Size‐Control by Anion Templating in Mechanochemical Synthesis of Hemicucurbiturils in the Solid State

Abstract

Self‐organization is one of the most intriguing phenomena of chemical matter. While the self‐assembly of macrocycles and cages in dilute solutions has been extensively studied, it remains poorly understood in solvent‐free environments. Provided here is the first example of using anionic templates to achieve selective assembly of differently‐sized macrocycles in a solvent‐free system. Using acid‐catalyzed synthesis of cyclohexanohemicucurbiturils as a model, size‐controlled, quantitative synthesis of 6‐ or 8‐membered macrocycles by spontaneous anion‐directed reorganization of mechanochemically‐made oligomers in the solid state is demonstrated.

Rapid Mechanochemical Synthesis of Amides with Uronium-Based Coupling Reagents, a Method for Hexa-amidation of Biotin[6]uril

“…Implementation of the two objectives mentioned above was required as a prerequisite for the third objective as our ultimate goal. Due to the interest of our group in the synthesis and supramolecular applications of macrocyclic host molecules, [38][39][40][41][42][43] we required a robust procedure for amide-functionalization of biotin [6]uril macrocycle (1), [44][45][46] to access the family of modified biotin [6]uril hosts. Despite the apparent ease of such a transformation, it also presented a substantial challenge: six-fold stepwise amidation of carboxylate groups in 1 is inevitably accompanied by accumulation of the "failed" underfunctionalized products if incomplete coupling occurs at each step.…”

“…Amide Coupling of Biotin [6]uril. As a part of our ongoing efforts towards the development of new chiral supramolecular receptors, [38][39][40][41][42][43] we needed an expedient synthetic procedure for derivatization of biotin [6]uril (1), 44 easily available in multigram quantities by HCl-catalyzed condensation of formaldehyde with D-biotin. The starting macrocyclic molecule, notable for its anion binding properties, common for the cucurbituril family, [73][74][75][76][77] satisfies 6 carboxylic functions, which could be conveniently coupled with various amines, thus providing facile access to a library of diversely functionalized chiral macrocyclic receptors.…”