To achieve the envisioned metallocavitand architecture, a suitable macrocyclic precursor with the appropriately positioned modifiable groups was required. Such a compound was prepared by an acid-catalyzed condensation of 3,5dimethoxyphenol and paraformaldehyde (Scheme 1), similarly to the reported calix [4]-and calix [5]tetrolarenes. The resulting novel macrocycle 1, which we suggest to name triol [4]arene, can be considered a hybrid between a calix [4]arene and a resorcin [4]arene, as it features oxygenbased functionalities on both lower and upper rims. While the lower rim contains free hydroxyl groups, those located at the upper rim are protected as methyl ethers -enabling an orthogonal functionalization of each rim. In the crystal phase this macrocycle adopts a pinched-cone conformation (Fig. ) which is stabilized by four intramolecular H-bonds between the lower-rim hydroxyls, as typical for calix [4]arenes. Next, following a method originally developed for the 1,3derivatization of p-t Bu-calix [4]arene, the two distal hydroxyl groups at the lower rim of 1 were converted into the primary amino functionalities via intermediates 2 and 3 (the latter being a mixture of two atropisomers A and B, see SI) (Scheme 1 and Fig. ). The subsequent annulation of the resulting diamino derivative 4 to form a rigid penta-coordinate cage required a bridging unit of an appropriate size and bite angle. Previous reports of analogous trans-annular bridges in calix [4]-and calix [6]arenes were limited to long-chain polyethers, which form large flexible loops unsuitable for transition metal binding. On the contrary, employing shorter and more rigid linkers (e.g., 1,1'-di(acyl)metallocenes) resulted in only dimeric and trimeric products. To identify the best candidate for the bridging unit, we performed a set of preliminary density functional theory (DFT) calculations, considering possible condensation products of 4 with three representative bis-aldehyde-functionalized heterocycles. The candidates chosen vary widely in their bite angles (see Scheme S1 and the explanations therein). While these hypothetical reactions were predicted to be endothermic, our calculations revealed a clear preference of this system for the dibenzofuran derivative 5*DBF, which provides a bite angle of ~90° (∆E = +16.0 kcal/mole) over the pyridine and xanthene counterparts, 5*Pyr and 5*Xant, with the bite angles of ~0° and ~120° (∆E = +31.2 and 31.6 kcal/mol), respectively. Based on these findings, we reacted compound 4 with a previously reported 2,8-dibutyl-functionalized dibenzofuran-4,6-dicarbaldehyde, resulting in the formation of a monomeric diimine 5, as the sole product (Scheme 1). Presence of the n-butyl tails in the former bisaldehyde was crucial for ensuring an adequate solubility of the diimine product. Having thus completed the construction of a metal-binding cage at the lower rim of the designed cavitand, we proceeded with building its aromatic walls at the upper rim. This was achieved by a complete demethylation of 5 to obtain the deca-hydroxy derivative 6, followed by an etherification with four equivalents of 2,3-dichloroquinoxaline -each reacting with a pair of adjacent hydroxyl groups, in accordance with the established protocols (Scheme 1). Scheme 1. Synthesis of the cavitand ligand framework. The final cavitand product 7 was obtained in a moderate yield (45% from 6), as a white powder. In the solid state, this compound adopts a vase conformation (Fig. ), similar to that previously observed by Cram and Rebek, with disordered DCM molecules (not shown) occupying its molecular cavity. This semi-rigid structure, reinforced by two intramolecular H-bonds between the imine nitrogens and the phenolic protons, effectively pre-organizes the coordination cage for metal complexation.