Cinchona alkaloids features

The main features of the cinchona alkaloid-modified metal system are illustrated in Scheme 14.9. 

Enantioselective hydrogenation of a-ketoesters on cinchona alkaloid-modified Pt/Al203 is an interesting system in heterogeneous catalysis [143-146], The key feature is that on cinchonidine-modified platinum, ethyl pyruvate is selectively hydrogenated to R-ethyl lactate, whereas on einchonine-modified platinum, S-ethyl pyruvate is the dominant product (Figure 16) [143]. 

Figure 16. Main features in enantioselective hydrogenation of a-ketoesters on cinchona alkaloid-modified metal catalysts [ 143]. [Reproduced with permission of Elsevier from Baiker, A. J. Mol. Catal. A 1997,115, 473-493.]...

Esters 16b,c are used in reactions catalyzed by cinchona alkaloid-based phase-transfer catalysts, since the size of the ester is important for efficient asymmetric induction in these reactions [35], However, the syntheses of esters 16b,c adds considerable cost to any attempt to exploit this chemistry on a commercial basis. Fortunately, it was possible to develop reaction conditions which allowed the readily available and inexpensive substrate 16a to be alkylated with high enantios-electivity using catalyst 33 and sodium hydroxide, as shown in Scheme 8.18 [36]. The key feature of this modified process is the introduction of a re-esterification step following alkylation of the enolate of compound 16a. It appears that under... 

Catalytic asymmetric alkylations of 28 have also been carried out with polymer-bound glycine substrates [43], or in the presence of polymer-supported cinchona alkaloid-derived ammonium salts as immobilized chiral phase-transfer catalysts [44], both of which feature their practical advantages especially for large-scale synthesis. 

As mentioned in the previous section, nowadays, readily available and inexpensive cinchona alkaloids with pseudoenantiomeric forms, such as quinine and quinidine or cinchonine and cinchonidine, are among the most privileged chirality inducers in the area of asymmetric catalysis. The key feature responsible for their successful utility in catalysis is that they possess diverse chiral skeletons and are easily tunable for diverse types of reactions (Figure 1.2). The presence of the 1,2-aminoalcohol subunit containing the highly basic and bulky quinuclidine, which complements the proximal Lewis acidic hydroxyl function, is primarily responsible for their catalytic activity. 

Cinchona alkaloids have characteristic structural features for their diverse conformations and self-association phenomena. Therefore, knowledge of their real structure in solution can provide original information on the chiral inducing and discriminating ability of these alkaloids. 

Another characteristic structural feature of cinchona alkaloids is their multifunctional character and, thus, autoassociation phenomena are possible that could result in the strong dependency of their efficiency on the concentration and temperature [22, 23]. 

Figure 13.2 Structural features of cinchona alkaloid molecules (QN, quinine QD, quinidine CN, cinchonine CD, cinchonidine CPN, cupreine CPD, cupreidine).

One of the most appealing features with the Cinchona alkaloids as chiral ligands, is the pseudoenantiomeric relationship between dihydroquinine (DHQ)... 

Fig. 6. Summary of different features in cinchona alkaloid ligands and their effect on osmium tetroxide binding and ligand acceleration...

Wynberg studied the catalysis by Cinchona alkaloids [7,8]. Use of 1 in the addition of 6 to 3-buten-2-one (7) gave the optically active adduct (S)-8 in 76% ee (Scheme 1). As shown below, this prochiral donor reaction has become a standard to evaluate the efficiency of various catalysts. Several features of the reaction deserve comment ... 

The reactions of the cinchona toxines are in general those to be expected of substances contmning the structural features known to be present. The ready formation of a-isonitroso derivatives (XXI), and the cleavage of the latter to cinchoninic acid derivatives and meroquinene or its congeners has been mentioned in Section I. The interesting reactions which permit reconstitution of the cinchona alkaloid structure from the toxines are discussed in Section IV. 

In this context, there is a relevant example of a newly designed cinchona-alkaloid derived bis-ammonium salt 105 employed as catalyst in the Michael reaction of cyclic p-ketoesters with methyl vinyl ketone (Scheme 5.12). Excellent yields and moderate enantioselectivities of the corresponding Michael adducts were obtained under the best reaction conditions, which also allowed the use of an organic base (Hiinig base) for the deprotonation of the p-ketoester. However, perhaps the most relevant feature associated to the use of this catalyst is the fact that it can be easily separated from the reaction medium by precipitation in ether, which allowed its recycling for further uses without loss of activity. 

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