Synthesis of difluorinated β- and γ-amino acids: Investigation of a challenging deoxyfluorination reaction

Backbone-homologated amino acids containing the vicinal difluoride motif have been synthesised in a highly stereoselective manner. The key synthetic transformation is the DeoxoFluor®-mediated fluorination of a vicinal fluorohydrin. The synthetic route is amenable to the production of all possible stereoisomers of α,β-difluoro-γ-aminobutyric acid. In addition, a novel difluoromethyl-substituted β-amino acid is accessed via an unexpected rearrangement process.

Graphical abstractBackbone homologated amino acids containing vicinal-difluoro and geminal-difluoro motifs have been synthesised in a stereoselective manner.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Fluorinated β- and γ-amino acids have been synthesised. ► All possible stereoisomers can be selectively accessed. ► The key transformation is a modest-yielding deoxyfluorination of a vicinal fluorohydrin. ► Several fluorinating reagents were investigated including DeoxoFluor™, PBSF and XtalFluor-E®.