Cucurbit[n]uril formation proceeds by step-growth cyclo-oligomerization

In contrast to the high yield formation of cucurbitn]uril (CBn]) from a 1:2 ratio of glycoluril to formaldehyde, the condensation of glycoluril with less than 2 equiv of formaldehyde delivers a reaction mixture that contains glycoluril oligomers (2-6) and CBn] compounds that lack one or more methylene bridges known as nor-seco-cucurbitn]urils (ns-CBn]). In this paper we report the chromatographic purification of C-shaped glycoluril oligomers (dimer-hexamer), their characterization in solution, and their X-ray crystal structures. Quite interestingly, despite being acyclic glycoluril pentamer 5 and hexamer 6 retain the ability to bind to guests typical of CB6] but are also able to expand their cavity to accommodate larger guests like cationic adamantane derivatives. We performed product resubmission experiments with glycoluril oligomers 2-6 and found preferences for the formation of specific ring sizes during CBn] formation. A comprehensive mechanistic scheme is proposed that accounts for the observed formation of 2-6 and ns-CBn]. Overall, the experiments establish that a step-growth cyclo-oligomerization process operates during CBn] formation.