 1995. 
    CrossrefGoogle Scholar
  • 2d Tozer MJ. Herpin TF. Tetrahedron  1996,  52:  8619 
    CrossrefGoogle Scholar
  • 2e Schirlin D. Baltzer S. Altenburger JM. Tarnus C. Remy JM. Tetrahedron  1996,  52:  305 
    CrossrefGoogle Scholar
  • 3 Whitten JP. Barney CL. Huber EW. Bey P. McCarthy JR. Tetrahedron Lett.  1989,  30:  3649 
    CrossrefGoogle Scholar
  • 4 Kodama Y. Okumura M. Yanabu N. Taguchi T. Tetrahedron Lett.  1996,  37:  1061 
    CrossrefGoogle Scholar
  • 5 Percy JM. Prime ME. J. Org. Chem.  1998,  63:  8049 
    CrossrefGoogle Scholar
  • 6 Wang YL. Zhu ZS. Tetrahedron Lett.  2001,  42:  5741 
    CrossrefGoogle Scholar
  • 7a Davies FA. Chao B. Rao A. Org. Lett.  2001,  3:  3169 
    Google Scholar
  • 7b Davies FA. Chao B. Fang T. Szewczyk JM. Org. Lett.  2000,  2:  1041 
    Google Scholar
  • 7c Leflemme N. Dallemagne P. Rault S. Tetrahedron Lett.  2001,  42:  8997 
    Google Scholar
  • 7d Honma T. Tada Y. Adachi I. Igarashi K. J. Heterocycl. Chem.  1989,  26:  629 
    Google Scholar
  • 8a Taguchi T. Kitagawa O. Suda Y. Ohkawa S. Hashimoto A. Iitaka Y. Kokayashi Y. Tetrahedron Lett.  1988,  29:  5291 
    CrossrefGoogle Scholar
  • 8b Baldwin JE. Lynth GP. Schofield CJ. J. Chem. Soc., Chem. Commun.  1991,  736 
    CrossrefGoogle Scholar
  • 8c Baldwin JE. Lynch GP. Schofield CJ. Tetrahedron  1992,  48:  9085 
    CrossrefGoogle Scholar
  • 8d Angelastro MR. Bey P. Mendi S. Peet N. Bioorg. Med. Chem. Lett.  1992,  2:  1235 
    CrossrefGoogle Scholar
  • 8e Uoto K. Ohsuki S. Takenoshita H. Ishiyama T. Iimura S. Hirota Y. Mitsui I. Terasawa H. Soga T. Chem. Pharm. Bull.  1997,  45:  1793 
    CrossrefGoogle Scholar
  • 8f Marcotte S. Pannecoucke X. Feasson C. Quirion J.-C. J. Org. Chem.  1999,  64:  8461 
    CrossrefGoogle Scholar
  • 9 Katritzky AR. Nichols DA. Qi M. Tetrahedron Lett.  1998,  39:  7063 
    CrossrefGoogle Scholar
  • 10a Burton DJ. Easdon JC. J. Fluorine Chem.  1988,  38:  125 
    CrossrefGoogle Scholar
  • 10b Kitagawa O. Taguchi T. Kobayashi Y. Tetrahedron Lett.  1988,  29:  1803 
    CrossrefGoogle Scholar
  • 11 Kuroboshi M. Ishihara T. Tetrahedron Lett.  1987,  28:  6481 
    CrossrefGoogle Scholar
  • 12a Parisi MF. Gattuso G. Notti A. Raymo FM. J. Org. Chem.  1995,  60:  5174 
    Google Scholar
  • 12b Bravo P. Pregnolato M. Resnati G. J. Org. Chem.  1992,  57:  2726 
    Google Scholar
13

Some of the signals in aryl and alkene region are not assigned in 13C NMR spectra due to complexity, since the spectrum is obtained from a mixture of keto ester enol ester and hydrate form.