Synthesis and Preferred Conformations of All Regio- and Diastereoisomeric Methyl 2,3-Fluorohydroxyalkanoates

Selective syntheses of enantiopure regio- and diastereomeric methyl 2,3-fluoro-hydroxyalkanoates via four different routes employing two types of fluorination reagents are reported. The anti- and syn-3-fluoro-2-hydroxyalkanoates 1 and 3 were prepared by treating the corresponding epoxides with Olah's reagent (Py.9HF). Cyclic sulfates prepared from the enantiomeric diols were ring-opened with TBAF to give the anti- and syn-2-fluoro-3-hydroxyalkanoates 2 and 4. The stereochemical analysis was performed mainly by NMR spectroscopy. Applying DFT/B3LYP and SCS-MP2 quantum chemical methods, the coupling constants and relative energies of conformers were calculated. Solvent effects were considered using the COSMO continuum model.