Determining the Enantiomeric Excess and Absolute Configuration of In Situ Fluorine-Labeled Amines and Alcohols by 19 F NMR Spectroscopy.

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 19 F nuclear magnetic resonance (NMR)-based analytical protocol for determining the enantiomeric excess and absolute configuration of in situ 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 19 F{ 1 H} NMR spectra. The measured Δδ RS signs were unambiguously used to correlate the absolute configurations of amines, amino alcohols, and alcohols. Moreover, the structure-dependent 19 F{ 1 H} NMR signals enabled absolute configuration determination by analyzing the relative chemical shifts of enantiopure analyte samples with [Co]BArF and ent -[Co]BArF.