Mechanism of the conversion of inverted CB[6] to CB[6

Inverted cucurbitn]urils (iCBn]) form as intermediates during the synthesis of cucurbitn]urils from glycoluril and formaldehyde in HCl (85 degrees C). Product resubmission experiments establish that the diastereomeric iCB6] and iCB7] are kinetic products that are less stable thermodynamically than CB6] or CB7] (>2.8 kcal mol(-1)). When iCB6] or iCB7] is heated under aqueous acidic conditions, a preference for ring contraction is noted in the formation of CB5] and CB6], respectively. Interestingly, under anhydrous acidic conditions ring size is preserved with iCB6] delivering CB6] cleanly. To establish the intramolecular nature of the iCB6] to CB6] conversion under anhydrous, but not aqueous, acidic conditions we performed crossover experiments involving mixtures of iCB6] and its (13)C=O labeled isotopomer (13)C(12)-iCB6]. An unusual diastereomeric CB6] with a M?bius geometry (13) is proposed as a mechanistic intermediate in the conversion of iCB6] to CB6] under anhydrous acidic conditions. The improved mechanistic understanding provided by this study suggests improved routes to CBn]-type compounds.