Download PDF
Synlett 2009(16): 2673-2675  
DOI: 10.1055/s-0029-1217954
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective O-Alkylations of Indazolinone Using (Cyanomethylene)triphenylphosphorane

Amy Randall*, Florine Duval
Research Chemistry, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK
Fax: +44(1304)651821; e-Mail: Amy.Randall@pfizer.com;
Further Information

Publication History

Received 23 April 2009
Publication Date:
04 September 2009 (online)

    Permissions and Reprints All articles of this category

Abstract

Regioselective O-alkylation of indazolinones using (cyanomethylene)-triphenthylphosphorane (CMPP) as a Mitsunobu-type reagent is described with a variety of aliphatic alcohols. This method was also successfully applied to the N-alkylation of O-protected indazolinone. Selective N1 and N2 alkylations on indazolinone have previously been described; our methodology is therefore orthogonal to the previous precedent.

Key words

alkylations - heterocycles - ylides - Mitsunobu - trialkyl­phosphoranes

    References and Notes

  • 1a Malamas MS. Millen J. J. Med. Chem.  1991,  34:  1492 
    Google Scholar
  • 1b Aran VJ. Diez-Barra E. De la Hoz A. Sanchez-Verdu P. Heterocycles  1997,  45:  129 
    Google Scholar
  • 2 Eacho PI, Foxworthy-Mason PS, Lin H, Lopez J, Moslor MK, and Richett ME. inventors; WO  2004093872. 
  • 3 Gordon DW. Synlett  1998,  1065 
    Article in Thieme ConnectGoogle Scholar
  • 4 Arb VJ. Flores M. Muiioz P. Paez JA. Sanchez-Verdul P. Stud M. Liebigs Ann.  1996,  683 
    Google Scholar
  • 5 Selwood DL. Brummell DG. Budworth J. Burtin GE. Campbell RO. Chana SS. Charles IG. Fernandez PA. Glen RC. Goggin MC. Hobbs AJ. Kling MR. Liu Q. Madge DJ. Meillerais S. Powell KL. Reynolds K. Spacey GD. Stables JN. Tatlock MA. Wheeler KA. Wishart G. Woo C. J. Med. Chem.  2001,  44:  78 
    CrossrefPubMedGoogle Scholar
  • 6 Mitsunobu O. Yamanda M. Mukaiyama T. Bull. Chem. Soc. Jpn.  1967,  40:  935 
    CrossrefPubMedGoogle Scholar
  • 7 Tsunoda T. Otsuka J. Yamamita Y. Ito S. Chem. Lett.  1994,  539 
    CrossrefGoogle Scholar
  • 9 A more detailed review of the mechanism can be found in: McNulty J. Capretta A. Laritchev V. Dyck J. Robertson AJ. Angew. Chem. Int. Ed.  2003,  42:  4051 
    CrossrefGoogle Scholar
  • 10 Sakamoto I. Kaku H. Tsunoda T. Chem. Pharm. Bull.  2003,  51:  474 
    CrossrefPubMedGoogle Scholar
  • 11 Bombrun A. Casi G. Tetrahedron Lett.  2002,  43:  2187 
    CrossrefGoogle Scholar
  • 12a Uemoto K. Kawahito A. Matsushita N. Sakamoto I. Kaku H. Tsunoda T. Tetrahedron Lett.  2001,  42:  905 
    Google Scholar
  • 12b Tsunoda T. Uemoto K. Ohtani T. Kaku H. Ito S. Tetrahedron Lett.  1999,  40:  7359 
    Google Scholar
  • 13 Golantsov NE. Karachava AV. Yurovskaya MA. Chem. Heterocycl. Compd. (N.Y., NY, U.S.)  2008,  44:  263 
    CrossrefGoogle Scholar
  • 14 Tsunods T. Ozaki F. Ini S. Tetrahedron Lett.  1994,  35:  5081 
    CrossrefGoogle Scholar
  • 15a Manivel P. Rai NP. Jayashankara VP. Arunachalam PN. Tetrahedron Lett.  2007,  48:  2701 
    Google Scholar
  • 15b Tsunods T. Ozaki F. Ini S. Tetrahedron Lett.  1994,  35:  5081 
    Google Scholar
  • 15c Zong K. Groenendaal L. Reynolds JR. Tetrahedron Lett.  2006,  47:  3521 
    Google Scholar
  • 18 Aran VJ. Flores M. Munoz P. Paez JA. Sanchez-Verdu P. Stud M. Liebig. Ann.  1996,  683 
    Google Scholar
8

These reactions were not heated for safety reasons and this is probably why unlike Selwood (ref. 5) we saw no reaction.

16

ACD PK a predictor suggests (Figure  [³] )

Figure 3

17

NMR and LC-MS data confirm that 6a and 7a are diasteromers. Based on mechanism inversion in assumed, but this has not been confirmed experimentally.