Enantiomer discrimination

In the hydrogenation of 3-substituted itaconate ester derivatives by rhodium-dipamp, the alkoxycarbonyl group at the stereogenic center also exerts a powerful directing effect, comparable to that induced by OH in the kinetic resolution of (a-hydroxyethyl)acrylate, leading to a high enantiomer-discriminating ability up to feR fes = 16 1 (Table 21.18, entry 5) [64]. 

Kinetic resolution results of ketone and imine derivatives are indicated in Table 21.19. In the kinetic resolution of cyclic ketones or keto esters, ruthenium atrop-isomeric diphosphine catalysts 25 induced high enantiomer-discriminating ability, and high enantiopurity is realized at near 50% conversion [116, 117]. In the case of a bicyclic keto ester, the presence of hydrogen chloride in methanol served to raise the enantiomer-discriminating ability of the Ru-binap catalyst (entry 1) [116]. 

Figure 14. Filins of L-and Dj.-AT-stearoylleucine no enantiomer discrimination is discernible. From Zeelen (84).

In her initial investigation, Lundquist studied the monolayer behavior of racemic and optically active forms of both tetracosan-2-ol and its acetate derivative on 0.0 lA aqueous HCl over a considerable range of temperature (77). In each case, it was possible to demonstrate chiral discrimination between pure enantiomers versus the racemic substance. Furthermore, the extent of enantiomer discrimination was significantly temperature dependent, being enhanced at lower temperatures and frequently disappearing at higher ones. Under favorable conditions of temperature, however, the appearance of the force-area curves could be very sensitive to the optical purity... 

A genuine example of enantiomer discrimination has been reported for polypeptides by Malcolm (108,109). Mixed monolayers of enantiomerically related samples of isotactic poly (alanine), poly(7-benzylglutamate), poly(/3-benzylaspartate), and poly(e-benzyloxycarbonyllysine) were studied to shed some light on the... 

Meanwhile, a wide variety of cinchona alkaloid derivatives have been systematically developed as chiral selectors, which complement each other in their enantiomer discrimination profiles. Considering the variety of derivatives, an overall reasonably broad applicability spectrum, approximating for chiral acids a 100% success rate, is yielded and extreme enantiorecognition levels (a-values above 15) could be realized for some chiral solutes with certain selectors. Moreover, various studies carried out with the CHIRALPAK QD/QN-AX columns in industry and academia clearly document their practical usefulness for solving challenging real-life problems and this should be illustrated by the present review article as well. 

Complete enantiomer discrimination and asymmetric deactivation of the racemic XylBINAP-RuCl2(dmf) ( )-7b using DM-DABN as a chiral poison are shown to be effective in the kinetic resolution of 2-cyclohexenol (Scheme 8.9). Use of just a 0.5 molar amount of (5)-DM-DABN relative to ( )-7b gives enantiopure (S)-2-cyclohexenol, which is kinetically resolved in the same conversion as enantiopure 7b. Indeed, the relative rate of hydrogenation of (R)- versus (5)-2-cyclohexenol in the presence of only a 0.5 molar amount of (5)-DM-DABN relative to ( )-7b is significantly large (kf/kg = 102). The combination of ( )-7b with (S)-DM-DABN also gives 99.3% ee of (R)-methyl 3-hydroxybutanoate quantitatively... 

Aqueous surfactants are another class of catalysts. Substantial rate enhancement is seen in the reaction occurring at the micellar hydrocarbon-water interface, which is ascribed to a concentration of the reactant in the micellar pseudo-phase. Chiral p-nitrophenyl esters derived from phenylalanine are hydrolyzed by a histidine-containing dipeptide at a micellar interphase, at which a very high enantiomer discrimination, kR/ks up to 30.4 at 0°C, is observed (49). As shown in Scheme 20, the enantioselectivity is expressed at the stage at which a transient, zwitter-ionic tetrahedral intermediate leading to the acylimidazole is formed,... 

An interesting approach to translating remote chirality into enantiomer discrimination relies upon blocking one face of the heterocycle using axially chiral DMAP analogs. To this end, Spivey and co-workers have examined catalysts 39 and 40, obtained in optically pure form by preparative HPLC [38]. Catalyst 39 is effective for the kinetic resolution of aryl alkyl carbinols with good selec-tivities (krei=8.4-27, see Scheme 7). The substitution on the 4-position nitrogen... 

The same transition-state model can be used to correlate the results for the enantioface-discriminating hydrocarbalkoxylation discussed above with the few results obtained in the enantiomer-discriminating hydrocarbalkoxylation, as will be discussed elsewhere (32). 

Asymmetric hydroformylations of all the above types have been achieved with rhodium catalysts enantioface- and enantiomer-discriminating hydroformylations also occur with cobalt and platinum catalysts whereas with ruthenium or iridium complexes only enantioface-discriminating synthesis has been reported up to now (see Sect. 2.1.4.). 

When more than one isomer is formed during the reaction an enantiomer discrimination can take place also with quantitative transformation of the substrate (Scheme 1, reaction 4). This is the case in the hydroformylation of 3-phenyl-1-butene with a Rh/(—)-DIOP catalytic system 14) where 4-phenylpentanal arises preferentially... 

In all examples available, geometrically similar antipodes react preferentially in the case of mono- and di-substituted ethylenes respectively, the three exceptions in Table 5 being due to the fact that substrates with similar geometry have different notations (Fig. 5). No observable kinetic resolution is achieved in the platinum-catalyzed hydroformylation of 3-methyl-1-pentene whereas a slight enantiomer discrimination is observed in the case of 2,4-dimethyl-1-pentene. 

Using the same model and considering the results of the investigation of square planar platinum(II)-chiral olefin complexes 61-63> it is possible to correlate enantio-face discriminating hydroformylation with enantiomer discriminating hydroformy-lation. 

Table 14. Correlation between enantioface-discriminating and enantiomer-discriminating hydroformylation with Rh/(—)-DIOP catalytic systems"...

PBP sequenced AF031492 nearly identical to A. osakana PBP no enantiomer discrimination (Wojtasek et al. 1998)... 

Kiaholz, B.P., Mitschler, A., Belema, M., Zusi, C., Moras, D. Enantiomer discrimination illustrated by high-resolution crystal structures of the human nuclear receptor hRARgamma. PNAS 2000, 97, 6322-6327. 

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