Applications of 19F multidimensional NMR

Fluorine (19F) NMR spectra are invaluable in the analysis of fluorine containing compounds and 19F chemical shift correlations with structure have been used for over 40 years (for detailed reviews see Refs. [1-17]). Two-dimensional (2D) NMR techniques have been used for many years to analyze organic compounds containing 1H and 13C and numerous publications have described the techniques and theory [18-21]. Despite the high sensitivity and 100% abundance of 19F, the application of 2D 19F NMR methods to fluorochemicals is not as routine as those for 1H. Reasons for this include the wide dispersion of 19F chemical shifts, negating the need for 2D NMR and creating difficulties in uniform excitation of the entire 19F bandwidth, a narrow dispersion for 13C atoms attached to fluorine, specialized hardware requirements, and a lack of general knowledge about 19F coupling constants necessary for interpretation of the correlations. This manuscript reviews 19F 2D NMR techniques that have been described in the literature for spectra of fluorine containing compounds. Included in each section is a brief discussion of hardware requirements as well as values of 19F coupling constants to emphasize the differences in interpretation of spectra of fluorinated vs. non-fluorinated samples. Examples of each of the techniques applied to a variety of molecules are discussed to give a flavor of how they can be used; however, the review is not intended to exhaustively cover all published examples. In addition, the review will only cover solution state techniques and applications. While the focus of this review is on multidimensional techniques, there are some recent developments in one-dimensional multi-resonance techniques that will be briefly covered (e.g. 13C{19F/1H} decoupled 1D NMR spectra). Most 2D NMR experiments require uniform excitation over the entire bandwidth of observed resonances, otherwise major sensitivity losses and/or spectral artifacts may occur. Most 19F 2D applications to date have either analyzed compounds with fairly narrow chemical shift ranges or acquired multiple 2D spectra covering different regions of the 19F NMR spectrum. As a guide to general users, this review will discuss the robustness of each class of experiment to performance over wide bandwidths and the considerations that need to be made to ensure adequate performance. In addition, Section 5.3 will cover the limited number of publications that have described pulse sequence modifications to address wide bandwidth performance. The nomenclature used throughout the paper will refer to nuclei observed in 2D experiments as AX-BX, where AX is the detected nucleus and BX is the indirectly detected nucleus (i.e. 19F-13C HSQC for an inverse detected correlation experiment). In addition, AX{BX} or AX{BX,CX} refers to AX detected 1D experiments with BX and/or CX decoupling. © 2006 Elsevier B.V. All rights reserved.