Download PDF
Synthesis 2006(10): 1578-1589  
DOI: 10.1055/s-2006-926462
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Halogenated Phenols by Directed ortho-Lithiation and ipso-Iododesilylation Reactions of O-Aryl N-Isopropylcarbamates

Matthias Kauch, Dieter Hoppe*
Westfälische Wilhelms-Universität Münster, Organisch-Chemisches Institut, Corrensstraße 40, 48149 Münster, Germany
Fax: +49(251)8336531; e-Mail: dhoppe@uni-muenster.de;
Further Information

Publication History

Received 23 December 2005
Publication Date:
08 May 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

The regioselective synthesis of halogenated phenols via directed ortho-lithiation reactions of in situ N-silylated O-aryl N-isopropylcarbamates is reported. This protocol is complemented by ipso-iododesilylation reactions of C-silylated carbamates and iodine-magnesium exchange reactions, which are facilitated by the adjacent carbamoyl group. These methods provide an entry into a series of o-fluoro-, o-iodo-, and o,o′-diiodophenols in high yields which are otherwise difficult to obtain.

Key words

electrophilic aromatic substitution - Grignard reactions - halides - lithiation - phenols

    References

  • Reviews:
  • 1a Metal-Catalyzed Cross-Coupling Reactions   2nd ed.:  de Meijere A. Diederich F. Wiley-VCH; Weinheim: 2004. 
    Google Scholar
  • 1b Volume on Cross-coupling Reactions, Top. Curr. Chem.  2002,  219:  1-241  
    Google Scholar
  • 2a Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 
    Google Scholar
  • 2b Special issue on Fluorine in the Life Sciences, ChemBioChem  2004,  5:  557-726  
    Google Scholar
  • 3 Larock RC. Comprehensive Organic Transformations   2nd ed.:  Wiley; New York: 1999.  p.607 
    Google Scholar
  • 4a Nyffeler PT. Durón SG. Burkart MD. Vincent SP. Wong C.-H. Angew. Chem. Int. Ed.  2005,  44:  192 
    CrossrefPubMedGoogle Scholar
  • 4b Lal GS. Pez GP. Syvret RG. Chem. Rev.  1996,  96:  1737 
    CrossrefPubMedGoogle Scholar
  • For reviews, see:
  • 5a Snieckus V. Chem. Rev.  1990,  90:  879 
    Google Scholar
  • 5b Hartung CG. Snieckus V. In Modern Arene Chemistry   Astruc D. Wiley-VCH; Weinheim: 2002.  p.330 
    Google Scholar
  • 5c Clayden J. In The Chemistry of Organolithium Compounds   Rappoport Z. Marek I. Wiley; Chichester: 2004.  p.495 
    Google Scholar
  • 5d Gribble GW. In Science of Synthesis   Vol. 8a:  Majewski M. Snieckus V. Thieme; Stuttgart: 2006.  p.357 
    Google Scholar
  • 6a Kauch M. Hoppe D. Can. J. Chem.  2001,  79:  1736 
    CrossrefPubMedGoogle Scholar
  • 6b Kauch M. Snieckus V. Hoppe D. J. Org. Chem.  2005,  70:  7149 
    CrossrefPubMedGoogle Scholar
  • 7 Christensen H. Synth. Commun.  1975,  5:  65 
    Google Scholar
  • 8 Sibi MP. Snieckus V. J. Org. Chem.  1983,  48:  1935 
    CrossrefGoogle Scholar
  • For metalation studies of MOM protected mono- and difluorophenols, see:
  • 9a Marzi E. Mongin F. Spitaleri A. Schlosser M. Eur. J. Org. Chem.  2001,  2911 
    Article in Thieme ConnectGoogle Scholar
  • 9b Marzi E. Gorecka J. Schlosser M. Synthesis  2004,  1609 
    Article in Thieme ConnectGoogle Scholar
  • 10 Baker AW. Shulgin AT. Can. J. Chem.  1965,  43:  650 
    CrossrefGoogle Scholar
  • General reviews on arylsilanes and their application in organic synthesis:
  • 11a Keay BA. In Science of Synthesis   Vol. 4:  Fleming I. Thieme; Stuttgart: 2002.  p.685 
    Google Scholar
  • 11b Bassindale AR. Glynn SJ. Taylor PG. In The Chemistry of Organic Silicon Compounds   Vol. 2:  Rappoport Z. Apeloig Y. Wiley; Chichester: 1998.  p.355 
    Google Scholar
  • 12 Kauch M. Hoppe D. Synthesis  2006,  xxx 
    Google Scholar
  • Compounds 13a and 13b have been synthesized previously in low yields by direct formylation of the 2-halophenols:
  • 13a Feldman KS. Eastman KJ. Lessene G. Org. Lett.  2002,  4:  3525 
    Google Scholar
  • 13b Mcgarrigle EM. Murphy DM. Gilheany DG. Tetrahedron: Asymmetry  2004,  15:  1343 
    Google Scholar
  • For alternative routes via ozonolysis of benzofurans, see:
  • 13c Crich D. Grant D. J. Org. Chem.  2005,  70:  2384 
    Google Scholar
  • 13d Ishii H. Ohta S. Nishioka H. Hayashida N. Harayama T. Chem. Pharm. Bull.  1993,  41:  1166 
    Google Scholar
  • 14 For ipso-substitutions of DoM-derived arylsilanes including O-aryl N,N-diethylcarbamates, see: Zhao Z. Snieckus V. Org. Lett.  2005,  7:  2523 ; and references cited therein
    CrossrefGoogle Scholar
  • 15 Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley; New York: 1999.  p.249 
    Google Scholar
  • 16 Similar results were reported for a related system: Takahashi M. Hatano K. Kimura M. Watanabe T. Oriyama T. Tetrahedron Lett.  1994,  35:  579 
    CrossrefGoogle Scholar
  • For 26a, see:
  • 17a Weeratunga G. Horne S. Rodrigo R. J. Chem. Soc., Chem. Commun.  1988,  721 
    CrossrefGoogle Scholar
  • For 26c, see:
  • 17b Cambie RC. Rutledge PS. Smith-Palmer T. Woodgate PD. J. Chem. Soc., Perkin Trans. 1  1976,  1161 
    CrossrefGoogle Scholar
  • 18 For 28a, see: Vasil’ev AA. Engman L. J. Org. Chem.  1998,  63:  3911 
    CrossrefGoogle Scholar
  • 19a Boymond L. Rottländer M. Cahiez G. Knochel P. Angew. Chem. Int. Ed.  1998,  37:  1701 
    Article in Thieme ConnectGoogle Scholar
  • For reviews, see:
  • 19b Knochel P. Dohle W. Gommermann N. Kneisel FF. Kopp F. Korn T. Sapountzis I. Vu VA. Angew. Chem. Int. Ed.  2003,  42:  4302 
    Article in Thieme ConnectGoogle Scholar
  • 19c Jensen AE. Dohle W. Sapountzis I. Lindsay DM. Vu VA. Knochel P. Synthesis  2002,  565 
    Article in Thieme ConnectGoogle Scholar