Historical Evolution of Asymmetric Organocatalysis

The possibility that small organic molecules could catalyze organic transformations in a stereoselective way can even be considered as a key element in the origins of life, as it is widely accepted that the source of homochirality in biological systems should be attributed to the presence of enantiomerically enriched a-amino acids in meteorites, and especially once it was demonstrated that these a-amino acids were able to catalyze aldol reactions in a stereoselective way under prebiotic conditions conducing to sugar-type products.  

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction.  

Finally, other important contributions that should be cited as very relevant with regard to the evolution of the organocatalysis field are those related to the use of stable A-heterocyclic carbenes as catalysts. The basis of this chemistry also finds its roots at the very early beginnings of organic synthesis, in particular in the well-known cyanide-catalyzed benzoin condensation by Liebig and Wholer, and 

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