Cyclodextrins aldol condensations

Enolization can be part of an aldol condensation. We examined the aldol cyclization of compound 52 to 53 catalyzed by the bis-imidazole cyclodextrin artificial enzymes, and again saw that the A,D isomer was the preferred catalyst [139]. This was not an obvious result the rate-limiting step in this case is cyclization of the enol, which is... 

Cyclodextrins with two imidazole groups on the primary hydroxyl side can enhance the enolate formation [86] of a simple bound ketone by bifunctional acid-base catalysis and accelerating the intramolecular aldol condensation of bound ketoaldehyde and dialdehyde. The aldolase mimics which catalyzed crossed aldol condensations were obtained by the assembly of (i-CD and various amino moieties as Schiff base [87]. 

We prepared a series of eatalysts with relatively simple groups attached to a cyclodextrin that would be able to catalyse an aldol condensation between acetone and some bound aromatic aldehydes, when the acetone formed an enamine with a catalytic group such as a simple amine. We observed catalyses as high as 270-fold relative to the uncatalysed aldol condensation with some of these cyclodextrin derivatives. 

We also examined aldol condensations of the dialdehyde 17. Without the special catalysis afforded by the cyclodextrin i w-imidazoles there was an almost random reaction to form compounds 18 and 19, as either aldehyde acted as the enofizing group. However, the cyclodextrin imidazole catalysts directed the selective formation of products 19, with no selectivity among its stereoisomers. Interestingly, the least selective catalyst for 17 was the cyclodextrin mono-imidazole, the AD isomer of the fcw-imidazole was more selective, and the most selective was the AB isomer. Obviously these results indicate that the cyclodextrin imidazole catalysts promote enolization of the aldehyde group closest to the cyclodextrin, as expected, but the subtlety of preferences among the bw-imidazole isomers is not yet understood in this case. 

D.-Q. Yuan, S. D. Dong, R. Breslow, Cyclodextrin-based class I aldolase enzyme mimics to catalyse crossed aldol condensations, Tetrahedron Lett., 1998, 39, 7673-7676. 

Desper, JM and R Breslow (1994). Catalysis of an intramolecular aldol condensation by imidazole-bearing cyclodextrins. Journal of the American Chemical Society, 116(26), 12081-12082. 

Watanabe, K.-L Yamada, Y. Goto, K. (1985) New type aldol condensations catalyzed by metal(ll) complexes of a-amino acid esters and that with cyclodextrin systems. Bull. Chem. Soc. Jpn, 58,1401-6. 

Zhang, Y. Xu, W. (1989) The aldol condensation catalyzed by metal-(ll)-p-cyclodextrin complexes, Synth. Commun., 19,1291-6. 

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