New approach to synthesize β,β-difluorohomoallylic alcohols

Treatment of ethyl 4,4-difluoro-3-(triethylsilyl)but-3-enoate (3) with TBAF in the presence of MS4Å followed by addition of an aromatic aldehyde afforded ethyl (E)-4,4-difluoro-5-hydroxy-5-arylpent-2-enoate (1) that was a versatile intermediate for constructing a stable isostere of peptide or fluorinated sugar molecules. This strategy offers straightforward approach to synthesize such a versatile intermediate (1).

Figure optionsDownload as PowerPoint slideHighlights
► Ethyl 4,4-difluoro-3-(triethylsilyl)but-3-enoate (3) was synthesized.
► 3 generates 4,4-difluorocarbanion by treatment of 3 with TBAF.
► The generated 4,4-difluorocarbanion attacks to aldehydes.
► 3 serves good building block for constructing β,β-difluorohomoallylic alcohols.