Methylene-bridged glycoluril dimers

Witt, D. Lagona, J. Damkaci, F Fettinger, J. C. Isaacs, L. Diastereoselective formation of methylene-bridged glycoluril dimers. Org. Lett. 2000, 2,755-758. 

Although none of the applications of the CB[n] family described in Section 4.3 were known in 1998 when we began our work in the area, they provide post-facto support for our assertion that a firm knowledge of the mechanism of CB[n] formation would be important. This section describes our work with S- and C-shaped methylene-bridged glycoluril dimers that provided insight into the early steps of the mechanism of CB[n] formation. 

S-shaped and C-shaped Methylene-bridged Glycoluril Dimers... 

The high level of complexity of the CB[n] -forming reaction led us to initially study S-shaped and C-shaped methylene-bridged glycoluril dimers (11C and 11S, Scheme 4.3). This section details the lessons learned from those model studies. 

Scheme 4.12 Synthesis of S- and C-shaped methylene-bridged glycoluril dimers. R — C02Et. Conditions (a) PTSA, (CH20)n, CICH2CH2CI, reflux (b) PTSA, CICH2CH2CI, reflux (n.d. = not detected).

FROM METHYLENE BRIDGED GLYCOLURIL DIMERS TO CUCURBITINIURIL ANALOGS WITH SOME DETOURS ALONG THE WAY... 

SCHEME 5. The first C-shaped methylene bridged glycoluril dimer. R = CO Et. 

As suggested by the retrosynthetic analysis (Scheme 4) described above, there are three pathways to methylene bridged glycoluril dimers -namely - 1) two equivalents of glycoluril cyclic ether (e.g. 12), 2) two equivalents of glycoluril NH compound (e.g. 13) with added... 

Given the high level of diastereoselectivity observed in the complexation behavior of 70a and ( )-71, we wondered what would happen if we created mixtures of these methylene bridged glycoluril dimers. Would a mixture of 70a and ( )-71, for example, form a mixture of 70a 70a and (+)-71 H-71, or would heteromeric crossover aggregates (e.g. 70a (+)-71) also be formed Figure 3 shows the H NMR spectra recorded for an equimolar mixture of 70a and ( )-71 in CDCI3. 

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