Mechanism of the Conversion of Inverted CB[6] to CB[6]

Inverted cucurbit[n]urils (iCB[n]) form as intermediates during the synthesis of cucurbit[n]urils from
glycoluril and formaldehyde in HCl (85 °C). Product resubmission experiments establish that the
diastereomeric iCB[6] and iCB[7] are kinetic products that are less stable thermodynamically than
CB[6] or CB[7] (>2.8 kcal mol-1). When iCB[6] or iCB[7] is heated under aqueous acidic conditions,
a preference for ring contraction is noted in the formation of CB[5] and CB[6], respectively. Interestingly,
under anhydrous acidic conditions ring size is preserved with iCB[6] delivering CB[6] cleanly. To establish
the intramolecular nature of the iCB[6] to CB[6] conversion under anhydrous, but not aqueous, acidic
conditions we performed crossover experiments involving mixtures of iCB[6] and its 13CO labeled
isotopomer 13C12-iCB[6]. An unusual diastereomeric CB[6] with a Möbius geometry (13) is proposed as
a mechanistic intermediate in the conversion of iCB[6] to CB[6] under anhydrous acidic conditions. The
improved mechanistic understanding provided by this study suggests improved routes to CB[n]-type
compounds.