Diastereoselective formation of glycoluril dimers:: Isomerization mechanism and implications for cucurbit[n]uril synthesis

被引:80
作者
Chakraborty, A
Xu, AX
Witt, D
Lagona, J
Fettinger, JC
Isaacs, L [1 ]
机构
[1] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA
[2] Lanzhou Univ, Natl Lab Appl Organ Chem, Lanzhou 730000, Peoples R China
关键词
D O I
10.1021/ja025876f
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Cucurbit[6]uril (CB[6]) is a macrocyclic compound, prepared in one pot from glycoluril and formaldehyde, whose molecular recognition properties have made it the object of intense study. Studies of the mechanism of CB[n] formation, which might provide insights that allow the tailor-made synthesis of CB[n] homologues and derivatives, have been hampered by the complex structure of CB[n]. By reducing the complexity of the reaction to the formation of S-shaped (12S-18S) and C-shaped (12C-18C) methylene bridged glycoluril dimers, we have been able to probe the fundamental steps of the mechanism of CB[n] synthesis to a level that has not been possible previously. For example, we present strong evidence that the mechanism of CB[n] synthesis proceeds via the intermediacy of both S-shaped and C-shaped dimers. The first experimental determination of the relative free energies of the S-shaped and C-shaped dinners indicates a thermodynamic preference (1.55-3.25 kcal mol(-1)) for the C-shaped diastereomer. This thermodynamic preference is not because of self-association, solvation, or template effects. Furthermore, labeling experiments have allowed us to elucidate the mechanism of this acid-catalyzed equilibrium between the S-shaped and C-shaped diastereomers. The equilibration is an intramolecular process that proceeds with high diastereoselectivity and retention of configuration. On the basis of the broad implications of these results for CB[n] synthesis, we suggest new synthetic strategies that may allow for the improved preparation of CB[n] (n > 8) and CB[n] derivatives from functionalized glycolurils.
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页码:8297 / 8306
页数:10
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