Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Chemistry. 2012 Oct 8;18(41):13133-41. doi: 10.1002/chem.201201577. Epub 2012 Sep 18.
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.
我们研究了一系列 3-氟代吡咯烷，通过单晶 X 射线分析和溶液相 NMR 光谱研究立体电子氟 gauche 效应对固态中环构象的影响。作为这些研究的一部分，我们优化了一维 (19)F-(1)H 异核 NOE（HOESY）实验，以便应用于小分子，并详细描述了这些实验。这些实验用于估计 (19)F-(1)H 核间距离，并与相邻 (3)J(F,H) 和 (3)J(H,H) 标量耦合常数相结合，以分析环构象。在可能的情况下，将所得溶液相结构数据与晶体相进行了比较。结果表明 gauche 效应在稳定氟化吡咯烷的 C(γ)-exo 构象方面的影响。进一步表明，当存在空间位阻相互作用时，这种构象偏差减小，并且在较低的样品温度下，在溶液中观察到替代的 C(γ)-endo 构象的贡献增加。
