Asymmetric counteranion-directed catalysis activation

Besides the utilization of chiral secondary amines to achieve a LUMO-lowering activation as well as face discrimination, the use of achiral secondary amines in combination with a chiral counterion also proved to be highly promising for such transformations. This strategy resembles the use of achiral metal catalysts in combination with a chiral ligand to achieve a stereoselective transformation (206-208). It is due to Benjamin List that the elegant concept of asymmetric counteranion-directed catalysis (ACDC) has found widespread applications in organocatalysis at the present time (209-212). 

While asymmetric counteranion-directed catalysis (ACDC) has been estab-hshed as a powerful strategy in iminium catalysis, enamine-based asymmetric counteranion-directed catalysis has not yet been developed. Recently, Lu et al. [32] demonstrated that the combination of a cinchona alkaloid-derived primary amine and chiral camphorsuhnnic acid (CSA) results in an effective ion-pair catalyst for the directed asymmetric amination of a-branched aldehydes through enamine activation (Scheme 43.21). 

Amino catalysts are one of the most dominant organocatalysts in the activation and transformation of aldehydes or ketones through enamine or iminium intermediates. Initially, the presence of an acid co-catalyst is crucial for the catalytic activation. Later it was reaUzed that the introduction of a chiral counteranion to the catalytic system enables the reactions proceeding through cationic intermediates to be conducted in a highly enantioselective manner, and thus stereochemical control could be effectively induced by the chiral counteranion. This strategy has been defined as asymmetric counterion-directed catalysis (ACDC) [25]. 

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