Fluorine Labeling of ortho -Phenylenes to Facilitate Conformational Analysis.

¹ H 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 ¹ H- and ¹³ C-based NMR techniques. Here, we explore fluorine labeling of o -phenylene oligomers for analysis by ¹⁹ F 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 ¹ H NMR spectroscopy and X-ray crystallography. ¹⁹ F NMR experiments complement these methods well. The resolved singlets of one-dimensional ¹⁹ F{ ¹ H} spectra are very useful for determining relative conformer populations. The additional information from two-dimensional ¹⁹ F NMR spectra is also clearly valuable when making ¹ H assignments. The comparison of ¹⁹ F isotropic shielding predictions to experimental chemical shifts is not, however, currently sufficient by itself to establish o -phenylene geometries.