Istituto di Chimica Biomolecolare ICB, CNR, Sede secondaria di Sassari, Traversa La Crucca 3, Regione Baldinca, I-07100 Li Punti, Sassari, Italy.
CNR-SCITEC, Istituto di Scienze e Tecnologie Chimiche "Giulio Natta", sezione di via Golgi, via C. Golgi 19, 20133 Milano, Italy.
J Chromatogr A. 2022 Jun 21;1673:463097. doi: 10.1016/j.chroma.2022.463097. Epub 2022 Apr 30.
Planar chiral halogenated ferrocenes have come in useful as synthetic intermediates over the years, allowing for the preparation of functionalized derivatives for catalysis, material science, optoelectronics, and medicinal chemistry. Despite their chemical interest, few halogenated planar chiral ferrocenes have been prepared in enantiopure form by asymmetric synthesis so far. Enantioselective HPLC on polysaccharide-based chiral stationary phases (CSPs) has been used for resolving planar chiral ferrocenes making both enantiomers available. However, the enantioseparation of derivatives containing halogens or alkyl groups exclusively remains rather challenging. Given this context, in this study the enantioseparation of eleven dihalogenated planar chiral ferrocenes was systematically explored by using five polysaccharide-based CSPs under multimodal elution conditions. Baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.15 to 1.66. Thermodynamic quantities associated with the enantioseparations were derived from van't Hoff plots, and for 1-halo-2-(iodoethynyl)ferrocenes (1-halogen = F, Cl, Br) halogen-dependent thermodynamic profiles were identified on a cellulose tris(3,5-dimethylphenylcarbamate)-based column. The impact of CSP structure and mobile phase (MP) polarity on the enantioseparation was evaluated. In addition, with the aim to unravel the functions of halogen substituents in mechanisms and noncovalent interactions underlying selector-selectand complex formation at molecular level, local electron charge density of specific molecular regions of the interacting partners were evaluated in terms of calculated electrostatic potential (V) and related source function (SF) contributions. On this basis, the impact of halogen type and position on the enantioseparation was investigated by correlating theoretical and experimental data.
多年来，平面手性卤代二茂铁已被广泛用作合成中间体，可用于制备用于催化、材料科学、光电和药物化学的功能化衍生物。尽管它们具有化学意义，但到目前为止，通过不对称合成以对映纯形式制备的卤代平面手性二茂铁数量较少。多糖基手性固定相（CSP）上的对映选择性高效液相色谱法（HPLC）已用于拆分平面手性二茂铁，使两种对映体都可用。然而，对于含有卤素或烷基的衍生物的对映体分离仍然具有相当大的挑战性。鉴于此，在这项研究中，使用五种多糖基 CSP 在多模式洗脱条件下系统地探索了十一种二卤代平面手性二茂铁的对映体分离。对于九个分析物实现了基线对映体分离，分离因子（α）范围为 1.15 至 1.66。从 van't Hoff 图中得出了与对映体分离相关的热力学参数，对于 1-卤代-2-（碘代乙炔基）二茂铁（1-卤代物=F、Cl、Br），在基于纤维素三（3,5-二甲基苯基氨基甲酸酯）的柱上确定了与卤素相关的热力学曲线。评估了 CSP 结构和流动相（MP）极性对对映体分离的影响。此外，为了揭示卤代物取代基在分子水平上对选择剂-选择剂配合物形成的机制和非共价相互作用中的作用，根据计算静电势（V）和相关源函数（SF）贡献评估了相互作用伙伴特定分子区域的局部电子电荷密度。在此基础上，通过关联理论和实验数据，研究了卤代物类型和位置对对映体分离的影响。
