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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 (19)F-(1)H heteronuclear NOE (HOESY) experiments have been optimised for applications to small molecules and are described in detail. These have been employed to estimate (19)F-(1)H internuclear distances and were combined with vicinal (3)J(F,H) and (3)J(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 C(γ)-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 C(γ)-endo conformation was seen to increase in solution at lower sample temperatures.

Various 3-fluoropyrrolidines and 4-fluoropyrrolidin-2-ones were prepared by 5-exo-trig iodocyclisation from allylic fluorides bearing a pending nitrogen nucleophile. These bench-stable precursors were made accessible upon electrophilic fluorination of the corresponding allylsilanes. The presence of the allylic fluorine substituent induces syn-stereocontrol upon iodocyclisation with diastereomeric ratios ranging from 10:1 to > 20:1 for all N-tosyl-3-fluoropent-4-en-1-amines and amides. The sense and level of stereocontrol is strikingly similar to the corresponding iodocyclisation of structurally related allylic fluorides bearing pending oxygen nucleophiles. These results suggest that the syn selectivity observed upon ring closure involves I(2)-π complexes with the fluorine positioned inside.

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