Fluorine labeling of ortho-phenylenes to facilitate conformational analysis

¹H NMR spectroscopy is a powerful tool for the conformational analysis of ortho-phenylene foldamers in solution. However, as o-phenylenes are integrated into ever-more-complex systems, we are reaching the limits of what can be analyzed by ¹H- and ¹³C-based NMR techniques. Here, we explore fluorine labeling of o-phenylene oligomers for analysis by ¹⁹F NMR spectroscopy. Two series of fluorinated oligomers have been synthesized. Optimization of monomers for Suzuki coupling enables an efficient stepwise oligomer synthesis. The oligomers all adopt well-folded geometries in solution, as determined by ¹H NMR spectroscopy and X-ray crystallography. ¹⁹F NMR experiments complement these methods well. The resolved singlets of one-dimensional ¹⁹F{¹H} spectra are very useful for determining relative conformer populations. The additional information from two-dimensional ¹⁹F NMR spectra is also clearly valuable when making ¹H assignments. Comparison of ¹⁹F isotropic shielding predictions to experimental chemical shifts is not, however, currently sufficient by itself to establish o-phenylene geometries.