Structural Information on Cinchona Alkaloids

Cinchona alkaloids have characteristic structural features for their diverse conformations and self-association phenomena. Therefore, knowledge of their real structure in solution can provide original information on the chiral inducing and discriminating ability of these alkaloids. 

The pivotal role of the conformational behavior of a cinchona alkaloid (e.g., cinchonidine) in its enantioselectivity was nicely illustrated in the platinum-catalyzed enantioselective hydrogenation of ketopantolactone in different solvents [18]. The achieved enantiomeric excess shows the same solvent dependence as the fraction of anti-open conformer in solution, suggesting that this conformer plays a crucial role in the enantiodifferentiation. As a more dramatic example, the solvent affects the absolute chirality of the product in the 1,3-hydron transfer reaction catalyzed by dihydroquinidine [20]. An NMR study revealed that the changes in the ratio between the two conformers of dihydroquinidine can explain the observed reversal of the sense of the enantioselectivity for this reaction when the solvent is changed from o-dichlorobenzene (open/closed 60 40) to DMSO (open/dosed 20 80). 

Undoubtedly, the modification of the structure of the cinchona alkaloid also has a significant effect on its conformational behavior in solution esters [17] and 9-0-carbamoyl derivatives [21] exist as a mixture of two major anti-closed and anti-open conformers, while C9 methyl ethers prefer an anti-closed arrangement in noncoordinating solvents [17]. Here again, protonation provides the anti-open conformation as the sole stable form [16b]. In addition to the solvent polarity, many other factors such as intermolecular interactions are also responsible for the complex conformational behavior of cinchona alkaloids in solution. 

Another characteristic structural feature of cinchona alkaloids is their multifunctional character and, thus, autoassociation phenomena are possible that could result in the strong dependency of their efficiency on the concentration and temperature [22, 23]. 

Quite recently, we also observed that quinine-based thiourea derivatives showed dramatic concentration and temperature effects on the enantioselectivity in the alcoholytic desymmetrization ofmeso-cyclic anhydrides, which can also be attributed to the self-association of the catalyst [23]. Of course, the possibility that the variation in 

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