Highly Selective Fluoride Recognition by a Small Tris-Urea Covalent Cage

A highly selective recognition of fluoride was achieved through the design of a small hemicryptophane cage (3) presenting a southern tris-urea hosting moiety. The resulting host–guest complex has been characterized by electrospray ionization-high-resolution mass spectrometry, 1H and 19F NMR, and X-ray diffraction techniques. In particular, X-ray diffraction analysis of [3·F–] reveals that the encapsulation of one fluoride, within 3, occurs through NH···F– H-bonding with the six NH residues of the tris-urea ligand. An association constant of 1200 M–1 was extracted from 1H NMR titration experiments, indicating that efficient fluoride binding also occurs in solution. Finally, in sharp contrast with previously reported urea-based hemicryptophane hosts, the small preorganized cavity found in 3 allows for an exclusive selectivity for fluoride over other competing halides.