Theoretical and X-ray Crystallographic Evidence of a Fluorine-Imine Gauche Effect: An Addendum to Dunathan’s Stereoelectronic Hypothesis

Abstract

The preference of β-fluoroimines to adopt a gauche conformation has been studied by single-crystal X-ray diffraction analysis and DFT methods. Empirical and theoretical evidence for a preferential gauche arrangement around the NCCF torsion angle (ϕ) is presented ((E)-2-fluoro-N-(4-nitrobenzylidene)ethanamine: ϕNCCF=70.0°). In the context of this study, the analysis of a pyridoxal-derived β-fluoroaldimine was performed, a species that is implicated in the inhibition of pyridoxal phosphate (PLP)-dependent enzymes by β-fluoroamine derivatives. The gauche preference of the internal aldimine (=NCH2CH2F) that can be rationalized by stereoelectronic arguments does not hold for the corresponding external system (NCHCH2F) (Emin when ϕNCCF=120°). Moreover, the CF bond is lengthened by more than 0.02 Å at ϕNCCF=±90°, when it is exactly antiperiplanar to the conjugated imine. This activation of the CF σ bond by an adjacent π system constitutes an addendum to Dunathan’s stereoelectronic hypothesis.