Cinchonidine catalytic reaction

We have resolved racemic 5-methyl-2-cyclohexen-l-one by reaction in the presence of catalytic amounts of cinchonidine using a 1.5 L0 molar ratio of enone to thiophenol (excess enone) in benzene (55). The reaction (eq. [11]) was carried out at room temperature for 18 hr. The purified unreacted cyclohexenone had a rotation [a]2,578 of +47° (c = 1.0, CC14), indicating an optical purity of 59% and the S configuration. Thus the R isomer reacts faster with the thiophenol under these conditions. Sharpless (57) points out that even small differences in relative rate (e.g., 5-10) can provide useful amounts of a substance with high... 

Theoretical calculations proved that the reaction intermediate leading to R-ethyl lactate on cinchonidine-modified Pt(lll) is energetically more stable than the intermediate leading to the S-ethyl lactate [147], However, the catalytic system is complex and the formation and breaking of intermediates are transient, so it is certainly difficult to obtain direct information spectroscopically. It is therefore advisable to use simplified model systems and investigate each possible pairwise interaction among reactants, products, catalyst, chiral modifier, and solvent separately [147, 148]. In order to constitute these model systems, it is important to get initial inputs from specific catalytic phenomena. 

The use of compounds with activated methylene protons (doubly activated) enables the use of a mild base during the Neber reaction to 277-azirines. Using ketoxime 4-toluenesulfonates of 3-oxocarboxylic esters 539 as starting materials and a catalytic quantity of chiral tertiary base for the reaction, moderate to high enantioselectivity (44-82% ee) was achieved (equation 240). This asymmetric conversion was observed for the three pairs of Cinchona alkaloids (Cinchonine/Cinchonidine, Quinine/Quinidine and Dihydro-quinine/Dihydroquinidine). When the pseudoenantiomers of the alkaloid bases were used, opposite enantioselectivity was observed in the reaction. This fact shows that the absolute configuration of the predominant azirine can be controlled by base selection. 

Recently, Corey and coworkers prepared the cinchonidine-derived bifluoride 20 from the corresponding bromide by passage of a methanolic solution through a column of Amberlyst A-26 OH- form, and subsequent neutralization with 2 equiv. of 1 N HF solution and evaporation (the modified method C in Scheme 9.5). The catalytic activity and chiral efficiency of 20 (dried over P205 under vacuum) have been demonstrated by the development of a Mukaiyama-type aldol reaction of ketene silyl acetal 21 with aldehydes under mild conditions, giving mostly syw-P-hydroxy-a-amino esters 22 as the major diastereomer with good to excellent enantiomeric excesses (Table 9.4) [23],... 

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. 

Dehmlow and coworkers screened several analogues of dnchona-based PTCs bearing an N-(9-anthracenylmethyl) group [17]. Especially, in the case of 2-isopropyl naphthoquinones, the nonnatural deazacinchonidine derivative catalyst 11 showed better results compared to those obtained with the natural cinchonidine-derived analogue 12, in terms of both the catalytic activity and the enantioselectivity (84% ee) in this reaction (Scheme 5.12). 

The soluble polymer-supported catalysts 11 and 12 (Scheme 8.5) were prepared by attaching two different MeO-PEGsooo/spacer fragments to the N-anthracenyl-methyl salts of nor-quinine and cinchonidine, respectively [19], The behavior of the obtained catalysts, however, fell short of expectations. Whilst with 11 enantioselectivities lower than 12% ee were always obtained, 12 showed good catalytic activity in promoting the benzylation reaction (solid CsOH, DCM, -78 to 23 "C,... 

Enantiomeric excess and catalytic activity of the asymmetric hydrogenation of ethyl pyruvate over (-)cinchonidine modified Pt/carrier catalysts depend significantly on the specific Pt surface area This is due to the morphology of the Pt particles and to surface chemical Pt/support interaction. Thus, reaction pathway control is possible by varying these parameters. 

Early studies on the catalytic asymmetric Michael reactions were conducted with readily available amines of natural origin as hsted in Fig. 4. (-)-Quinine (1) and (+)-quinidine (2) are pseudo-enantiomeric concerning the aza[2.2.2]bicyclooc-tane and quinohne moiety, and generally give the antipodes. The same situation holds for (-i-)-cinchonine (3) and (-)-cinchonidine (4) which are demethoxylat-ed derivatives of 1 and 2. 

Another example worth mentioning is catalytic enantioselective hydrogenation of ketones. This reaction over non-chiral catalysts when a ketone contains a prochiral center produces racemic mixtures of optical isomers. The kinetics of 1 -phenyl-1,2-propanedione hydrogenation was studied in the presence of a chiral modifier -natural alkaloid cinchonidine (Figure 7.7)... 

Pt/a-alumina was active in the unmodified state for racemic hydrogenation of methyl pyruvate and in the cinchonidine-modified state for enantioselective hydrogenation of the ester. Conversions observed in reactions over unmodified and modified catalysts over the first hour of time on line are shown in Figure 1. Activity decayed with time in each case and modification by alkaloid reduced catalytic activity. 

Quintard and Alexakis examined the catalysis of the addition of cydic ketones to (Z)-l,2-bis(sulfone)vinylene 78 with their aminal secondary amine catalysts and obtained moderate enantioselectivities (64—73% ee) [75] while Lu s group used the more reactive and less sterically sensitive primary amines. The latter group [76] had shown that the primary amine derived from cinchonidine (94) was very efficient in this reaction with six-membered cyclic ketones 95 or prochiral ketones 96 (Scheme 34.34). Unprecedented enantioselectivity was obtained with this catalytic system on combining catalyst 94 and benzoic acid as additive under mild conditions while in the case of prochiral ketones 95 moderate diastereoselectivity was observed. 

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