Fluorine labeling of ortho-phenylenes to facilitate conformational analysis

Abstract

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.

Conformational Control of ortho-Phenylenes by Terminal Amides

“…The fluoro groups were included to help with the NMR analysis, as we have previously shown that 19 F NMR chemical shifts are sensitive to o-phenylene backbone conformations and can be used to detect and quantify the folding populations of different conformers, complementing 1 H-and 13 C-based spectra. 36 The methoxy groups along the backbone were included to ensure solubility; they were not exchanged late in the synthesis for the acetoxy groups used for the imines (Chart 1a) because it was not found to be necessary to improve folding. The seven different oligomers with different amide groups in Chart 1b were synthesized as described in Scheme S3.…”