Facile synthesis of 4-deoxy-4-fluoro-α-d-talopyranoside, 4-deoxy-4-fluoro-α-d-idopyranoside and 2,4-dideoxy-2,4-difluoro-α-d-talopyranoside

The title compounds were prepared by two independent syntheses using inexpensive commercially available starting materials. 4-Deoxy-4-fluoro-α-d-talopyranoside served as a precursor to 4-deoxy-4-fluoro-α-d-idopyranoside, allowing for inversion of configuration at C-3 via a three-step protocol. The synthesis of 2,4-dideoxy-2,4-difluoro-α-d-talopyranoside is based on two nucleophilic fluorination events at C-2 then at C-4 using TBAF·3H2O and TBAF·4tBuOH as a fluoride source. All compounds are prepared as pure stereoisomers and are therefore suitable probes for OH⋯F H-bonding studies by 1H NMR spectroscopy.

Graphical abstract4-Deoxy-4-fluoro-α-d-idopyranosides and 2,4-dideoxy-2,4-difluoro-α-d-talopyranosides were prepared in two independent syntheses, in good yields from commercially available starting materials.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel methyl 4-deoxy-4-fluoro-6-O-trityl-α-d-idopyranoside was accessed in 3 steps in 25% overall yield from a readily available precursor. ► Fluorination of 2-O-Tf-α-d-glucopyranoside with TBAF·3H2O in tBuOH gave 2-fluoro-α-d-mannopyranoside in a vastly improved yield of 77%. ► The novel methyl 2,4-dideoxy-2,4-difluoro-6-O-pivaloyl-α-d-talopyranoside was synthesized in 7 steps with an overall yield of 22%. ► The target compounds presented in this paper can be regarded as ideal probes for the study of intramolecular OH⋯F H-bonds by 1H NMR spectroscopy.