Summary of Cinchona-Mediated Enantioselective Protonations

Overall, cinchona alkaloids, which are already powerful (organo)catalysts in most major chemical reactions, will be expected to be major players in the enantioselective protonations of enols/enolates. This will persuade the synthetic chemist to incorporate these methodologies with confidence in total syntheses. 

27 Except in one particular example where 99% ee was obtained, see Muzart, J., Henin, F., and Aboulhoda, S.J. (1997) Tetrahedron Asymmetry, 8, 381-389. 

The enantioselective nucleophilic addition of prochiral C=0 and C=N moieties to the corresponding saturated chiral products is one of the most important stereoselective transformations on both the laboratory and the industrial scale. Although, over the past few decades, remarkable scientific achievements have been made in these research areas by using a variety of transitional metal-based catalysts, the sensitivity of the reaction to moisture and oxygen, as well as the toxic metal contamination of the product, usually restrict its practical application. Thus, currently, there is much interest in chiral organocatalysts, as they tend to be less toxic and more environmental friendly than traditional metal-based catalysts [1]. They are usually robust and thus tolerate moisture and oxygen, so that they usually do not demand any special reaction conditions. 

In this chapter, the current state of the art on the applications of cinchona alkaloids and their derivatives as chiral catalysts in the enantioselective nucleophilic addition of prochiral C=0 and C=N bonds is discussed. The schemes exemplified in this chapter demonstrate the indispensable role of cinchona alkaloids as catalysts in these important research areas. 

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