Download PDF
Synthesis 2005(19): 3263-3270  
DOI: 10.1055/s-2005-918481
PAPER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of Quaternary α-Hydroxy Acids by Alkylation of α-Ketoamide-Derived Dienediolates

Rebecca Newton, Stephen P. Marsden*
School of Chemistry, University of Leeds, Leeds, LS2 9JT, UK
Fax: +44(113)3436565; e-Mail: s.p.marsden@leeds.ac.uk;
Further Information

Publication History

Received 6 September 2005
Publication Date:
14 November 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

Double deprotonation of α-ketoamides generates dienediolates, which undergo regioselective α-alkylation to yield α-substituted-α-hydroxy-β,γ-unsaturated amides. 1,2-Disubstituted al­kenes are generated exclusively as the E-isomer. 1,1-Disubstituted and 1,1,2-trisubstituted olefins can also be prepared. The amides can be readily converted to the corresponding acids.

Key words

ketoamides - alkylations - dianions - hydroxy acids - stereoselective­ olefin synthesis

    References

  • 1 Einsle O. Tezcan FA. Andrade SLA. Schmid B. Yoshida M. Howard JB. Rees DC. Science  2002,  297:  1696 
    CrossrefGoogle Scholar
  • 2 Kusano A. Seyama Y. Nagai M. Shibano M. Kusano G. Biol. Pharm. Bull.  2001,  24:  1198 
    CrossrefGoogle Scholar
  • 3 Dawson MJ. Farthing JE. Marshall PS. Middleton RF. O’Neill MJ. Shuttleworth A. Stylli C. Tait RM. Taylor PM. Wildman HG. Buss AD. Langley D. Hayes MV. J. Antibiot.  1992,  45:  639 
    CrossrefGoogle Scholar
  • 4 Tucker H. Crook JW. Chesterson GJ. J. Med. Chem.  1988,  31:  954 
    CrossrefGoogle Scholar
  • 5 Wing KD. Sacher M. Kagaya Y. Tsurubuchi Y. Mulderig L. Connair M. Schnee M. Crop Protection  2000,  19:  537 
    CrossrefGoogle Scholar
  • 6a Naef R. Seebach D. Angew. Chem.  1981,  93:  1113 
    CrossrefGoogle Scholar
  • 6b Seebach D. Naef R. Helv. Chim. Acta  1981,  64:  2704 
    CrossrefGoogle Scholar
  • 6c Seebach D. Aebi JD. Gander-Coquoz M. Naef R. Helv. Chim. Acta  1987,  70:  1194 
    CrossrefGoogle Scholar
  • 7a Boons G.-J. Downham R. Kim K.-S. Ley SV. Woods M. Tetrahedron  1994,  50:  7157 
    CrossrefGoogle Scholar
  • 7b Diez E. Dixon DJ. Ley SV. Angew. Chem. Int. Ed.  2001,  40:  2906 
    CrossrefGoogle Scholar
  • 8 Evans DA. Barrow JC. Leighton JL. Robichaud AJ. Sefkow M. J. Am. Chem. Soc.  1994,  116:  12111 
    CrossrefGoogle Scholar
  • 9 Koft ER. Williams MD. Tetrahedron Lett.  1986,  27:  2227 
    CrossrefGoogle Scholar
  • Lithium halides are known to influence reactivity of lithium amide bases by deaggregation:
  • 10a De Pue JS. Collum DB. J. Am. Chem. Soc.  1988,  110:  5518 
    CrossrefGoogle Scholar
  • 10b De Pue JS. Collum DB. J. Am. Chem. Soc.  1988,  110:  5524 
    CrossrefGoogle Scholar
  • For previous examples of this approach to α-ketoamides, see:
  • 11a Sibi MP. Sharma R. Paulson KL. Tetrahedron Lett.  1992,  33:  1941 
    CrossrefGoogle Scholar
  • 11b Burton AJ. Caldwell KS. Fuchter MJ. Lindvall MK. Patel R. Packham TW. Prodger JC. Schilling MB. Walker MD. Tetrahedron Lett.  2003,  44:  5653 
    CrossrefGoogle Scholar