Covalent organocatalysis activation

The formation of covalent substrate-catalyst adducts might occur, e.g., by single-step Lewis-acid-Lewis-base interaction or by multi-step reactions such as the formation of enamines from aldehydes and secondary amines. The catalysis of aldol reactions by formation of the donor enamine is a striking example of common mechanisms in enzymatic catalysis and organocatalysis - in class-I aldolases lysine provides the catalytically active amine group whereas typical organocatalysts for this purpose are secondary amines, the most simple being proline (Scheme 2.2). 

There are a growing number of asymmetric organocatalytic reactions, which are accelerated by weak interactions. This type of catalysis includes neutral host-guest complexation, or acid-base associations between catalyst and substrate. The former case is highly reminiscent of the way that many enzymes effect reactions, by bringing together reactants at an active site and without the formation of covalent bonds. The chemistry of this organocatalysis is discussed in Chapter 13. 

Another important class of covalent catalysis is carried ont by chiral iV-heterocyclic carbenes [15] that react with carbonyl componnds forming chiral acyl anion eqniva-lents whose reaction with the corresponding electrophile complete the catalytic cycle (F, Fig. 2.2). Finally, it is worthy to mention the ability of certain bifnnctional organo-catalysts to perform simultaneous activation of the nncleophile and the electrophile. The nse of bifunctional organocatalysis has been shown to be very snccessfnl in conjngate additions. 

Asymmetric organocatalysis is remarkable both for the variety of its modes of activation and for the structural simplicity of most organocatalysts, a feature that has been cmcial for the generation of mechanistic working models that are able to rationalize, and in some cases even predict, the stereochemical outcome of organo-catalyzed reactions. From a mechanistic perspective, organocatalytic modes of activation can be classified according to (a) the covalent or noncovalent character... 

Organocatalysis has become an attractive and supplementary tool for mediating highly enantioselective cyclopropanations. By activating one or both substrates (electrophile and/or nucleophile) engaged in the reaction, either covalent activation (with... 

Since their renaissance in 2000, amine catalysts dominate the field of current organocatalysis, due to the robust covalent activation of various carbonyl compounds with excellent stereochanical control. With the development of organocatalysis, the advantages and limitations of certain chiral amines were investigated in detail. The... 

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