Copper mediated defluorinative allylic alkylation of difluorohomoallyl alcohol derivatives directed to an efficient synthetic method for (Z)-fluoroalkene dipeptide isosteres |
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Authors: | Daisuke Watanabe Akio Saito Hikaru Yanai Yuko Nakamura Azusa Sato |
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Institution: | a School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan b Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan |
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Abstract: | 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. |
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Keywords: | Fluoroalkene Difluorohomoallyl alcohol Alkylaluminium Grignard reagent Overman rearrangement Dipeptide isostere |
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