Copper mediated defluorinative allylic alkylation of difluorohomoallyl alcohol derivatives directed to an efficient synthetic method for ( Z)-fluoroalkene dipeptide isosteres

[Display omitted] ► High yield and highly Z selective allylic alkylation reaction of difluorohomoally alcohol derivatives with Grignard reagents and CuI catalyst leading to fluoroallyl alcohol derivatives. ► Complete 1,3-chirality transfer in the imidate Claisen rearrangement of the above fluoroally...

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Bibliographic Details
Published in:Journal of fluorine chemistry 2011-05, Vol.132 (5), p.327-338
Main Authors: Watanabe, Daisuke, Koura, Minoru, Saito, Akio, Yanai, Hikaru, Nakamura, Yuko, Okada, Midori, Sato, Azusa, Taguchi, Takeo
Format: Article
Language:English
Subjects:
Alcohols
Alkylaluminium
Alkylation
Carboxylic acids
Catalysis
Conversion
Copper
Derivatives
Difluorohomoallyl alcohol
Dipeptide isostere
Fluoroalkene
Grignard reagent
Indium
Overman rearrangement
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Summary:[Display omitted] ► High yield and highly Z selective allylic alkylation reaction of difluorohomoally alcohol derivatives with Grignard reagents and CuI catalyst leading to fluoroallyl alcohol derivatives. ► Complete 1,3-chirality transfer in the imidate Claisen rearrangement of the above fluoroallyl alcohol derivatives. ► A convienient method for the preparation of ( Z)-fluoroalkene dipeptide isosteres in optically pure form. Difluoroallylation of optically pure O-silylated ( S)-2-methyl-3-hydroxypropanal 10a with bromodifluoropropene mediated by indium provided the corresponding difluorohomoallyl alcohol 11a with low diastereoselectivity, but without a decrease in optical purity. Defluorinative allylic alkylation of each diastereomer of the difluorohomoallyl alcohol efficiently proceeded by the reaction with trialkylaluminium and Cu(I) system or Grignard reagent and a catalytic amount of CuI system in THF to give the fluorine-substituted allylic alcohol 12 in an high yield and in an excellent Z selective manner. Subsequent imidate Claisen rearrangement of the allylic alcohol 12 proceeded with a complete 1,3-chirality transfer to give the fluoroalkene dipeptide isostere structure 14 after the final conversion of the primary alcohol 20 into the carboxylic acid form.
ISSN:0022-1139
1873-3328
DOI:10.1016/j.jfluchem.2011.03.007