Fluorine labeling of ortho-phenylenes to facilitate conformational analysis

Viraj C. Kirinda, Gopi Nath Vemuri, Nicholas G. Kress, Kaitlyn M. Flynn, Nuwanthika Dilrukshi Kumarage, Briana R. Schrage, David L. Tierney, Christopher J. Ziegler, and C. Scott Hartley*
J. Org. Chem. 2021, 86, 15085–15095
[Published version | NSF-PAR | Preprint | Raw data]


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. The comparison of 19F isotropic shielding predictions to experimental chemical shifts is not, however, currently sufficient by itself to establish o-phenylene geometries.