title: Conformational analysis of fluorinated pyrrolidines using 19F-1H scalar couplings and heteronuclear NOEs.
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 (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.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Lorraine E
authors.initials: LE
authors.lastname: Combettes
authors.forename: Philip
authors.initials: P
authors.lastname: Clausen-Thue
authors.forename: Michael A
authors.initials: MA
authors.lastname: King
authors.forename: Barbara
authors.initials: B
authors.lastname: Odell
authors.forename: Amber L
authors.initials: AL
authors.lastname: Thompson
authors.forename: Véronique
authors.initials: V
authors.lastname: Gouverneur
authors.forename: Tim D W
authors.initials: TD
authors.lastname: Claridge
mesh_terms: D018360:Crystallography, X-Ray; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry*
chemical_list: D005462:Fluorine Radioisotopes; D011759:Pyrrolidines; D012996:Solutions