Download PDF
Synlett 2011(10): 1431-1434  
DOI: 10.1055/s-0030-1260560
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Direct Aldol Reaction of Trifluoromethyl Ketones with Ketones Catalyzed by Et2Zn and Secondary Amines

Shigeru Sasaki, Kasumi Kikuchi, Takayasu Yamauchi, Kimio Higashiyama*
Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
Fax: +81(3)54985768; e-Mail: kimio@hoshi.ac.jp;
Further Information

Publication History

Received 2 March 2011
Publication Date:
13 May 2011 (online)

    Permissions and Reprints All articles of this category

Abstract

The direct catalytic aldol reaction of trifluoromethyl ­ketones with ketones has been accomplished. The reaction was achieved in the presence of 10 mol% Et2Zn and N,N′-dimethylethylenediamine at ambient temperature to give the expected aldol-type products in high yields (up to 99%).

Key words

direct aldol reaction - trifluoromethyl ketone - methyl ketone - diethylzinc - secondary amine

    References and Notes

  • 1a Filler R. Kobayashi Y. Yagupolskii LM. Organofluorine Compounds in Medicinal and Biomedical Applications   Elsevier; Amsterdam: 1993. 
    Google Scholar
  • 1b Banks RE. Smart BE. Tatlow JC. Organofluorine Chemistry; Principles and Commercial Applications   Plenum Press; New York: 1994. 
    Google Scholar
  • 1c Ojima I. McCarthy JR. Welch JT. Biomedical Frontiers of Fluorine Chemistry   ACS Editions; Washington DC: 1996. 
    Google Scholar
  • 2a Kitazume T. Yamazaki T. Experimental Methods in Organic Fluorine Chemistry   Kodansha; Tokyo: 1998. 
    Google Scholar
  • 2b Uneyama K. Organofluorine Chemistry   Blackwell Publishing; Oxford: 2006. 
    Google Scholar
  • 2c Mikami K. Itoh Y. Yamanaka M. Chem. Rev.  2004,  104:  1 
    Google Scholar
  • 2d Shimizu M. Hiyama T. Angew. Chem. Int. Ed.  2005,  44:  214 
    Google Scholar
  • 2e Kitazume T. Matsuda T. Nakamura K. Adv. Org. Synth.  2006,  2:  463 
    Google Scholar
  • 2f Kumadaki I. Yakugaku Zasshi  2006,  126:  1059 
    Google Scholar
  • 2g Santos F. Sanz-Cervera JF. Aceña JL. Sánchez-Roselló M. Synlett  2009,  525 
    Google Scholar
  • 3 Sasaki S. Yamauchi T. Kubo H. Kanai M. Ishii A. Hiagshiyama K. Tetrahedron Lett.  2005,  46:  1497 
    CrossrefGoogle Scholar
  • 4a Mukaiyama T. Banno K. Narasaka K. J. Am. Chem. Soc.  1974,  27:  7503 
    Google Scholar
  • 4b Alcaide B. Almendros P. Eur. J. Org. Chem.  2007,  23:  3916 
    Google Scholar
  • 4c Modern Aldol Reactions   Mahrwald R. Wiley-VCH; Weinheim: 2004. 
    Google Scholar
  • 4d Trost BM. Brindle CS. Chem. Soc. Rev.  2010,  39:  1600 
    Google Scholar
  • For selected examples, see:
  • 5a Torii H. Nakadai M. Ishihara K. Saito S. Yamamoto H. Angew. Chem. Int. Ed.  2004,  43:  1983 
    Google Scholar
  • 5b Funabiki K. Yamamoto H. Nagaya H. Matsui M. Tetrahedron  2006,  62:  5049 
    Google Scholar
  • 5c Funabiki K. Yamamoto H. Nagaya H. Matsui M. Tetrahedron Lett.  2006,  47:  5507 
    Google Scholar
  • 5d Zhang F. Peng Y. Liao S. Gong Y. Tetrahedron  2007,  63:  4636 
    Google Scholar
  • 6a Qiu L.-H. Shen Z.-X. Shi C.-Q. Zhang Y.-W. Chin. J. Chem.  2005,  23:  584 
    Google Scholar
  • 6b Wang X.-J. Zhao Y. Liu J.-Y. Org. Lett.  2007,  9:  1343 
    Google Scholar
  • 6c Wang X.-J. Zhao Y. Liu J.-Y. Synthesis  2008,  3967 
    Google Scholar
  • 7a Kumagai N. Matsunaga S. Yoshikawa N. Ohshima T. Shibasaki M. Org. Lett.  2001,  3:  1539 
    Google Scholar
  • 7b Trost BM. Silcoff ER. Ito H. Org. Lett.  2001,  3:  2497 
    Google Scholar
  • 7c Kumagai N. Matsunaga S. Kinoshita T. Harada S. Okada S. Sakamoto S. Yamaguchi K. Shibasaki M. J. Am. Chem. Soc.  2003,  125:  2169 
    Google Scholar
  • 7d Trost BM. Fettes A. Shireman TB. J. Am. Chem. Soc.  2004,  126:  2660 
    Google Scholar
  • 7e Trost BM. Shin S. Sclafani AJ. J. Am. Chem. Soc.  2005,  127:  8602 
    Google Scholar