Asymmetric counteranion-directed catalysis catalysts

Scheme 24. Asymmetric counteranion-directed catalysis catalyst synthesis and screening...

A new catalyst salt (20) that consists of an achiral ammonium ion and a chiral phosphate anion and which catalyses highly enantioselective transfer hydrogenations of ,/J-unsaturated aldehydes to the corresponding saturated derivatives has been developed. The underlying principle, namely asymmetric counteranion-directed catalysis, is claimed to be a new strategy for highly enantioselective synthesis.357... 

Scheme 28. Asymmetric counteranion-directed catalysis transfer hydrogenation of different enones with catalyst 35...

S.C. PanandB. List s paper spans the whole field of current organocat-alysts discussing Lewis and Brpnsted basic and acidic catalysts. Starting from the development of proline-mediated enamine catalysis— the Hajos-Parrish-Eder-Sauer-Wiechert reaction is an intramolecular transformation involving enamine catalysis—into an intermolecular process with various electrophilic reaction partners as a means to access cY-functionalized aldehydes, they discuss a straightforward classification of organocatalysts and expands on Brpnsted acid-mediated transformations, and describe the development of asymmetric counteranion-directed catalysis (ACDC). 

In 2008, List s group developed an epoxidation using asymmetric counteranion-directed catalysis (ACDC) [177]. In this work, the epoxidation of 1,2-disubstituted enals (33) and (3,(3-disubstituted, a, 3-unsaturated aldehydes (115) was explored. Instead of using a chiral amine (e.g. Jprgensen-Hayashi s catalyst), an achiral amine and a chiral counteranion (a phosphoric acid derived from BINOL), were employed. 

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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