Download PDF
Synlett 2003(11): 1701-1703
DOI: 10.1055/s-2003-40993
LETTER
© Georg ThiemeVerlag Stuttgart ˙ New York

Stereospecific DearomatisingCyclisation of Tertiary α-Amidoorganolithiums

Jonathan Clayden*, Faye E. Knowles, Christel J. Menet
Department of Chemistry, University of Manchester, Oxford Road,Manchester M13 9PL, UK
Fax: +44(161)2754939; e-Mail: j.p.clayden@man.ac.uk;
Further Information

Publication History

Received 13 March 2003
Publication Date:
05 August 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

Lithiation of benzamides derived from a chiral and enantiomericallypure α-methylbenzylamine leads to diastereoselective andregioselective dearomatising cyclisations with overall conservationof the stereochemistry of the starting stereogenic centre.

Key words

amide; - lithiation - cyclisation - stereospecificity - dearomatisation

    References

  • 1 Basu A. Thayumanavan S. Angew. Chem. Int. Ed.  2002,  41:  716 
    CrossrefPubMedSearch in Google Scholar
  • 2 Carstens A. Hoppe D. Tetrahedron  1994,  50:  6097 
    CrossrefSearch in Google Scholar
  • 3 For discussions concerning configurationalstability and stereospecificity in the reactions of organolithium compounds,see: Clayden J. Organolithiums:Selectivity for Synthesis   Pergamon; Oxford: 2002. 
  • 4 Hammerschmidt F. Hanninger A. Chem. Ber.  1995,  128:  1069 
    CrossrefSearch in Google Scholar
  • 5 Faibish NC. Park YS. Lee S. Beak P. J. Am. Chem. Soc.  1997,  119:  11561 
    CrossrefSearch in Google Scholar
  • 6 Derwing C. Frank H. Hoppe D. Eur.J. Org. Chem.  1999,  3519 
  • 7 Hoppe D. Kaiser K. Stratmann O. Fröhlich R. Meyer O. Hoppe D. Angew. Chem. Int. Ed.  1997,  36:  2784 
    CrossrefSearch in Google Scholar
  • 8 Hoppe D. Kaiser B. Stratmann O. Frohlich R. Angew. Chem. Int. Ed.  1998,  36:  2784 
    Search in Google Scholar
  • 9 Stratmann O. Kaiser B. Frohlich R. Meyer O. Hoppe D. Chem.-Eur.J.  2001,  7:  423 
    CrossrefSearch in Google Scholar
  • 10 Gawley RE. Low E. Zhang Q. Harrris R. J. Am. Chem. Soc.  2000,  122:  3344 
    CrossrefSearch in Google Scholar
  • 11 Gawley RE. TetrahedronLett.  1999,  40:  4297 
    Search in Google Scholar
  • 12a Chiralamido-substituted secondary organolithiumshave been made previously, principally by deprotonation of N-benzyl amides under the influence ofa nearby stereogenic centre or axis (diastereoselective deprotonation:see refs. and: Bragg RA. Clayden J. Menet CJ. Tetrahedron Lett.  2002,  43:  1955 
    CrossrefSearch in Google Scholar
  • 12b The use of a chiral base: Clayden J. Menet CJ. Mansfield DJ. Chem. Commun.  2002,  38 ; or by stereospecific kinetic-isotope-directedlithiation or tin-lithium exchange
    Crossref
  • 13 Ahmed A. Clayden J. Yasin SA. Chem.Commun.  1999,  231 
  • 14 Clayden J. Menet CJ. Mansfield DJ. Org. Lett.  2000,  2:  4229 
    CrossrefSearch in Google Scholar
  • 15 Clayden J. Tchabanenko K. Yasin SA. Turnbull MD. Synlett  2001,  302 
  • 16 For an example of lithiated carbamate unstable towards a stereospecificrearrangement, see: Hara O. Ito M. Hamada Y. TetrahedronLett.  1998,  39:  5537 
    Search in Google Scholar
  • 18 The cyclisation can be interpretedas a nucleophilic attack by the organolithium centre on the aromaticring or as an electrocyclic ring closure, see: Clayden J. Purewal S. Helliwell M. Mantell SJ. Angew. Chem. Int.Ed.  2002,  41:  1091 
    Search in Google Scholar
  • 20 Bragg RA. Clayden J. Tetrahedron Lett.  1999,  40:  8323 
    CrossrefSearch in Google Scholar
  • 21 Bragg RA. Clayden J. Tetrahedron Lett.  1999,  40:  8327 
    CrossrefSearch in Google Scholar
  • 22 Fuji K. Kawabata T. Chem.-Eur. J.  1998,  373 
  • 23 Cuyegkeng MA. Mannschreck A. Chem. Ber.  1987,  120:  803 
    Search in Google Scholar
  • 24 Bowles P. Clayden J. Helliwell M. McCarthy C. Tomkinson M. Westlund N. J. Chem. Soc., Perkin Trans. 1  1997,  2607 
    Crossref
  • 25 Ahmed A. Bragg RA. Clayden J. Lai LW. McCarthy C. Pink JH. Westlund N. Yasin SA. Tetrahedron  1998,  54:  13277 
    CrossrefSearch in Google Scholar
  • 26 Clayden J. Knowles FE. Menet CJ. Tetrahedron Lett.  2003,  44:  3397 
    CrossrefSearch in Google Scholar
17

The X-ray crystal structure of a relatedcyclisation product (see ref. [26] )allows us confidence in assigning both absolute and relative stereochemistryas shown.

19

Clayden, J.; Menet, C. J. Tetrahedron Lett., inpress.