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]

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