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Synthesis 2009(6): 891-902  
DOI: 10.1055/s-0028-1087972
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Electrophilic ipso-Halocyclization of N-Arylpropynamides with Polyfluoro­alkyl Alcohols: Selective Synthesis of 8-(Polyfluoroalkoxy)azaspiro[4.5]trienes

Zhi-Qiang Wanga, Bo-Xiao Tanga, Hong-Ping Zhanga,b, Feng Wanga, Jin-Heng Li*a
a Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, P. R. of China
Fax: +86(731)8872101; e-Mail: jhli@hunnu.edu.cn;
b Department of Biology and Chemical Engineering, Shaoyang University, Shaoyang 422000, P. R of China
Further Information

Publication History

Received 19 September 2008
Publication Date:
24 February 2009 (online)

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Abstract

A novel and efficient method for the synthesis of 8-(polyfluoroalkoxy)-1-azaspiro[4.5]deca-3,6,9-trien-2-ones has been demonstrated via the electrophilic ipso-halocyclization of N-arylpropynamides with polyfluoroalkyl alcohols. In the presence of N-halosuccinimides (NXS), a variety of N-arylpropynamides underwent an electrophilic ipso-halocyclization reaction with poly­fluoroalkyl alcohols to afford the corresponding 8-(polyfluoroalkoxy)spiro[4.5]trienes in good yields. Note that molecular sieves can improve the yield of the reaction.

Key words

electrophilic ipso-halocyclization - N-arylpropynamide - N-halosuccinimide - spiro[4.5]decane - polyfluoroalkoxy substitution

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A set of other reagents, including NaOEt, NaOAc, NH4Cl, 4-nitrophenol, and TfOH, instead of TFA were examined. The results showed that no reaction was observed using NaOEt, NaOAc, NH4Cl, or 4-nitrophenol, and the electrophilic ortho-cyclization product 4aa was obtained in 90% yield in the presence of TfOH.