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Synlett 2006(6): 873-876  
DOI: 10.1055/s-2006-939043
LETTER
© Georg Thieme Verlag Stuttgart · New York

Addition of Lithiated Tertiary Aromatic Amides to Epoxides and Aziridines: Asymmetric Synthesis of (S)-(+)-Mellein

Jonathan Clayden*a, Christopher C. Stimsona, Madeleine Helliwella, Martine Keenanb
a School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK
Fax: +44(161)2754939; e-Mail: clayden@man.ac.uk;
b Eli Lilly & Co. Ltd., Erl Wood Manor, Windlesham, Surrey GU20 6PH, UK
Further Information

Publication History

Received 12 January 2006
Publication Date:
14 March 2006 (online)

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Abstract

Addition of ortholithiated or laterally lithiated amides to epoxides or aziridines provides, in some cases stereoselectively, products which may cyclise to yield benzopyranones in good enantiomeric excess.

Key words

lithiation - directed metallation - synthesis - epoxide - benzopyranone - isochromanone

    References and Notes

  • 1a Gschwend HW. Rodriguez HR. Org. React.  1979,  26:  1 
    Article in Thieme ConnectGoogle Scholar
  • 1b Narasimhan NS. Mali RS. Synthesis  1983,  957 
    Article in Thieme ConnectGoogle Scholar
  • 2 Snieckus V. Chem. Rev.  1990,  90:  879 
    Google Scholar
  • 3 Clark RD. Jahangir A. Org. React.  1995,  47:  1 
    Google Scholar
  • 4 Clayden J. Stimson CC. Keenan M. Synlett  2005,  1716 
    Article in Thieme ConnectGoogle Scholar
  • 5 Fuji K. Kawabata T. Chem. Eur. J.  1998,  373 
    Google Scholar
  • 6 Ahmed A. Bragg RA. Clayden J. Lai LW. McCarthy C. Pink JH. Westlund N. Yasin SA. Tetrahedron  1998,  54:  13277 
    CrossrefGoogle Scholar
  • 7 Watanabe M. Sahara M. Kubo M. Furukawa S. Billedeau RJ. Snieckus V. J. Org. Chem.  1984,  49:  742 
    Google Scholar
  • 8 Comins DL. Brown JD. J. Org. Chem.  1986,  51:  3566 
    Google Scholar
  • 9 Clayden J. Stimson CC. Keenan M. Wheatley AEH. Chem. Commun.  2004,  228 
    CrossrefGoogle Scholar
  • Asymmetry was introduced into a comparable reaction of 2-alkylbenzoate esters by the use of a chiral lithium amide base, see:
  • 10a Regan AC. Staunton J. J. Chem. Soc., Chem. Commun.  1987,  520 
    CrossrefGoogle Scholar
  • 10b Regan AC. Staunton J. J. Chem. Soc., Chem. Commun.  1983,  764 
    CrossrefGoogle Scholar
  • 11 For a comparable strategy using secondary amides, see: Narasimhan NS. Bhide BH. Tetrahedron  1971,  27:  6171 
    CrossrefGoogle Scholar
  • 12 A previous report had indicated lack of reactivity between lithiated tertiary amides and epoxides in the absence of BF3, see: Choukchou-Braham N. Asakawa Y. Lepoittevin J.-P. Tetrahedron Lett.  1994,  35:  3949 
    CrossrefGoogle Scholar
  • 13 The synthesis of alcohols 3 by addition of lithiated amides to aldehydes is in contrast stereoselective with respect to the axis and the benzylic stereogenic centre, but non stereoselective with regard to the relationship between the two centers, see: Clayden J. Pink JH. Westlund N. Frampton CS. J. Chem. Soc., Perkin. Trans. 1  2002,  901 
    CrossrefGoogle Scholar
  • 15a Williams AC. Camp N. Science of Synthesis   Vol. 14:  Thieme; Stuttgart: 2003.  p.347 
    Google Scholar
  • 15b Napolitano E. Org. Prep. Proced. Int.  1997,  29:  631 
    Google Scholar
  • 15c Hill RA. Prog. Chem. Org. Nat. Prod.  1986,  49:  1 
    Google Scholar
  • 16 See: Dimitriadis C. Gill M. Harte MF. Tetrahedron: Asymmetry  1997,  8:  2153 ; and references cited therein
    CrossrefGoogle Scholar
  • 17 Koshino H. Yoshihara T. Okuno M. Sakamura S. Tajimi A. Shimanuki T. Biosci., Biotechnol., Biochem.  1992,  56:  1096 
    CrossrefPubMedGoogle Scholar
  • 18 Clayden J. Mitjans D. Youssef LH. J. Am. Chem. Soc.  2002,  124:  5266 
    CrossrefPubMedGoogle Scholar
  • 19 Andersen KK. Tetrahedron Lett.  1962,  93 
    CrossrefGoogle Scholar
  • 20 Solladié G. Hutt J. Girardin A. Synlett  1987,  1731 
    Google Scholar
14

X-ray crystallographic data have been deposited with the Cambridge Crystallographic Database, reference 288095.

21

Additions of ortholithiated amides to aziridines failed even in the presence of Lewis acids.

22

Crystallographic data have been deposited with the Cambridge Crystallographic database, reference 288094.