Cinchona functional groups

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

Cinchona alkaloids now occupy the central position in designing the chiral non-racemic phase transfer catalysts because they have various functional groups easily derivatized and are commercially available with cheap price. The quaternary ammonium salts derived from cinchona alkaloids as well as some other phase transfer catalysts are... 

Fourier transform-infrared (FT-IR) spectroscopic studies on SO-SA complexation provides information that may be complementary to that of NMR and other techniques, namely, in particular, on the involvement of functional groups in intermolecular and intramolecular interactions. Attenuated total reflectance (ATR) IR spectroscopy has been used for the study of binding modes of cinchona alkaloid selectors either in solution [95] or in solid state [94], or directly on the CSP [96]. 

Using the addition of dimethyl malonate to nitro-olefms as the model reaction, Connon et al. [72] in 2(X)5 reported a highly functionahzed Cinchona alkaloid-derived chiral thiourea. Key functional groups were identified to enhance the catalyst s stereodirecting properties. Aside from the advantage of a bifunctional Cinchona alkaloid... 

During the search for the optimal dimeric PTC for this epoxidation, the Park-Jew group found an interesting result, namely that the functional groups of 9-0 H and 6 -OMe in the cinchona unit, along with 2-F group in the phenyl linker, were critical factors for high enantioselectivity of the reaction (Scheme 4.16). 

To remove the feedback regulation mechanism and to avoid product degradation various adsorbents have been used for the in situ separation of plant cell cultures as shown in Table 1. In situ removal with polymeric adsorbents stimulated anthraquinone production more than the adsorbent-free control in Cinchona ledgeriana cells [35]. It was found that nonionic polymeric resins such as Amberlite XAD-2 and XAD-4 without specific functional groups are suitable for the adsorption of plant metabolite [36]. The use of the natural polymeric resin XAD-4 for the recovery of indole alkaloids showed that this resin could concentrate the alkaloids ajmalicine by two orders of magnitude over solvent extraction [37] but the adsorption by this resin proved to be relatively nonspecific. A more specific selectivity would be beneficial because plant cells produce a large number of biosynthetically related products and the purification of a several chemically similar solutes mixture is difficult [16]. 

The cinchona alkaloids have opened up the field of asymmetric oxidations of alkenes without the need for a functional group within the substrate to form a complex with the metal. Current methodology is limited to osmium-based oxidations. The power of the asymmetric dihydroxylation reaction is exemplified by the thousands (literally) of examples for the use of this reaction to establish stereogenic centers in target molecule synthesis. The usefulness of the AD reaction is augmented by the bountiful chemistry of cyclic sulfates and sulfites derived from the resultant 1,2-diols. 

The asymmetric phase-transfer epoxidation of ( )-a, 3-unsaturated sulfones has recently been achieved by Dorow and coworker using N-anthracenylmethyl cinchona alkaloid derivatives as catalysts and KOC1 as an oxidant at low temperature [23]. The screening of several etheral functional groups at the C9( O) position of the catalyst moiety indicated that the steric size and the electronic factor of the ether substituent has a significant effect on both the reaction conversion and the enantioselectivity. 

Several new syntheses of quinoline and indole Cinchona alkaloids were reported in the last few years. In these synthetic routes the quinuclidine moiety of the alkaloids was derived from various synthetic meroquinene derivatives 18. These new syntheses all proceed through intermediates of general formula 19 which are characterized by a properly positioned functional group (t.e., X) which facilitates the formation of quinuclidine ring 20. 

Pd modified by cinchona, vinca, or ephedra alkaloids is a moderately efficient catalyst but Pd is still the catalyst of choice for the enantioselective hydrogenation of olefins with a functional group in the a position [8,20]. Modification of Pd with cinchonidine is as simple as for Pt, but Pd requires a considerably lower substrate/ modifier ratio than Pt, probably because of weaker adsorption and/or partial degradation (hydrogenation) of the modifier during reaction. Another drawback is that the reactions are not accelerated but decelerated by the chiral modifier (by a factor of up to 140 [21]). This phenomenon can rationalize the moderate performance of chirally modified Pd. 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

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