Conformational behaviour of methyl 2-fluoroesters through theoretical calculations, NMR and IR spectroscopy

Abstract

The conformational equilibrium of methyl 2-fluoropropionate (1) was studied through a combination of NMR, theoretical calculations and solvation theory. IR spectroscopy was used as an auxiliary technique for this analysis. The ¹J_CF couplings were analysed using theoretical and solvation calculations to give conformer energies in the solvents studied, vapour phase energies, and also the coupling constants for the distinct rotamers. The trans rotamer is more stable than the cis rotamer in the vapour phase by 0.4 kcal mol⁻¹ and the conformers are of equal energy in CCl₄. The more polar cis form is the major rotamer in the remaining solvents studied. Theoretical evaluation at the B3LYP/6-311++g(d,p) level for the α-alkyl substituent effect was carried out using methyl 2-fluorobutyrate (2), methyl 2-fluoro-tert-butylacetate (3) and methyl 2-fluorophenylacetate (4) as models, and showed the great effect of these substituents on the conformational stabilities. The governing interactions of these systems were rationalised in terms of both classical and non-classical effects, such as steric, electrostatic, O⋯H–C hydrogen bonding, gauche effect and hyperconjugative interactions.