Download PDF
Synthesis 2012(2): 247-252  
DOI: 10.1055/s-0031-1289629
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Enantio- and Diastereoselective Synthesis of β,γ,γ,δ-Tetrasubstituted α-Methylene-δ-lactones

Łukasz Albrechta, Dariusz Deredasa, Jakub Wojciechowskib, Wojciech M. Wolfb, Henryk Krawczyk*a
a Institute of Organic Chemistry, Technical University (Politechnika), Żeromskiego 116, 90-924 Łódź, Poland
Fax: +48(42)63655 30; e-Mail: henkrawc@p.lodz.pl;
b Institute of General and Ecological Chemistry, Technical University (Politechnika), Żeromskiego 116, 90-924 Łódź, Poland
Further Information

Publication History

Received 5 September 2011
Publication Date:
01 December 2011 (online)

   Permissions and Reprints All articles of this category
Preview

Abstract

The synthesis of two α-(diethoxyphosphoryl)-α,β-unsaturated δ-lactones with 98% ee has been developed using (S)-3-aryl-3-hydroxy-2,2-dimethylpropanals, easily accessible via direct, asymmetric organocatalytic aldol reaction, as the starting materials. The lactones were transformed into the corresponding α-methylene-δ-lactones in a two-step process involving Michael addition followed by Horner-Wadsworth-Emmons olefination without loss of enantiomeric purity. Furthermore, it was shown that diastereoselectivity of the Michael addition can be fully controlled by the C6 stereogenic center in the intermediate lactones. A transition-state model rationalizing the stereochemical outcome of the reaction was proposed.

Key words

Knoevenagel condensation - Michael addition - HWE olefination - β-hydroxyaldehydes - α-methylene-δ-lactones

    References

  • 1a Kupchan SM. Hemingway RJ. Werner D. Karim A. McPhail AT. Sim GA. J. Am. Chem. Soc.  1968,  90:  3596 
    Search in Google Scholar
  • 1b Cane DE. Rossi T. Tetrahedron Lett.  1979,  20:  2973 
    Search in Google Scholar
  • 1c Nangia A. Prasuna G. Rao PB. Tetrahedron  1997,  53:  14507 
    Search in Google Scholar
  • 1d Liao X.-B. Han J.-Y. Li Y. Tetrahedron Lett.  2001,  42:  2843 
    Search in Google Scholar
  • 1e Ekthawatchai S. Kamchonwongpaisan S. Kongsaeree P. Tarnchompoo B. Thebtaranonth Y. Yuthavong Y. J. Med. Chem.  2001,  44:  4688 
    Search in Google Scholar
  • 1f Avery MA. Alvim-Gaston M. Vroman JA. Wu B. Ager A. Peters W. Robinson BL. Charman W. J. Med. Chem.  2002,  45:  4321 
    Search in Google Scholar
  • 1g Weinheimer AJ. Chang CWJ. Matson JA. Fortschr. Chem. Org. Naturst.  1979,  36:  285 
    Search in Google Scholar
  • 1h McMurry JE. Dushin RG. J. Am. Chem. Soc.  1990,  112:  6942 
    Search in Google Scholar
  • 2a Le Menn JC. Tallec A. Sarrazin J. Can. J. Chem.  1991,  69:  761 
    Search in Google Scholar
  • 2b Demuth M. Schaffner K. Angew. Chem., Int. Ed. Engl.  1982,  21:  820 
    Search in Google Scholar
  • 2c Takeda K. Imaoka I. Yoshii E. Tetrahedron  1994,  50:  10839 
    Search in Google Scholar
  • 2d Solladié G. Boeffel D. Maignan J. Tetrahedron  1995,  51:  9559 
    Search in Google Scholar
  • 2e Solladié G. Boeffel D. Maignan J. Tetrahedron  1996,  52:  2065 
    Search in Google Scholar
  • 2f Raju R. Allen LJ. Le T. Taylor CD. Howell AR. Org. Lett.  2007,  9:  1699 
    Search in Google Scholar
  • 3a Krawczyk H. Œliwiński M. Wolf WM. Bodalski R. Synlett  2004,  1995 
  • 3b Krawczyk H. Œliwiński M. Kūdzia J. Wojciechowski J. Wolf WM. Tetrahedron: Asymmetry  2006,  17:  908 
    Search in Google Scholar
  • 3c Krawczyk H. Œliwiński M. Kūdzia J. Wojciechowski J. Wolf WM. Tetrahedron: Asymmetry  2007,  18:  2712 
    Search in Google Scholar
  • 4 Albrecht Ł. Richter B. Krawczyk H. Jørgensen KA. J. Org. Chem.  2008,  73:  8337 
    Search in Google Scholar
  • 5a Falsone G. Spur B. Liebigs Ann. Chem.  1981,  565 
  • 5b Falsone G. Wingen U. Wendisch D. Tetrahedron Lett.  1989,  30:  675 
    Search in Google Scholar
  • 6 Chen X. Wiemer DF. J. Org. Chem.  2003,  68:  6597 
    Search in Google Scholar
  • 7 Mase N. Tanaka F. Barbas CF. Angew. Chem. Int. Ed.  2004,  43:  2420 
    Search in Google Scholar
  • 8 Boeyens JCA. J. Cryst. Mol. Struct.  1978,  8:  317 
    Search in Google Scholar
  • 9 Cremer D. Pople JA. J. Am. Chem. Soc.  1975,  97:  1354 
    Search in Google Scholar
  • 10 Wojciechowski J. Krawczyk H. Œliwiński M. Kafarska K. Wolf WM. Acta Crystallogr., Sect. C  2007,  63:  o280 
    Search in Google Scholar
  • 11 Allen FH. Watson DG. Brammer L. Orpen AG. Taylor R. In International Tables for Crystallography   Vol. C:  Prince E. Kluwer; Dordrecht: 2004.  p.790-811  
    Search in Google Scholar
  • 13 Flack HD. Acta Crystallogr., Sect. A  1983,  39:  876 
    Search in Google Scholar
  • 14 Bruker APEX2, Version 2010/3   Bruker AXS; Madison (WI, USA): 2010. 
  • 15 Bruker SAINT-Plus, Version 7.68A   Bruker AXS; Madison (WI, USA): 2009. 
  • 16 Bruker SADABS - Bruker Nonius area detector scaling and absorption correction, Version 2008/1   Bruker AXS; Madison (WI, USA): 2008. 
  • 17 Sheldrick GM. SHELXTL Version 2008/4   Bruker AXS; Madison (WI, USA): 2008. 
12

Crystallographic data (excluding structure factors) for the structure reported herein have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC 822405. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK. Any request should be accompanied by a full literature citation.