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Keywords:

  • fluorine;
  • HOESY;
  • NMR spectroscopy;
  • nitrogen heterocycles;
  • stereoelectronic effects

Abstract

A series of 3-fluoropyrrolidines have been studied to investigate the influence of the stereoelectronic fluorine gauche effect on ring conformations in the solid state by single-crystal X-ray analysis and in solution phase by NMR spectroscopy. As part of these studies 1D 19F–1H heteronuclear NOE (HOESY) experiments have been optimised for applications to small molecules and are described in detail. These have been employed to estimate 19F–1H internuclear distances and were combined with vicinal 3J(F,H) and 3J(H,H) scalar coupling constants to analyse the ring conformations. Where possible the derived solution-phase structural data have been compared with those of the crystalline state. The results demonstrate the influence of the gauche effect in stabilising Cγ-exo conformations of the fluorinated pyrrolidines. It was further shown that when steric interactions were also present, this conformational bias was diminished and the contribution of the alternative Cγ-endo conformation was seen to increase in solution at lower sample temperatures.