Fluorinated Carbohydrates. 2. Selective Fluorination of Gluco- and Mannopyranosides. Use of 2-D NMR for Structural Assignments

Article abstract of DOI:10.1021/jo00172a054

Methyl and phenyl α-glucosides, or suitably protected derivatives, may be selectively fluorinated with (diethylamino)sulfur trifluoride (DAST) at the 4- or 6-position to afford the corresponding fluorinated galacto- or glucopyranoside.In contrast to the α-glucosides, the β-glucosides underwent ring fluorination at C-3 to give the 3-deoxy-3-fluoro-β-allo derivatives.High yields of primary fluorinated (C-6) products were obtained from both α- and β glucosides by use of appropriate reaction times.Use of 6-O-trityl derivatives of methyl α- and β-glucosides gave methyl 4-deoxy-4-fluoro-α-galactopyranoside (22) and methyl 3-deoxy-3-fluoro-β-allopyranoside (19), respectively.Use of 2-D NMR (COSY) for structural assignements is also described.Fluorinated p-nitrophenyl α- and β-gluco- and -galactopyranosides (such as 15) have also been prepared by the above DAST reactions. 6-O-Pivaloate esters of methyl α-gluco-and α- and β-galactopyranoside have been prepared as an acid and DAST-stable 6-O protecting group.Proof of an intramolecular fluoride-ion delivery mechanism for the S_N2 displacement reaction at C-4 in methyl α-D-mannopyranoside is described.Methyl 4-amino-4,6-dideoxy-6-fluoro-α-D-glucopyranoside, methyl 6-amino-3,6-dideoxy-3-fluoro-β-D-allopyranoside, and methyl 6-amino-4,6-dideoxy-4-fluoro-α-D-talopyranoside were also prepared via the above methodology.