A practical synthesis of cambiarenes with mechanistic insights

Macrocyclic systems with supramolecular applications possess broad utility, yet their impact is often limited by the practicality of their syntheses. A tetrameric macrocycle capable of reversible redox switching, a class of molecules that we have termed ‘cambiarenes,’ was previously obtained in good yield but required an expensive and moisture-sensitive reagent, restricting accessibility. In this work, we report practical conditions for the synthesis of this cambiarene using inexpensive, commercially available starting materials under mild conditions. Mechanistic investigations indicated that the cambiarene predominantly forms via oligomerization followed by intramolecular backbiting, with evidence that this pathway is kinetically accessible and leads to a locally stabilised macrocyclic product under the conditions examined. These insights provide a foundation for more widespread use of cambiarenes in supramolecular applications and highlight how practical synthetic considerations could accelerate the adoption of functional macrocyclic hosts.