Fluorine–proton correlation from isolated trifluoromethyl groups using unresolved J‐couplings

Abstract

Fluorine-containing compounds are rare in biological systems, so fluorine NMR spectroscopy can selectively detect and quantify fluorinated xenobiotics in crude biological extracts. The high sensitivity of fluorine NMR allows the detection of compounds containing isolated trifluoromethyl groups at nanogramme levels. However, it only provides limited structural information about trifluoromethyl-containing compounds owing to the difficulty of interpreting fluorine chemical shifts and the low sensitivity of HOESY experiments used to correlate fluorine nuclei with protons in the same compound. This paper demonstrates that long-range fluorine-proton J-couplings can be used to correlate isolated trifluoromethyl groups with nearby protons with significantly higher sensitivity than HOESY. Fluorine-observe fluorine-proton HMQC can even give correlations when the fluorine-proton J-couplings are less than the observed fluorine resonance linewidth, so it provides a useful alternative source of structural information about fluorinated xenobiotics.