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.