Cinchona alkaloids catalytic reactions

Aza-Henry reaction is rendered asymmetric by quaternary salts of Cinchona alkaloids. Addition reactions. Changing the 9-hydroxy group of Cinchona alkaloids to a 9-epiamino group not only is synthetically expedient, such products often show excellent catalytic activities in many asymmetric reactions. Those derived from dihydrocinchona alkaloids mediate Michael reactions to good results, including addition of indole to enones, and carbonyl compounds to nitroalkenes. Salt 4 has also been successfully employed in the alkenylation of t-butyl a-aryl-a-cyanoacetate. ... 

Azirines can be prepared in optically enriched form by the asymmetric Neber reaction mediated by Cinchona alkaloids. Thus, ketoxime tosylates 173, derived from 3-oxocarhoxylic esters, are converted to the azirine carboxylic esters 174 in the presence of a large excess of potassium carbonate and a catalytic amount of quinidine. The asymmetric bias is believed to be conferred on the substrate by strong hydrogen bonding via the catalyst hydroxyl group <96JA8491>. 

Another microwave-mediated intramolecular SN2 reaction forms one of the key steps in a recent catalytic asymmetric synthesis of the cinchona alkaloid quinine by Jacobsen and coworkers [209]. The strategy to construct the crucial quinudidine core of the natural product relies on an intramolecular SN2 reaction/epoxide ringopening (Scheme 6.103). After removal of the benzyl carbamate (Cbz) protecting group with diethylaluminum chloride/thioanisole, microwave heating of the acetonitrile solution at 200 °C for 2 min provided a 68% isolated yield of the natural product as the final transformation in a 16-step total synthesis. 

In order to evaluate the catalytic characteristics of colloidal platinum, a comparison of the efficiency of Pt nanoparticles in the quasi-homogeneous reaction shown in Equation 3.7, with that of supported colloids of the same charge and of a conventional heterogeneous platinum catalyst was performed. The quasi-homogeneous colloidal system surpassed the conventional catalyst in turnover frequency by a factor of 3 [157], Enantioselectivity of the reaction (Equation 3.7) in the presence of polyvinyl-pyrrolidone as stabilizer has been studied by Bradley et al. [158,159], who observed that the presence of HC1 in as-prepared cinchona alkaloids modified Pt sols had a marked effect on the rate and reproducibility [158], Removal of HC1 by dialysis improved the performance of the catalysts in both rate and reproducibility. These purified colloidal catalysts can serve as reliable... 

Alcoholysis of meso-cycYic anhydrides offers a versatile route to succinate and glu-tarate half-esters. Although a number of stoichiometric approaches to this problem have been investigated, a successful catalytic version of this reaction appeared as recently as 2003. ° Bolm and coworkers have developed a protocol for the metha-nolysis of a variety of succinic anhydrides using cinchona alkaloids [Eq. (10.50)]. The reaction may be made catalytic in alkaloid when pentamethylpiperidine is used as a stoichiometric additive. A moderate decrease in enantioselectivity is observed in a number of cases, although excellent selectivities are still attainable. More problematic is the reaction time (6 days under catalytic conditions) ... 

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. 

The Soos group, in 2005, prepared the first thiourea derivatives from the cinchona alkaloids quinine QN (8S, 9R-121), dihydroquinidine DHQD (8S, 9S-122), C9-epi-QN (8S, 9P-123), and quinidine QD (SR, 9R-124) via an experimentally simple one-step protocol with epimerization at the C9-position of the alkaloid starting material (Figure 6.39) [278]. The catalytic efficiency of these new thiourea derivatives and also of unmodified QN and C9-epi-QN was evaluated in the enan-tioselective Michael addition [149-152] of nitromethane to the simple model chal-cone 1,3-diphenyl-propenone resulting in adduct 1 in Scheme 6.119. After 99h reaction time at 25 °C in toluene and at 10 mol% catalyst loading QN turned out to be a poor catalyst (4% yield/42% ee (S)-adduct) and C9-epi-QN even failed to accelerate the screening reaction. In contrast, the C9-modified cinchona alkaloid... 

Recent developments in the understanding of the mechanisms of catalytic and asymmetric dihydroxylation reactions are discussed in Section V,E,l,b. An important aspect of this work is the kinetics and thermodynamics of the formation of adducts with N heterocycles, which have an important role in promoting many reactions. The crystal structure of the [0s04] adduct with the cinchona alkaloid ligand (dimethyl-... 

Cinchona alkaloids, naturally ubiquitous /3-hydroxy tertiary-amines, are characterized by a basic quinuclidine nitrogen surrounded by a highly asymmetric environment (12). Wynberg discovered that such alkaloids effect highly enantioselective hetero-[2 -I- 2] addition of ketene and chloral to produce /3-lactones, as shown in Scheme 4 (13). The reaction occurs catalytically in quantitative yield in toluene at — 50°C. Quinidine and quinine afford the antipodal products by leading, after hydrolysis, to (S)- and (/ )-malic acid, respectively. The presence of a /3-hydroxyl group in the catalyst amines is not crucial. The reaction appears to occur... 

S,y-Unsaturated a-keto esters such as tnms -MeCH=CHCOCC>2Et undergo enan-tioselective reaction with nitromethane, using new catalytic auxiliaries based on cinchona alkaloids.145 Carried out at -20 °C in DCM, the organocatalysts give high conversion, predominantly reaction at ketone only (typically <5% of product involves simultaneous addition to the alkene), and up to 97% ee. 

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],... 

Figure 3.39 a The structure and proposed mode of action of the modified Cinchona alkaloid catalyst b an example ofthe catalytic Henry reaction between benzaldehyde and nitromethane. 

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