Enantiomeric excess value

The enantiomeric excess values of the (S)-cyanohydrins are obtained from the ( + )-(R)-Mosher ester derivatives [a-methoxy-a-(trifluoromethyl)phenylacetates], whereas the corresponding benzeneacetic acids are first converted into their isopropyl carboxylates which then yield the ( + )-(ft)-Mosher ester derivatives. 

However, considering practical limitations, that is, the availability of optically pure enantiomers, E values are more commonly determined on racemates by evaluating the enantiomeric excess values as a function of the extent of conversion in batch reactions. For irreversible reactions, the E value can be calculated from Equation 1 (when the enantiomeric excess ofthe product is known) or from Equation 2 (when the enantiomeric excess ofthe substrate is knovm) [la]. For reversible reactions, which may be the case in enzymatic resolution carried out in organic solvents (especially at extents of conversion higher than 40%), Equations 3 or 4, in which the reaction equilibrium constant has been introduced, should be used [lb]. 

The original library of 10 000 clones used in the Baeyer-Villiger reaction [89] was screened for performance as potential catalysts in the sulfoxidation [32]. This led to the discovery of at least 20 mutants having enantiomeric excess values in the range of 85-99%, some being (R) selective and others being (S) selective. Five mutants resulting in enantiomeric excess values of >95% were sequenced (Table 2.2) [32]. 

For reduction of acetylenic ketones, two oxidoreductases were used [25]. Lactobacillus brevis alcohol dehydrogenase (LBADH) gave the (R)-alcohols and Candida parapsilosis carbonyl reductase (CPCR) afforded the (S)-isomer, both in good yield and excellent enantioselectivity. By changing the steric demand of the substituents, the enantiomeric excess values can be adjusted and even the configurations of the products can be altered (Figure 8.34). 

The dynamic resolution of an aldehyde is shown in Figure 8.40. The racemization of starting aldehyde and enantioselective reduction of carbonyl group by baker s yeast resulted in the formation of chiral carbon centers. The enantiomeric excess value of the product was improved from 19 to 90% by changing the ester moiety from the isopropyl group to the neopentyl group [30a]. 

Products 21 and 22 obtained in this reaction differ in their ESI-MS spectra, and the difference in the abundance of respective signals can be expressed quantitatively. Studies have shown that the pseudo-enantiomeric-excess values obtained in this way are in agreement 5% with the data obtained by chromatographic methods, which is sufficient for studying relative values and choosing most selective mutants. 

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

The enantiomeric ratio is an intrinsic feature of enzyme-enantiomer couples. The actual realization of this property in a resolution reaction affects the enantiomeric excess value, ees (for the substrate) and eeP (for the product) (Equation 3) ... 

Chiral PCPs can be used for heterogeneous asymmetric catalysis.43,52 162 164 167 The chiral porous ZrIV phosphonate with Run-binap fragments (binap = 2,2 -bis(diphenylphosphanyl)-1,1 -binaphthyl) has a permanent porosity, and shows asymmetric catalytic activity in the hydrogenation of (3-keto esters with enantiomeric excess values of up to 95%.162... 

Asymmetric Hydrogenation of a, p- Unsaturated Carboxylic Acids A Comparison of Product Percent Enantiomeric Excess Values for Several Ligandsa c... 

Asymmetric photodestruction can be used as a method to achieve high enantiomeric excess values. As the g factors are generally small, this is only reached at a large where, according to Fig. 5, most of the starting material has disappeared. So Fig. 6 in some way is deceptive. The optical yield in reference to the starting material can be defined by... 

Interestingly, hydrolase-type enzymes could also be employed for enantioselective hydrations79. Yields and enantiomeric excess values obtained in the addition of water to 2-(trifluo-romethyl)propenoic acid (7) are summarized. Unfortunately, the absolute configuration of the product 8 was not determined, the enantiomeric excess values stated rest on 19F-NMR analysis of the Mosher ester. Whereas ethanol and phenol did not react under these conditions, the /V-nucleophiles diethylamine and aniline, and also thiophenol, could be added to 7 in moderate to good yields and enantiomeric excess values. Finally, the bifunctional aniline derivatives 9 afforded the lactams 10 in 52-90% yield and 25-67% ee. Again, the absolute configurations of the products were not determined. 

