Tiara[5]arenes (T[5]s), a new class of five‐fold symmetric oligophenolic macrocycles that are not accessible from the addition of formaldehyde to phenol, were synthesized for the first time. These pillar[5]arene‐derived structures display both unique conformational freedom, differing from that of pillararenes, with a rich blend of solid‐state conformations and excellent host–guest interactions in solution. Finally we show how this novel macrocyclic scaffold can be functionalized in a variety of ways and used as functional crystalline materials to distinguish uniquely between benzene and cyclohexane.

The synthesis of “rim-differentiated” C₅-symmetric pillar[5]arenes, whose two rims are decorated with different chemical functionalities, has remained a challenging task. This is due to the inherent statistical nature of the cyclization of 1,4-disubstituted alkoxybenzenes with different substituents, which leads to four constitutional isomers with only 1/16th being rim-differentiated. Herein, we report a “preoriented” synthetic protocol based on FeCl₃-catalyzed cyclization of asymmetrically substituted 2,5-dialkoxybenzyl alcohols. This yields an unprecedented 55% selectivity of the C₅-symmetric tiara-like pillar[5]arene isomer among four constitutional isomers. Based on this new method, a series of functionalizable tiara-pillar[5]arene derivatives with C₅-symmetry was successfully synthesized, isolated, and fully characterized in the solid state.