Alkaloids pseudo-enantiomeric

A similar approach was reported by Lygo and co-workers who applied comparable anthracenylmethyl-based ammonium salts of type 26 in combination with 50% aqueous potassium hydroxide as a basic system at room temperature [26, 27a], Under these conditions the required O-alkylation at the alkaloid catalyst s hydroxyl group occurs in situ. The enantioselective alkylation reactions proceeded with somewhat lower enantioselectivity (up to 91% ee) compared with the results obtained with the Corey catalyst 25. The overall yields of esters of type 27 (obtained after imine hydrolysis) were in the range 40 to 86% [26]. A selected example is shown in Scheme 3.7. Because the pseudo-enantiomeric catalyst pairs 25 and 26 led to opposite enantiomers with comparable enantioselectivity, this procedure enables convenient access to both enantiomers. Recently, the Lygo group reported an in situ-preparation of the alkaloid-based phase transfer catalyst [27b] as well as the application of a new, highly effective phase-transfer catalyst derived from a-methyl-naphthylamine, which was found by screening of a catalyst library [27c],... 

It was mentioned at the beginning of this chapter that alkaloids were among the first catalysts to be used for asymmetric hydrocyanation of aldehydes. More recent work by Tian and Deng has shown that the pseudo-enantiomeric alkaloid derivatives 5/6 and 7/8 catalyze the asymmetric addition of ethyl cyanoformate to aliphatic ketones (Scheme 6.6) [50]. It is believed that the catalytic cycle is initiated by the alkaloid tertiary amine reacting with ethyl cyanoformate to form a chiral cyanide/acylammonium ion pair, followed by addition of cyanide to the ketone and acylation of the resulting cyanoalkoxide. Potentially, the latter reaction step occurs with dynamic kinetic resolution of the cyano alkoxide intermediate... 

Phase-transfer catalysis has been widely been used for asymmetric epoxidation of enones [100]. This catalytic reaction was pioneered by Wynberg et al., who used mainly the chiral and pseudo-enantiomeric quaternary ammonium salts 66 and 67, derived from the cinchona alkaloids quinine and quinidine, respectively [101-105],... 

The cinchona alkaloids are particularly valuable ligands in asymmetric addition of diethylzinc to a N-diphenyl phosphinoylimine (228) leading to enantiomerically enriched (R)- and (S)-N-(l-phenylpropyl-diphenylphosphinic amide) (229). Cinchonine and cinchonidine were found to be the pseudo-enantiomeric pair which gave the adduct in highest enantiomeric excess (up to 93% ee) (Scheme 62)." ... 

Modifier The effect of the modifier structure is also quite similar to that found for a-ketoesters [7]. Cinchonidine derivatives and quinine lead to an excess of the (R)-hydroxy-acid while the pseudo-enantiomeric cinchona alkaloids (cinchonine and quinidine) give preferentially (S)-product but with much lower enantioselecdvity. Changing the substituent Y at C9 has only an effect on the degree of asymmetric induction but not its direction. OMe and OH are more effective than OAc or H. An interesting exception are the Nj alkylated Cd derivatives which are completely ineffective in the case of the ester. Here, N-methyl-Cd+Cr gives a small excess of the R-enantiomer while N-benzyl-Cd Cl leads an 33% excess of (S)-4-phenyl-2-hydroxybutyric acid ... 

The two alkaloid auxiliaries, DHQ and DHQD, have a pseudo-enantiomeric relationship, defined by opposite configurations at the two central carbon atoms, affording enantiomeric products with similar enantioselectivity (Scheme 14.10). 

S)-proline-catalyzed reaction is not sufficient therefore, a large number of (S)-proline-derived secondary amine catalysts have been developed. Primary amine catalysts derived from natural amino acids and cinchona alkaloids have also emerged as highly versatile and powerful catalysts [25]. For example, in the intramolecular 6-endo aldol reaction of diketone 43, quinine-derived primary amine 44 in acetic acid affords the cyclic ketone (S)-46 in 94% yield with 90% ee (Scheme 28.3) (S)-prohne gives the cycUzation product in low yield with moderate ee. In addition, the pseudo-enantiomeric quinidine-derived primary amine 45 deUvers the opposite product, the (R)-enantiomer 46, with similar yield and enantioselectivity [26]. 

These nitrogen-containing natural products, often with powerful biological properties, are not usually incorporated into target molecules. However, they are important in asymmetric syntheses as the foundations of many reagents and catalysts. Quinine 119 is familiar as an anti-malarial and an ingredient in tonic water. Quinine and its twin cinchona alkaloid quinidine 118 are referred to as pseudo enantiomers. Each occurs naturally as one enantiomer only but the two structures are nearly enantiomeric only the vinyl side-chains disturb the symmetry and they act as enantiomers. The vinyl side-chains are reduced and two molecules of, say, dihydroquinine (DHQ) are joined... 

---