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

• Published in: European Journal of Organic Chemistry 2011-01, Vol.2011 (2), p.355-363
• Main Authors: Husstedt, Wibke S., Wiehle, Susanne, Stillig, Christian, Bergander, Klaus, Grimme, Stefan, Haufe, Günter
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; Chemistry; Conformation analysis; Enantioselectivity; Exact sciences and technology; Fluorohydrins; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Nucleophilic substitution; Organic chemistry; Organofluorine chemistry; Preparations and properties; Quantum chemical calculations
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201001224

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. Thestereochemical 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. Regio‐ and stereoselective ring opening of enantio‐pure epoxides or cyclic sulfates with pyridine·9HF or TBAF delivers anti‐ or syn‐configurated 3‐fluoro‐2‐hydroxy‐ or 2‐fluoro‐3‐hydroxyalkanoates, respectively. The relative energies of conformers were calculated by quantum chemical methods. Those of 3‐fluoro‐2‐hydroxy isomers are influenced by intramolecular O–H···O=C hydrogen bonds, while the regioisomers show close O–H···F–C contacts.