Cinchona Alkaloids in Organic Catalysis

Key words

cinchona alkaloids - benzaldehyde - hydrogen cyanide

Significance

In 1912, Bredig and Fiske published the first example of asymmetric (nonenzymatic) (organo)catalysis. They reported the addition of HCN to benzaldehyde catalyzed by the pseudo­enantiomeric alkaloids quinine and quinidine, with low but reproducible enantioselectivities. About four decades later, Pracejus, for the first time, achieved reasonable enantioselectivities (74% ee) by using O-acetylquinine as an organocatalyst. This groundwork paved the way to a variety of cinchona-alkaloid-catalyzed asymmetric transformations in industry and academia.

Comment

Cinchona alkaloids are among the most privileged asymmetry inducers in the area of enantioselective catalysis. They possess a chiral skeleton that is easily modifiable. In the last century, methodologies were developed in which they were used as chiral bases, as chiral Lewis base catalysts, in ligand-accelerated catalysis, or as quaternized ammonium salts in phase-transfer catalysis, among others. Current research continues to showcase their importance and utility in asymmetric catalysis, for example by incorporating other privileged organic catalophores such as thioureas.