Cinchona bases

Stereoisomerism in the Cinchona Bases It was at first common practice to number the four asymmetric carbon atoms indicated in the general formula (I), 1, 2, 3 and 4, but this is now replaced by the more general system introduced by Rabe, who suggested the name ruban for (HI), which can be regarded as the parent substance of the natural cinchona alkaloids, and rubatoxan (IV) for that of the quinicines (quinatoxines). The formifiae, with notation, for ruban (III) and rubatoxan (IV) are shown below, and the general formula (I) for cinchona bases has been numbered in accordance with that scheme. 

Quinine Equia alents of Cinchona Bases and Transformation Products. 

The central. CHOH. group in the cinchona alkaloids seems to be essential to anti-malarial activity Conversion into quinicines [quinatoxines (I) — (VII)] destroys activity and so do such changes as. CHOH. — . CHCl. (cinchona chlorides) or. CHOH. — . CHj. (deoxy-cinchona bases) or. CHOH. — . CO. quina-ketones), or acylation of the hydroxyl group except in the case of quinine ethylcarbonate. 

Of the other cinchona bases, the dextrorotatory forms cinchonine and quinidine have been used as anti-malarial drugs in cases of idiosyncrasy to quinine, a subject to which Dawson has given much attention. Quinidine is used to eontrol auricular fibrillation, and its value for this purpose in comparison with dihydroquinidine has been investigated by several workers. Dawes has recently devised a method of testing... 

Asymmetric catalytic osmylation.s Chiral cinchona bases are known to effect asymmetric dihydroxylation with 0s04 as a stoichiometric reagent (10, 291). Significant but opposite stereoselectivity is shown by esters of dihydroquinine (1) and of dihydroquinidine (2), even though these bases are diastereomers rather than enantiomers. 

Poor stereoselectivity (<30% ee) is recorded for the Michael addition of 1,3-di-ketones with nitroalkenes using cinchona bases [50] and early work recorded <25% ee using N-methylquininium and quinidinium hydroxides [51, 52], In contrast, indanones have been reported to react with methyl vinyl ketone in the presence of a cinchoninium salts to produce a chiral (S)-product in >95% yield (80% ee) [7]. Surprisingly, the (R)-isomer is obtained less readily (ee 40-60%) using cinchoni-dinium salts. Both isomers are obtained in high optical purity (>80% ee) via alkylation with 1,3-dichlorobut-2-ene and subsequent ring closure yields the Robinson... 

The mechanism by which cinchona-based catalyst systems effect such selective ring-opening of anhydrides and related systems has been the subject of extensive... 

J. Other indole alkaloids (including andranginine, adina bases, and cinchona bases)... 

Addition of the thiophenolate anion to the / -carbon atom of the enone is the chirality-determining step it is, at the same time, rate-determining. The transition state is a ternary complex comprising the catalytic base in the protonated form, the thiophenolate anion, and the enone. The last is activated to nucleophilic attack by hydrogen-bonding to the catalysts / -hydroxy group. The chiral cinchona bases thus act as bifunctional catalysts. 

Disubstituted flavanones and chromanones are produced with good enantioselectivity from chalcones activated by an a-fert-butyl ester function through an intramolecular Michael addition catalysed by a chiral thiourea derivative. In situ decarboxylation enhances the ee and yields remain high <07JA3830>. A comprehensive study of the asymmetric cyclisation of 2 -hydroxychalcones to flavanones has refuted the ability of camphorsulfonic acid to achieve enantioselectivity but has shown that cinchona-based catalysts can be effective <07EJO5886>. 

In contrast to the aforementioned fullerenes, C76 is a chiral molecule containing 30 different types of carbon-carbon bond. In this molecule five different pyracylene-type carbon-carbon bonds repeat to form chrysene-shaped units. Kinetic resolution of this fullerene has been achieved via asymmetric osmylation in the presence of a cinchona based chiral ligand (see Section 4.4.4.1.1., ligand 1 d/2 d, Table 5). The calculated enantiomeric excess of the recovered material (after 95% conversion) is >97%, whereas the regenerated C76, formed by tin(II) chloride reduction of the osmylated material (after 33 % conversion), is enriched in the opposite enantiomer. Analysis of the local curvature of the C76 molecule indicates that Os04 should selectively add to two of the 30 types of bonds86. 

The study of the origin of the high enantioselectivity shown by the cinchona based asymmetric catalytic dihydroxylation, and especially by the bis-armed ligands (1/2f, g, h, and i), is a subject of current interest18. 

Besides the above mentioned cinchona based system, to date only a few nitrogen-based chiral ligands have been reported to work under catalytic conditions70-72. The C2-symmetrical l,4-diazabicyclo[2.2.2]octane (DABCO) derivative l70 and the isoxazolidines 2 and 371 are examples. The main problem with most of the other amines tested stems from the formation of ligand-osmate ester complexes which are too stable. Although with these ligands the levels of enantiomeric excess are still not satisfactory, the successful osmium turnover gives hope for future improvements. 

The scope of cinchona-based chiral auxiliary or chirality transmitters for enantioselective reductions is at the moment restricted to heterogeneous Pt and Pd catalysts and primarily to the reduction of a-functionalized ketones and to a lesser degree of activated C=C bonds. Up to now, very few homogeneous catalysts have been described, and with the exception of a transfer hydrogenation system, none shows any promise. 

Cinchona-Based Chiral Ligands in C— F Bond Forming Reactions I 99... 

Cinchona-Based Organocatalysts for Asymmetric Oxidations and Reductions... 

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

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