Minimal Self-Immolative Probe for Multimodal Fluoride Detection

Two single-molecule, self-immolative fluoride probes, namely tert-butyldimethylsilyl-protected 2- and 4-difluoromethylphenol, are described. Compared to similar systems previously described, the probes are characterized by a simpler structure and straightforward, two-step preparation. Nevertheless, they allow the detection of fluoride ions at micromolar concentration by the naked eye, UV−vis absorption, and fluorescence. A detailed investigation of the self-immolative reaction reveals that the rate-limiting step is the release of the first fluoride ion from the difluoromethylphenolate intermediate. Moreover, the mutual position of the difluoromethyl- and tert-butyldimethylsilyl-protected residues has a relevant effect on the reactivity. Likely, a CF2H−O hydrogen bond in the 2-isomer increases the reactivity of the silyl ether toward hydrolytic cleavage but also stabilizes the phenolate intermediate, slowing the release of fluoride ions.