Download PDF
Synlett 2002(9): 1556-1557
DOI: 10.1055/s-2002-33540
SPOTLIGHT
© Georg Thieme Verlag Stuttgart · New York

The N-Cumyl Group for Facile Manipulation of Carboxamides, Sulfonamides and Aryl O-Carbamates
Post-Directed ortho Metalation

Costa Metallinos*
Boston College Chemistry Department, Merkert Center, 2609 Beacon St., Chestnut Hill, MA 02467, USA
e-Mail: metallin@bc.edu;
Further Information

Publication History

Publication Date:
17 September 2002 (online)

   Permissions and Reprints All articles of this category

Directed metalation groups (DMGs) are sometimes compromised by the inability to convert them to different functionalities under mild conditions in post-directed ortho metalation (DoM) steps. [1] The advent of N-cumyl modified carboxamide, sulfonamide and O-carbamate DMGs, [2] whose primary advantages over analogous N-t-Bu [3] and other N-alkyl systems rest in fast and/or mild hydrolysis post-DoM, has opened new possibilities for the manipulation of substituted aromatics (Scheme 1). Starting materials are easily prepared by treating the appropriate benzoyl or sulfonyl chlorides with cumyl amine [4] for access to benzamides and sulfonamides, respectively, or by treating phenyl chloroformate with a secondary N-alkyl-N-cumyl amine [5] for O-carbamates.

This Spotlight reviews several applications of N-cumyl-substituted functional groups in organic synthesis since the preliminary results of 1999. [2]

Scheme 1

    References

  • 1a Snieckus V. Chem. Rev.  1990,  90:  879 
    CrossrefGoogle Scholar
  • 1b Cuevas J.-C. Patil P. Snieckus V. Tetrahedron Lett.  1989,  30:  5841 
    CrossrefGoogle Scholar
  • 2 Metallinos C. Nerdinger S. Snieckus V. Org. Lett.  1999,  1:  1183 
    CrossrefGoogle Scholar
  • 3 More forcing conditions are required to dealkylate N-t-Bu benzamides; see: Reitz DB. Massey SM. J. Org. Chem.  1990,  55:  1375 
    Google Scholar
  • 4a Cumyl amine can be prepared from cumyl alcohol by a modification of the procedure of: Balderman D. Kalir A. Synthesis  1978,  24 . The azide is reduced with LiAlH4 (Et2O/0 °C → r.t. → reflux) or H2 (Lindlar’s catalyst/EtOH) instead of Raney nickel
    Article in Thieme ConnectGoogle Scholar
  • 4b

    Cumyl amine is also commercially available from TCI America: catalogue no. C1293.
    Article in Thieme Connect
  • 5 Melnick M. Reich SH. Lewis KK. Mitchell JLJ. Nguyen D. Trippe AJ. Dawson H. Davies JF. Appelt K. Wu B. Musick L. Gehlhaar DK. Webber S. Shetty B. Kosa M. Kahil D. Andrada D. J. Med. Chem.  1996,  39:  2795 
    CrossrefGoogle Scholar
  • 6 Charette AB. Chua P. Synlett  1998,  163 
    Article in Thieme ConnectGoogle Scholar
  • 8 Chao W. Weinreb SM. Tetrahedron Lett.  2000,  41:  9199 
    CrossrefGoogle Scholar
  • 9 Clayden J. Menet CJ. Mansfield DJ. Org. Lett.  2000,  2:  4229 
    CrossrefGoogle Scholar
  • 10 Clayden J. Tchabanenko K. Chem. Commun.  2000,  317 
    CrossrefGoogle Scholar
  • 11 Metallinos C. Ph.D. Thesis   Queen’s University; Kingston, Ontario, Canada: 2001. 
    Google Scholar
  • 12 Tsukazaki M. Tinkl M. Roglans A. Chapell BJ. Taylor NJ. Snieckus V. J. Am. Chem. Soc.  1996,  118:  685 
    Google Scholar
  • 13 Laufer RS. Veith U. Taylor NJ. Snieckus V. Org. Lett.  2000,  2:  629 
    Google Scholar
7

Ang, P. J. A.; Metallinos, C.; Snieckus, V., unpublished results.

14

Metallinos, C.; Szillat, H.; Taylor, N. J.; Snieckus, V., manuscript in preparation.