Catalysis asymmetric ion-pairing

The topic of asymmetric ion-pairing catalysis has been extensively reviewed (142 references), over a wide range of reaction types. While the directional effect of electrostatic attraction is not particularly sffong, secondary non-covalent interactions can be exploited to build high stereoinduction. 

Brak K, Jacobsen EN (2013) Asymmetric ion-pairing catalysis. Angew Chem Int Ed 52 534... 

BINOL-phosphates as efficient Brpnsted acid catalysts in the enantios-elective Strecker reaction shows that C-nucleophiles can be applied in the chiral ion-pair catalysis procedure. This, in turn, not only increases the diversity of possible transformations of this catalyst but also shows the great potential chiral Brpnsted acids in asymmetric catalysis. 

In the Michael-addition, a nucleophile Nu is added to the / -position of an a,fi-unsaturated acceptor A (Scheme 4.1) [1], The active nucleophile Nu is usually generated by deprotonation of the precursor NuH. Addition of Nu to a prochiral acceptor A generates a center of chirality at the / -carbon atom of the acceptor A. Furthermore, the reaction of the intermediate enolate anion with the electrophile E+ may generate a second center of chirality at the a-carbon atom of the acceptor. This mechanistic scheme implies that enantioface-differentiation in the addition to the yfi-carbon atom of the acceptor can be achieved in two ways (i) deprotonation of NuH with a chiral base results in the chiral ion pair I which can be expected to add to the acceptor asymmetrically and (ii) phase-transfer catalysis (PTC) in which deprotonation of NuH is achieved in one phase with an achiral base and the anion... 

Most chemical reactions proceed via charged intermediates or transition states. In asymmetric Brpnsted acid catalysis the substrate is protonated by the catalyst and a chiral H-bond-assisted ion pair is generated. We reasoned that, in principle, any reaction that proceeds via cationic in-... 

Keywords Asymmetric catalysis Ion-pairing Organocatalysis Vinylogy... 

Asymmetric phase-transfer catalysis is a method that has for almost three decades proven its high utility. Although its typical application is for (non-natural) amino acid synthesis, over the years other types of applications have been reported. The unique capability of quaternary ammonium salts to form chiral ion pairs with anionic intermediates gives access to stereoselective transformations that are otherwise very difficult to conduct using metal catalysts or other organocatalysts. Thus, this catalytic principle has created its own very powerful niche within the field of asymmetric catalysis. As can be seen in Table 5 below, the privileged catalyst structures are mostly Cinchona alkaloid-based, whereas the highly potent Maruoka-type catalysts have so far not been applied routinely to complex natural product total synthesis. 

The chiral catalyst (15) is derived from natural 5,5-hydroxyproline, and serves to deprotonate the thiophenol. A tight ion pair is formed with (14), rather reminiscent of that in asymmetric phase-transfer catalysis. In a non-polar solvent such as toluene, solvation is at a premium, so one would expect the hydroxy of the catalyst to hydrogen bond to the carbonyl of the enone (17). 

In the same year, Xu et al developed an efficient example of asymmetric cooperative catalysis applied to a domino oxa-Michael-Mannich reaction of salicylaldehydes with cyclohexenones. The proeess was eatalysed by a combination of two chiral catalysts, such as a chiral pyrrolidine and amino acid D-tert-leucine. The authors assumed that there was protonation of the aromatic nitrogen atom of the pyrrolidine catalyst by u-te/t-leucine, which spontaneously led to the corresponding ion-pair assembly (Scheme 2.6). This self-assembled catalyst possessed dual activation centres, enabling the catalysis of the electrophilic and nucleophilic substrates simultaneously. The domino oxa-Michael-Mannich reaction provided a range of versatile chiral tetrahydroxanthenones in high yields and high to excellent enantioselectivities of up to 98% ee, as shown in Scheme 2.6. 

Chiral anion phase-transfer catalysis has been extended to the asymmetric synthesis of allylic fluorides (Scheme 7.10) [20]. The key with this chemistry was judicious selection of the electrophilic fluorine source. Selectfluor displays poor solubility in nonpolar solvents such as cyclohexane however, combining this F source with a chiral phosphate salt generated afforded a soluble ion pair that promoted the chemistry. A wide range of... 

Brpnsted) base functionality as the sole catalytically active group as well as those having an alternative H-bond donor like a hydroxy group (e.g., cinchona alkaloids) have found widespread applications in asymmetric catalysis [88]. The potential of these catalysts is due to the fact that a variety of different activation modes are possible, thus facilitating their application for different types of reactions. On the one hand, chiral (Brpnsted) bases can be used to carry out face-selective deprotonations and the formarion of chiral ion pairs, but, on the other hand, chiral (Lewis) bases can also be used as nucle-ophiUc catalysts, which represent a very important application field of chiral base catalysts. 

---