Asymmetric counteranion-directed catalysis

Mayer, S. and List, B. Asymmetric Counteranion-directed Catalysis. Angew. Chem. Int. Ed. 2006, 45, 4193 195. 

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... 

Asymmetric Bransted Acid Catalysis Asymmetric, Counteranion-Directed Catalysis Scheme 21. Asymmetric counteranion-directed catalysis... 

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

Scheme 25. Asymmetric counteranion-directed catalysis transfer hydrogenation of enals...

Martin NJ, List B (2006) Highly enantioselective transfer hydrogenation of alpha,beta-unsaturated ketones. J Am Chem Soc 128 13368-13369 Mayer S, List B (2006) Asymmetric counteranion-directed catalysis. Angew Chem Int Ed Engl 45 4193 1195... 

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). 

The transfer hydrogenation of ketones was subsequently attempted, although for these more challenging substrates chiral primary amines such as L-valine terf-butyl ester were required in order to obtain good yields (68-99%) and enantioselectivities (70-98% ee) [168]. The reaction most likely involves an iminium-phosphate hydrogen bond. Another important application of asymmetric counteranion-directed catalysis developed by the List group is the chiral phosphate anion-directed epoxidation of a, 3-unsamrated carbonyls [169]. 

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). 

Mayer S, List B (2006) Asymmetric Counteranion-Directed Catalysis. Angew Chem Int Ed 45 4193... 

The validity of this approach was further demonstrated by the poor enantiose-lectivities obtained for proline-based catalytic centers that are imable to self-assemble with alkaloids, demonstrating that enantioselectivity is indeed due to the two-component supramolecular complex. As stated by the authors, these results indicate that this catalytic system is different from the reported asymmetric counteranion-directed catalysis (ACDC) [21] since in that case the stereocontrol is achieved mainly through steric effects instead of hydrogen bonding. 

The discrimination of the face of the chiral carbenium ion is determined by the hindrance of the flanking groups. In the case of chiral Bronsted acids, the chiral counter ion, formed after effective protonation or partial donation of the proton, surrounds the created cationic intermediate. One face of the intermediate is effectively covered by the chiral counter ion and the nucleophile reacts with the less covered face. However, in many SNl-type transformations mediated by Lewis acids, a transition state in which a couple of protons interact with the phosphates is often invoked. This double interaction seems cmcial and only a partial success in the use of nucleophiles was achieved. Nevertheless, a series of successful S l-type reactions were discovered and are highUghted in this section. The chiral ion pairs between phosphate anions and iminiums [64] or metal ions were developed [65]. This powerful strategy is called asymmetric counteranion-directed catalysis (ACDC) and it has been applied successfully to several innovative transformations. The generation of carbenium ion in situ from alcohol, with the use of acids able to form a tight chiral ion pair with the phosphate anion, can be used in S il-type... 

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). 

Asymmetric Counteranion-Directed Catalysis (ACDC) Instead of forming a chiral iminium ion that induces stereoinduction, the ACDC concept is based on the stereochemical communication between an achiral imine and a chiral phosphate anion. To incorporate both moieties into one substance, an organic salt consisting of a chiral phosphate anion and an achiral ammonium counterpart is used. ... 

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