Chiral catalysts quinidine

The reaction of the aldehyde 219 with ketene, generated from acetyl chloride and i-Pr2NEt in the presence of a chiral quinidine catalyst, affords the /3-lactone 220 in 85 % yield (94 % e,e). ... 

Addition of p-tert-butylthiophenol 178 to the racemic furanone 168 in dry toluene, and in the presence of quinidine as a chiral catalyst, provided (/ )-168 together with the Michael adduct 179. The enantiomeric excess of the recovered furanone (R)-168 was determined via the addition of (/)-Q -methylbenzylamine This amine addition showed complete diastereofacial control to give the adduct 180 in quantitative yield (Scheme 50) (94T4775). 

Quinine and quinidine, as well as cinchonidine and cinchonine, are diastereo-meric pairs. However, at the critical sites—the P-hydroxyamine portions of the molecules—they are enantiomeric. Thus if quinine is used as the chiral catalyst in an asymmetric transformation (i.e., with one enantiomer being formed in excess), the other enantiomer is formed in excess when quinidine is used. Table 2 gives a representative example, the thiol addition reaction (19). 

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 cycloaddition of aldehydes and ketones with ketene under the influence of quinine or quinidine produce chiral 2-oxetanones [46,47]. Solvolytic cleavage of the oxetanone, derived from chloral, and further solvolysis of the trichloromethyl group leads to (5)- and (R)-malic acids with a 98% ee [46] (the chirality of the product depends on the configuration of the catalyst at C-8 and, unlike other alkaloid-induced reactions, it is apparently independent of the presence of the hydroxyl group). No attempts have been made to catalyse the reaction with chiral ammonium salts. 

Ricci et al. [85] reported the use of a quinidine-derived chiral catalyst in the asymmetric addition of nitromethane to iV-Boc imine 40. At around the same time, S chans and co-workers used a dihydroquinidine-derive chiral thiourea DHQD-134 applicable to nitromethane and nitroethane 149 [86]. The application of nitroethane conveniently generates a tertiary stereogenic center in the P-nitroamine product 151. The methodology presented by Schaus is also applicable to novel... 

Aldehydes, ketones, and quinones react with ketenes to give p-lactones, diphenylketene being used most often. The reaction is catalyzed by Lewis acids, and without them most ketenes do not give adducts because the adducts decompose at the high temperatures necessary when no catalyst is used. When ketene was added to chloral Cl3CCHO in the presence of the chiral catalyst (+ )-quinidine, one enantiomer of the p-lactone was produced in 98% enantiomeric excess.777 Other di- and trihalo aldehydes and ketones also give the reaction enantioselectively, with somewhat lower ee values.778 Ketene adds to another molecule of itself ... 

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 kinetic resolution of racemic alcohols is probably the most intensively studied aspect of organocatalysis, and its beginnings can be traced back to the 1930s [2, 3]. In these early attempts naturally occurring alkaloids such as (—)-brucine and (+)-quinidine were used as catalysts. Synthetic chiral tertiary amines also were introduced and examined, and enantiomeric excesses up to ca. 45% were achieved up to the early 1990s [4, 5]. 

It is interesting to note that the use of poly(quinine or quinidine) copolymers with acrylonitrile as a chiral catalyst in the reaction of )S-nitrostyrene with phenylmethanethiol results in an increase in the optical rotation of the sulfide products by a factor 3 to 67. 

Chiral Catalysis. Brucine has been utilized as chiral catalyst in a variety of reactions. For example, its incorporation into a polymer support provides a chiral catalyst for performing enan-tioselective benzoin condensations. It has also been used as a chiral catalyst in the asymmetric synthesis of (I )-malic acid via the corresponding p-lactone, which results from the asymmetric cycloaddition of chloral and ketene (eq 12). Though brucine yields malic acid with 68% ee, quinidine was found to be a more selective catalyst (98% ee). 

Platinum catalysts modified with members of the cinchona alkaloids are effective enantioselective catEilysts for the hydrogenation of a keto esters giving the chiral a hydroxy esters with ee s as high as 95%. >72 of the cinchona alkaloids, cinchonidine (30) and cinchonine (31) appear to be more effective than quinine (32) and quinidine (33). With cinchonidine the (R) lactate, 34, is... 

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... 

Later, the scope of this methodology was successfully extended to the intramolecular version by List and coworkers [14]. By employing 9-amino-9-deoxyepiquinine 24 as a catalyst (20 mol%) and an acid cocatalyst (AcOH, 60 mol%), 5-substituted-3-methyl-2-cydohexene-l-ones (26) were obtained with high enantioselectivity (up to 94% ee) from the diketones 25 via the intramolecular aldol reaction (Scheme 8.8). The chiral enones 26 are valuable synthetic building blocks for the synthesis of many biologically important compounds (e.g., HIV-1 protease-inhibitive didemnaketals). The pseudoenantiomeric quinidine analogue 23 of 24 also provided the opposite... 

It is interesting to recall that the first catalytic asymmetric reaction was performed on a racemic mixture (kinetic resolution) in an enzymatic reaction carried out by Pasteur in 1858. The organism Penicillium glauca destroyed (d)-am-monium tartrate more rapidly from a solution of a racemic ammonium tartrate [ 1 ]. The first use of a chiral non-enzymatic catalyst can be traced to the work of Bredig and Faj ans in 1908 [2 ]. They studied the decarboxylation of camphorcar-boxylic acid catalyzed by nicotine or quinidine, and they estabhshed the basic kinetic equations of kinetic resolution. 

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