Balancing on a Knife’s Edge: Studies on the Synthesis of Pillar[6]arene Derivatives

Abstract

Pillar­[6]­arenes are established as crucial building blocks in supramolecular chemistry; however, they can be difficult to synthesize, particularly in the absence of large solubilizing substituents. In this work, we explore variability in literature syntheses of pillar[6]­arene derivatives and suggest that the outcome is dependent on whether oligomeric intermediates stay in solution long enough for the thermodynamically favorable macrocyclization to occur. We demonstrate that in a previously capricious BF3·OEt2-mediated procedure, ≤5 mol % of a Brønsted acid can slow down the reaction to favor macrocycle formation.

Stereoselective Single Step Cyclization to Give Belt-Functionalized Pillar[6]arenes

“…It is interesting that although all reaction components stay soluble, and thus there is no loss of equilibrium due to precipitation, yields are low, and we attribute this to the sheer unlikeliness of forming significant amounts of the acyclic hexamer with the right arrangement of methyl groups. Attempts to leave the reactions for longer to increase yields were unsuccessful, presumably due to irreversible side-reactions eventually degrading the macrocycle.…”

“…Macrocyclization yields were relatively low. This does not result from precipitation of oligomeric/polymeric material, 51 but instead may result from difficulties in the intermediate oligomer reaching the necessary rtctct configuration to allow cyclization. While the Friedel−Crafts reactions required to build up the oligomer are known to be reversible, 52 which will presumably allow for conversion between isomers, the statistical improbability of achieving this isomer presumably accounts for the low yield and long reaction times.…”

Triphenylamine[3]arenes: Streamlining Synthesis of a Versatile Macrocyclic Platform for Supramolecular Architectures and Functionalities

“…While pillar [5]arenes can be synthesized readily in high yields from commercially available materials via facile onepot reactions, the synthesis of pillar [6]arene -first achieved by Meier and Cao [8b] -has proven to be capricious, heavily contingent upon specific conditions and substituents (Figure 1a). [10] Recent advancements in synthetic protocols for pillar [6]arenes, reported independently by White [10] and by Hof, [11] have shown promise in enhancing the accessibility of pillar [6]arenes. Furthermore, assorted pillar [6]arene variants have been designed and synthesized, spearheaded by various research groups, paving the way for crafting symmetryreduced or bridge-functionalized pillar [6]arene derivatives.…”