Molecular containers have attracted the interest of supramolecular chemists since the early beginnings of the field. Cavitands' inner cavities were quickly exploited by Cram and Warmuth to construct covalent containers able to stabilize and assist the characterization of short-lived reactive species such as cyclobutadiene or o-benzyne. Since then, more complex molecular architectures have been prepared able to store and isolate a myriad of fleeting species (i.e. organometallic compounds, cationic species, radical initiators…). In this review we cover selected examples of the stabilization of reactive species by encapsulation in molecular containers from the first reports of covalent containers described by Cram et al. to the most recent examples of containers with self-assembled structure (metal coordination cages and hydrogen bonded capsules). Finally, we briefly review examples reported by Rebek et al. in which elusive reaction intermediates could be detected in the inner cavities of self-folding resorcin[4]arene cavitands by the formation of covalent host-guest complexes. The utilization of encapsulated reactive species in catalysis or synthesis is not covered.

ABSTRACT:The synthesis, structural characterization and binding properties of two unprecedented multitopic receptors for ion-pair recognition are described. We isolated two of the six possible diastereomeric deep cavitand receptors resulting from the installation of four phosphonate groups at the upper rim of a calix[4]pyrrole-resorcin[4]arene hybrid scaffold. The isolated tetra-phosphonate receptors display either three (iooo) or four (oooo) of their P=O groups oriented away from the deep and functionalized aromatic cavity. In contrast to analogous tetra-phosphonate resorcin[4]arene cavitands, the fourteen-membered macrocyclic rings that contain the P=O groups in the tetraphosphonate calix[4]pyrrole cavitands are conformationally flexible, always adopting a conformation locating the phenyl substituents in equatorial position. The tetra-phosphonate calix[4]pyrroles exhibited larger affinity constants than the previously reported bis-phosphonate calix[4]pyrrole counterparts in the complexation of both tetramethylphosphonium and octylammonium chloride salts in non-polar solvents. We demonstrated that the iooo diastereoisomer was able to function as a multitopic receptor for organic chloride salts by switching the geometry of the 1:1 ion-paired complex from receptor-separated to close-contact depending on the quaternary or primary nature of the cobound organic cation. The ion-paired 1:1 complexes formed between the diastereomeric receptors and organic chloride salts were studied and thermodynamically characterized in solution. The determined stability constant values were compared with those obtained for the bis-phosphonate counterparts. The structure of the TMPCl7iooo complex was determined by X-ray structure and its formation was also evidenced in the gas phase.

A covalent molecular capsule based on reversible imine bonds and polar interior is prepared by the template-directed self-assembly of a tetraaldehyde calix[4]pyrrole scaffold with a diamine linker.

We report the synthesis, structural characterization, and binding properties of a series of unprecedented cavitands based on a meso-dodecyl-calix[4]pyrrole-resorcin[4]arene hybrid scaffold. The reported structural and conformational features of the prepared cavitands are derived from results obtained in solution, solid state, and molecular modeling studies. In the solid state, these cavitands are exclusively observed in the kite C4 structure and as a racemic mixture of two cyclochiral conformers, which are interconverting fast on the (1)H NMR time scale, according to solution studies. In agreement, molecular modeling studies assign an energy preference for the kite conformer of the cavitands. The polar interior of the synthesized containers allows for the inclusion of a series of pyridine N-oxide derivatives. This results in the formation of 1:1 complexes that are kinetically and thermodynamically highly stable. The putative switching process between the vase and kite forms of these cavitands is investigated in solution by means of variable temperature (1)H NMR experiments. N-Oxide guests that are size and shape complementary to the volume of the cavity of the vase form are also employed to facilitate its emergence. All of the results obtained indicate the existence of a remarkable preference toward the kite conformation both in free and bound calix[4]pyrrole-based cavitands.

A calix[4]pyrrole tetraurea, a polar guest and methyltrioctylammonium chloride quantitatively self-assemble in two different complexes in response to the components' stoichiometry.