Generally, the use of a catalyst containing a -hydroxy amine moiety, for example, cinchona and ephedra alkaloids or 4-(4-aminophenylmethyl)-l-ethyl-2-pyrrolidinol, gives addition products with higher optical purity or enantiomeric excess values (up to 88%). The use of polar solvents, concentrated reaction solutions and the presence of tetrabutylammonium salts can substantially lower the optical purity of the products88. 

Nonracemic, axially stereogenic allylamine 8 is obtained by palladium(0)-catalyzed allylic substitution of meso-diastereomers 7 with morpholine using (S,S)-Diop (D)62. From both substrates, the product 8 displays an optical rotation unequal to zero. The corresponding enantiomeric excess values have not been determined. 

Oxidation of the lithium enolate of 1-tetralone 23 to (—)-2-hydroxy-l-tetralone 24, the AB ring synthon of the antitumour antibiotic rhodomycinones, with (+)-18 (X = OMe, Y = H, equation 10) resulted in much better enantiomeric excess values (ee >94%) than hydroxylation with other oxaridines. ... 

As in the Jones protocol the cubic section model of the substrate binding domain of HLADH were constructed using structures of alcohol products rather than ketone substrates. The alcohol products were originally chosen by the Jones group because the transition state the geometry for the reduction was considered to resemble that of the alcohol rather than that of the ketone. The relative rate of reduction of substrate vs cyclohexanone for each ketone was required to be known. Furthermore, configurations of alcohol products, enantiomeric excess values, yields and % conversion of substrate required for calculation of the priority number for each enantiomer of product should be measured under comparable conditions (i.e. pH, temperature, concentration of enzyme, coenzyme and substrate, etc.). According to Alderweireldt et al. (1988) HLADH models are valid only for reaction conditions used in the reactions from which the models are constructed. Furthermore, the model is oniy reliable if the reactions have been conducted under kinetic control. 

Using these criteria 45 substrates for which experimental information was available for reaction at pH 7 were chosen to construct the model (Table 3). There is a significant amount of literature data for substrates of HLADH which lack information on enantiomeric excess values and absolute configurations of products and where the relative rates of reaction have been measured under different reaction conditions (e.g. pH 8.5). Substrates falling into this category (46-69, Table 4) were not used. Heterocyclic bicyclic substrates 70-73 were only used for testing. 

Reactions exhibiting diastereofacial selectivity, which occur when the imine or the enolate contains an endogenous stereocenter or a chiral auxiliary, have important applications for the synthesis of optically active 3-l ctams and 3-amino carboxylic acid derivatives. Early work by Furukawa et al. has demonstrated the viability of preparing optically active 3-amino acids from chiral imines. For example, the Schiff base derived from (5)-a-methylbenzylamine (110) reacts with Reformatsky reagent (111) to give, after hydrolysis and removal of the chiral auxiliary, 3-amino-2,2-dimethyl-3-phenylpropionic acid (112) in 33% ee (Scheme 21). Similar Reformatsky reactions have been performed using (-)-menthyl esters but the enantiomeric excess values are lower. ... 

The early good results obtained by the hydroformylation of styrene with platinum(II) chloride/tin(II) chloride in the presence of chiral phosphanes (Diop and DIPHOL)138 have been reevaluated51. It has been found that enantiomeric excess values based on optical measurements in solution cannot be correlated with rotational values of the neat compound, since rotation in solution is considerably higher. Thus, the enantiomeric excess values originally reported (95% 138), have to be corrected to 73%47. Variation of reaction conditions still leads to inductions of up to 80% ee using the same catalysts and ligands47. 

The analogous 3-ethyl-3-phenyl-4-pentcnal can also be converted to an optically active cy-clopcntanone product, but here no enantiomeric excess values are available75 76. Decarbony-lation byproducts are also observed, those from 2-methyl-2-phenyl-4-pentenal appear as ( )-and (Z)-2-phenyl-2-pentene75 76. 

The reduction of nitroolefins is also possible using other microbial systems. In a microbial screening20 good reducing strains were found among actinomycetes belonging to Rhodococcus, Nocardia and Mycobacterium. The yield is comparable to the results obtained with yeast, however, the enantiomeric excess values remained low due to spontaneous racemization of the products. 

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