Department of Chemistry, Korea Advanced Instituted of Science and Technology (KAIST), Daejeon 34141, Korea.
Anal Chem. 2022 Jan 18;94(2):1441-1446. doi: 10.1021/acs.analchem.1c04834. Epub 2021 Dec 23.
The determination of the enantiomeric excess and absolute configuration of chiral compounds is indispensable in synthetic, pharmaceutical, and biological chemistry. In this article, we describe an efficient F nuclear magnetic resonance (NMR)-based analytical protocol for determining the enantiomeric excess and absolute configuration of fluorine-labeled amines and alcohols. 2-Fluorobenzoylation was used to convert analytes to fluorinated amides or esters. The resulting F-labeled analytes were mixed with a cationic cobalt(III) complex, [Co]BArF, resulting in clean baseline peak separations of analyte enantiomers in F{H} NMR spectra. The measured Δδ signs were unambiguously used to correlate the absolute configurations of amines, amino alcohols, and alcohols. Moreover, the structure-dependent F{H} NMR signals enabled absolute configuration determination by analyzing the relative chemical shifts of enantiopure analyte samples with [Co]BArF and -[Co]BArF.
在合成、制药和生物化学中，对手性化合物的对映体过量和绝对构型的确定是必不可少的。在本文中，我们描述了一种基于 F 核磁共振（NMR）的高效分析方案，用于确定氟标记的胺和醇的对映体过量和绝对构型。2-氟苯甲酰化用于将分析物转化为氟化酰胺或酯。所得的 F 标记的分析物与阳离子钴（III）配合物[Co]BArF 混合，在 F{H}NMR 光谱中导致分析物对映体的干净基线峰分离。测量的Δδ符号可用于明确关联胺、氨基醇和醇的绝对构型。此外，结构相关的 F{H}NMR 信号通过分析与[Co]BArF 和-[Co]BArF 混合的对映纯分析物样品的相对化学位移来实现绝对构型的确定。
