Cyclodextrins benzoin condensation

When the thiazolium unit was attached to the larger y-cyclodextrin in 6, with eight glucose units in the ring, benzoin condensation of two benzaldehydes was indeed well... 

When fhe fhiazolium was affached to a y-CD, which is larger, characterized by eight glucose units, the benzoin condensation of two benzal-dehydes became possible. The rate was 150-fold higher than that obtained with a thiazolium salt lacking the cyclodextrin binding site (EM 150)... 

The use of thiazolium salts enables the benzoin condensation to proceed at room temperature. It can also be performed in dipolar aptotic solvents or under phase transfer conditions. Thiazolium salts such as vitamin Bi, thiazolium salts attached to y-cyclodextrin, macrobicyclic thiazolium salts, thiazolium carboxylate, ° naphtho[2,l-d]thiazolium and benzothiazolium salts catalyze the benzoin condensation and quaternary salts of 1-methylbenzimidazole and 4-(4-chlorophenyl)-4//-1,2,4-triazole are reported to have similar catalytic activity. Alkylation of 2-hydroxyethyl-4-methyl-l,3-thiazole with benzyl chloride, methyl iodide, ethyl bromide and 2-ethoxyethyl bromide yields useful salts for catalyzing 1,4-addition of aldehydes to activated double bonds. Insoluble polymer-supported thiazolium salts are catalysts for the benzoin condensation and for Michael addition of aldehydes. Electron rich al-kenes such as bis(l,3-dialkylimidazolidin-2-ylidenes) bearing primary alkyl substituents at the nitrogen atoms or bis(thiazolin-2-ylidene) bearing benzyl groups at the nitrogen atoms are examples of a new class of catalyst for the conversion of ArCHO into ArCHOHCOAr. 

Ikeda, H., Horimoto, Y., Nakata, M., Ueno, A. Artificial holoenzymes for benzoin condensation using thiazolio-appended -cyclodextrin dimers. Tetrahedron Lett. 2000, 41, 6483-6487. 

In early studies of this chemistry we had examined the ability of such thiazolium salts to catalyse the benzoin condensation, a process which also formally involves an acyl anion but which is really of course the anion in which the thiazolium salt has been added to the carbonyl group (Figure 2.10). In this sense the thiazolium anion is very much like cyanide anion, the normal catalyst for simple benzoin condensations. Benzaldehyde would be expected to bind into a j8-cyclodextrin cavity, so we attached a thiazolium salt to a primary carbon of j8-cyclodextrin and examined it as a catalyst. We found that this was not a better catalyst for the benzoin condensation, apparently because there was no room in the j8-cyclodextrin cavity for the binding of two benzaldehyde molecules. However it was clear that at least the reaction intermediate was being formed we got very rapid tritium exchange from the aldehyde by formation of the thiazolium adduct, and as well a very rapid oxidation of para-f-butyl benzaldehyde by ferricyanide ion since it was able to oxidize the reaction intermediate formed when the bound t-butyl benzaldehyde underwent addition of the thiazolium ring. 

Figure 2.10 Thiazolium salts catalyse the benzoin condensation, and with an extra rate when they are linked to y-cyclodextrin, which can bind two benzaldehydes into its large cavity...

R. Breslow, E. Kool, A y-cyclodextrin thiazolium salt holoenzyme mimic for the benzoin condensation. Tetrahedron Lett., 1988, 29, 1635-1638. 

On the basis of extensive work, Breslow found that the benzoin condensation in aqueous media using inorganic salts (e.g., LiCl) is about 200 times faster than in ethanol (without any salt). The addition of y-cyclodextrin also accelerates the reaction, whereas the addition of p-cyclodextrin inhibits the condensation. 

The conclusion that the two phenyl groups pack together in the benzoin condensation transition state was confirmed by the finding that this reaction is accelerated by y-cyclodextrin [14]. The cavity of this molecule is large... 

R. Breslow and E. Kool, "A y-Cyclodextrin Thiazolium Salt Holoenzyme Mimic for the Benzoin Condensation", Tetrahedron Lett.. 29,1635 (1988). 

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