Phase cinchona-based

Epoxidation of Enones and a, 3-Unsaturated Sulfones Using Cinchona-Based Chiral Phase-Transfer Catalysts... 

In the presence of cinchona derivatives as catalysts, peroxides or hypochlorites as Michael donors react with electron-deficient olefins to give epoxides via conjugate addition-intramolecular cyclization sequence reactions. Two complementary methodologies have been developed for the asymmetric epoxidation of electron-poor olefins, in which either cinchona-based phase-transfer catalysts or 9-amino-9(deoxy)-epi-dnchona alkaloids are used as organocatalysts. Mechanistically, in these two... 

Asymmetric Cycloaddition Catalyzed by Cinchona-Based Phase-Transfer Catalysts 321... 

It has been suggested that cinchona bases, although most valuable chiral auxiliaries (e.g., the AD reaction [5] and asymmetric phase-transfer reactions [6]), are very unlikely to find application as (chiral) building blocks [7]. The recent developments outlined herein will change this view. 

A significant breakthrough in cinchona-based enantioselective chromatography came with the demonstration by Lindner et al. in 1996 that immobilized quinine or quinidine 9-O-carbamates under polar organic or reversed phase condition efficiently resolved a number of acidic racemates, with opposite elution orders compared to unmodified QN or QD CSPs [44, 61]. Cinchona 9-O-carbamates contain a new functionality that can serve as a binding site of double character, that is, an H-bond donor-acceptor and, depending on the N-substituent, it may also provide a steric barrier or possibly a source of %-% interaction (Figure 13.11). 

Cinchona-Based Chiral Modifiers and Phases in Capillary Electrophoresis and Capillary Electrochromatography... 

A special subclass of brush-type chiral stationary phases are the ion-exchange CSPs developed by Lammerhofer and Lindner (1996). By introducing an additional ionic moiety, a strong interaction between the selector and the selectand can be achieved. The first commercial available phases are based on the Cinchona alkaloids Quinine and Quinidine with an additional weak anion-exchange function offering good separation possibilities for chiral acids. A strong dependence of the capacity from the counter ion of the mobile phase could be demonstrated by Arnell (2009). 

Scheme 1.30 Michael additions of cyclic P-keto esters to electron-deficient allenes catalysed by cinchona-based phase-transfer catalyst.

Cinchona Alkaloid-Derived Quaternary Ammonium Salts The first successful application of cinchona-based quaternary ammonium salts as chiral phase-transfer catalysts was conducted by the Merck research group in 1984 [16]. Dolling and coworkers reported the N-p-trifluoromethylbenzylcinchoninium bromide 11a for the highly enantioselective alkylation of indanone derivatives imder phase-transfer conditions (Figure 12.3). 

Corey et al. [20] developed the catalyst 12c, which showed superior results to Lygo s catalysts in the same reaction at very low temperature. They provided a general idea in the cinchona-based phase-transfer catalyst design the quaternary... 

A phenolic OH group in the C6 position of the quinoline ring at the scaffold of the cinchona-based phase-transfer catalyst may also have a dramatic effect on its performance. In 2007, the Berkessel group concluded that catalyst 16 provided better enantioselectivity than any other catalysts without free hydroxy groups at the 6 -position in the epoxidation of vitamin Kj [49] (Figure 12.6). Computational studies showed that catalyst 16 had the ability to form an additional hydrogen bond between the 6 -OH group and the substrate. 

The first silica-supported CSP with a cinchona alkaloid-derived chromatographic ligand was described by Rosini et al. [20]. The native cinchona alkaloids quinine and quinidine were immobilized via a spacer at the vinyl group of the quinuclidine ring. A number of distinct cinchona alkaloid-based CSPs were subsequently developed by various groups, including derivatives with free C9-hydroxyl group [17,21-27] or esterified C9-hydroxyl [28,29]. All of these CSPs suffered from low enantiose-lectivities, narrow application spectra, and partly limited stability (e.g., acetylated phases). 

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