Unveiling the “Booster Effect” of Fluorinated Alcohol Solvents: Aggregation-Induced Conformational Changes and Cooperatively Enhanced H-Bonding

The influence of conformation and aggregation on the hydrogen bond donor ability of fluorinated
alcohol solvents [1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 1-phenyl-2,2,2-trifluoroethanol (PhTFE)] was
explored theoretically (DFT) and experimentally (NMR, kinetics, crystal structure analyses). The detailed
DFT analysis revealed a pronounced dependence of the H-bond donor ability on the conformation along
the CO-bond of the monomeric alcohols. The donor orbital energy (σ*OH) decreases and the molecular
dipole moment (μ) increases drastically from the antiperiplanar (ap) to the synperiplanar (sp) HCCOH
conformation. The kinetics of olefin epoxidation with H2O2 in HFIP indicate higher order solvent aggregates
(2−3 monomers) to be responsible for the activation of the oxidant. Single-crystal X-ray analyses of HFIP
and PhTFE confirmed the existence of H-bonded aggregates (infinite helices, ribbons, and cyclic oligomers)
and the predominance of sc to sp conformations of the fluoroalcohol monomers. These aggregate structures
served as the basis for a DFT analysis of the H-bond donor ability at the terminal hydroxyl group of HFIP
mono- to pentamers. Both the LUMO energy and the natural charge of the terminal hydroxyl proton indicated
a substantial cooperative influence of dimerization and trimerization on the H-bond donor ability. We therefore
conclude that dimers and trimers, with the individual monomers in their sc to sp conformation, play a crucial
role for the solvolytic and catalytic effects exerted by HFIP, rather than monomers.