Chiral counterion catalysis

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). 

Hamilton GL, Kang EJ, Mba M, Toste FD (2007) A Powerful Chiral Counterion Strategy for Asymmetric Transition Metal Catalysis. Science 317 496... 

A powerful chiral counterion strategy for asymmetric transition metal catalysis, G. L. Hamilton, E. J. Kang, M. Mba, and F. D. Toste, Science, 2007, 317,496. 

Most of the work on chiral recognition in the ground state deals with salts having chiral, primary alkylammonium cations. Another approach is the chiral discrimination between two enantiomeric anions present as counterions in metal-cation complexes (Lehn et al., 1978). Discrimination between enantiomeric transition states will be dealt with in the next section together with non-chiral mimicry of enzymic catalysis. 

Cooperative catalysis by combing chiral phosphoric acids and Lewis acids to promote the FCA reactions between arenes and chelating enones were recently developed [29]. It was observed by Luo and co-workers that simple swap of the counterions of Lewis acid 10X3 led to a regioselective shift between 1,2-addition and 1,4-addition in the reactions of indoles with (S,7-unsaturated a-ketoesters (Scheme 9.11). 

Significant counterion effects are observed in the enantioselectivity of addition of diethylzinc to benzaldehyde using a titanium/a-acetyl-(5 )-BINOL system. rran5-l,2-Diaminocyclohexane - a common motif used in asymmetric catalysis - exhibits a dihedral angle of ca 60° between the amino groups, whereas rranx-ll,12-diamino-9,10-dihydro-9,10-ethanoanthracene (124) is constrained to >110°. Further functionality and chirality has been incorporated by the formation of bis-sulfonamides of (124), using (S j-camphor sulfonyl chloride. The... 

In the case of enals, the most common catalysts are secondary chiral amines, which can be divided into two large groups (i) amines substituted with a bulky group and (ii) amines with hydrogen-bond-directing groups. Another possible type of catalyst for this activation mode arises from ACDC (asymmetric counterion direct catalysis) developed by List. In these catalysts either a chiral or non-chiral amine forms a chiral ionic pair with a chiral phosphoric acid. A different possibility is the use of a primary chiral amine and a strong acid. These latter methods have... 

Asymmetric counterion direct catalysis (ACDC) was first reported by List in 2006 [14]. List was intrigued by the observation of a strong counterion effect on the yield and enantioselectivity in iminium catalyzed reactions, hypothesizing that catalytic salts of achiral amines (primary or secondary) and chiral phosphoric acids could induce asymmetry in the process. Later on, this powerful methodology was extended to other chiral acids or even to the combination of chiral amines and chiral acids. Rationalization of the stereochemical course of the reaction is almost impossible due the nature of the ion pair (Figure 33.7). 

However, these two procedures have an important limitation, the low enantioselectivities obtained when p,p-dialiphatic enals were used. To overcome this hmitation, list and coworkers applied the AC DC (asymmetric counterion direct catalysis) concept to this reaction [14]. When an achiral amine and a chiral phosphoric add were used together as a catalytic system for this reaction, p,P-dialiphatic enals were reduced with good yields and exceptional levels of enantioconhol. 

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]. 

Wanner et al. developed an efficient Pictet-Spengler reaction of secondary amines and aldehydes via the formation of active sulfenyliminium ions in situ from N-sulphenyltryptamine 16, catalyzed by chiral Brpnsted acids 5d (Scheme 2.6b) [9a], The enantioselectivity may be delivered from asymmetric counterion-directed catalysis [9a], Based on a similar strategy, they achieved the total synthesis of (+)-yohimbine via a phosphoric acid-catalyzed Pictet-Spengler reaction, which employed an A -(5-oxy-2,4-pentadienyl)tryptamine derivative and methyl 5-oxo-2(phenylseleno)pentanoate as starting materials [9b],... 

Hayashi and coworkers have developed the highly efficient enantioselective intramolecular [5+2] cycloaddition of heteroatom (O and NTs) alkyne-VCPs 31 under rhodium catalysis [29]. High enantioselectivities of up to >99% ee were achieved for the corresponding cycloadducts 32 by the use of the chiral phosphoramidite ligand 33 in combination with a catalyst such as [RhCKCaH lJi- The reactions were performed at 30 °C in dichloromethane as the solvent and in the presence of sodium tetrakis(3,5-bis(tiilluoromethyl)phe-nyl)borate (Barp) as source of anionic counterion, which produced a series of chiral heteroatom (O and NTs)-tethered cycloadducts in high yields, as shown in Scheme 20.13. 

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