Quinidine chiral base

We have studied this reaction in considerable detail (88) and have found that when one uses quinine (eq. [25]) or any one of the chiral bases, a variety of aldehydes react with ketene to form the corresponding p-lactones in excellent chemical and nearly quantitative enantiomeric yields. Equation [25] exemplifies the reaction. Note that mild basic hydrolysis of the lactone furnishes a trichlo-rohydroxy acid that was prepared earlier by McKenzie (89). If one uses quinidine as catalyst, the process furnishes the natural (S)-malic acid. Note that ketene first acylates the free hydroxyl group of quinine, so that the actual catalyst is the alkaloid ester. 

The asymmetric hydrogenation of C—O bonds have now been achieved in optical yields up to 95%, rivalling the performance of alkenes. Here also, rhodium complexes have been used almost exclusively, but some success has been obtained with cobalt catalysts. Using [Co(HDMG)2] in presence of optically active bases, benzil could be reduced to benzoin (equation 54) in an optical yield of 78%. Quinine or quinidine were the chiral bases employed. The best optical yields were obtained with quinine (60). It was found that when benzylamine was also present, the rate of hydrogenation was greatly enhanced without any decrease in the optical yield.276... 

The interaction of a (2-halogenoethyl)phosphinate (129) with less than one molar proportion of a chiral base [(—)-quinine, (+)-quinidine, (+)-l-phenyl-ethylamine, and (—)-A -methylephedrine, were each used] results in elimination to give (130) with concurrent enrichment of the less reactive phosphinate enantiomer (129). The leaving group evidently plays a significant role in the... 

An important addition was the work by Kagan involving chiral amines in cycloaddition reactions. Kagan showed that chiral bases such as quinidine or prolinol catalyze the cycloaddition between anthrones and maleimides with moderate enantioselectivities [21]. 

The first asymmetric chiral-base catalyzed Diels-Alder reaction of anthrone 79 with maleimide 80 was achieved by Kagan and Riant in 1989 [4]. With the use of quinidine (81) as catalyst, the cycloadduct 83a can be obtained in 97% yield with 61% ee (Scheme 38.23). The enantioselectivity was further improved to 87% by... 

Interestingly, certain chiral tertiary bases, viz., the Cinchona alkaloids, result in an asymmetric 1,3-elimination to give enantiomerically enriched azirine esters 29 (Scheme 15). The best results were obtained with quinidine in toluene as the solvent at a rather high dilution (2 mg mL ) at 0 °C. In an alcoholic solvent no asymmetric conversion was observed. It is of importance to note that the pseudoenantiomers of the alkaloid bases gave opposite antipodes of the azirine ester, whereby quinidine leads to the predominant formation of the (k)-enan-tiomer (ee = -80%). To explain this asymmetric Neber reaction, it is suggested... 

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. 

All catalytic enantioselective versions of the Darzens condensation are based on the use of chiral phase-transfer agents, e.g. the cations 184a,b derived from ephed-rine, quinine/quinidine-based ammonium ions such as 185a,b, or the crown ether 186. 

More successful asymmetric reductions have been based on amine (particularly alkaloid) complexes of bis(dimethylglyoximato) cobalt(II), also known as cobaloxime(II) and represented Co(dmg)2 (compound VII). Cobaloxime-chiral amine complexes have been used to catalyze the hydrogenation of both olefinic and ketonic substrates (Fig. 24). It has been determined that hydroxyamine modifiers, for example, alkaloids such as quinine, quinidine, and cinchonidine, are most effective. The highest optical purity obtained thus far has been 71%, observed for reduction of benzil in benzene solution at 10° using quinine as the... 

M. Lammerhofer and W. Lindner, Quinince and quinidine derivatives as chiral selectors. Beush type chiral stationary phases for high performance liquid chromatography based on chincona carbamates and their applications as chiral anion exchanger, J. Chromatogr. 741 (1966), 33. 

The cinchona alkaloid-based stationary phases are chiral stationary phases where quinine/ quinidine are chemically bonded to a silica gel matrix. The interaction between the selectand and selector is based on charge transfer n-n interactions as well as ion pairing with the selector. They operate under aqueous-organic mobile phases or mixtures of organic solvents such as hexane-alcohols. 

Very recently, using structurally varied PTCs based on quinine, quinidine, dihydroquinine, and dihydroquinidine, Berkessel and coworkers conducted the asymmetric epoxidation of 2-methylnaphthoquinone (precursor of vitamin K3) with an aqueous solution of NaOCl at —10 °C in chlorobenzene [18], Among these new catalysts, the phase-transfer catalyst 13 bearing an extra chiral moiety at the quinudidine nitrogen atom provided an enantioseledivity of 79% ee with good yield (86%). However, it was found that the best results were achieved with the readily... 

Recently, Lindner and coworkers developed a series of anion-exchange CSPs based on quinine and quinidine as chiral selectors (Fig. 6.11) [79, 80]. These phases are particularly appropriate for the separation of the enantiomers of chiral acidic compounds. Improvement of the chiral recognition power of these phases by rationally designed structural modifications has led to exceptionally high enantioselectivity which, of course, is of great interest for preparative applications [81]. Screen-... 

Fig. 7.22 (A) Chemical structures of the quinine and quinidine tert-butylcarbamate-based CHIRALPAK QN-AX and CHIRALPAK QD-AX anion exchange-type CSPs. These CSPs show pseudo-enantiomeric chiral recognition pro-...

Quinidine [3, (9S)-6 -methoxy-9-cinchonanol] is mostly applied for the same purposes as quinine, such as the addition of zinc alkyls to carbonyl compounds (Section D 1.3.1.4.), or addition of thiophenol to acrylic derivatives (Section D.2.I.). An important technical synthesis of malic acid is based on the quinidine catalyzed enantioselective [2 + 2] cycloaddition of ketene to chloral (see Section D. 1.6.1.3.). Esters and ethers of dihydroquinidine (4) (just like the corresponding derivatives of dihydroquinine) have been used as chiral ligands in osmium tetroxide catalyzed dihydroxylations of alkenes (Section D.4.4.). 

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). 

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