Racemic compounds alcohols

Racemate resolution, 1, 2 Racemic compounds alcohols, 45 chirally labile, 75 computer simulation, 79 diphosphines, 26 dynamic resolution, 75 esters, 309... 

It is well known that certain microorganisms are able to effect the deracemization of racemic secondary alcohols with a high yield of enantiomerically enriched compounds. These deracemization processes often involve two different alcohol dehydrogenases with complementary enantiospedficity. In this context Porto ef al. [24] have shown that various fungi, induding Aspergillus terreus CCT 3320 and A. terreus CCT 4083, are able to deracemize ortho- and meta-fluorophenyl-l-ethanol in good... 

C-chiral hydroxy phosphorus derivatives, which have been described so far in the literature, are secondary alcohols. Thus, the syntheses of non-racemic compounds of this type comprise two main approaches (cf. C-chiral hydroxyalkyl sulfones. Section 2.2) asymmetric reduction of the corresponding keto derivatives and resolution of racemic hydroxyalkanephosphorus substrates. 

Scheme 20.4 Possible pathways of hydrogen transfer during the racemizations of alcohols using the corresponding carbonyl compound and a hydrogen transfer catalyst.

Relatively little attention has been paid to the conversion of racemic compounds into their enantiomerically pure versions in a single process, in other words a deracemization. For certain classes of chiral compounds such as secondary alcohols, this approach should provide many benefits, particularly to the pharmaceutical industry. Existing routes to high value intermediates in their racemic form may be modified to provide the equivalent homochiral product, thus reducing the extent of development chemistry required. In addition, the... 

As described in the section dealing with liquid chromatographic methods, the reaction of 0,0-di-substituted tartaric anhydrides with racemic amino alcohols in acidic solution leads exclusively to the corresponding diastereomeric monoesters, which are easily separated by reversed-phase HPLC. However, H- and sometimes 13C-NMR spectra of these compounds are in many cases also highly useful for determining the diastereomeric ratio and in many cases the absolute configuration. 

The polymer of high molecular weight in the solid stage exhibited high crystallinity under a polarized microscope and insoluble in common organic solvents. When the polymer with high optical rotation was used as stationary phase or sorbent for the chromatographic resolution of racemic compounds, it showed the ability of resolution for many kinds of compounds, such as alcohols, amines, esters, and even hydrocarbons (28). 

Resolution of a racemic compound, 503 of Mc.-octyl alcohol, 505 P-Reeorcylaldehyde, 690,702 P Reeorcylie acid, 754, 775 Rimmi test, 420 ... 

This method is particularly effective with cyclic substrates, and the combined effects of intramolecular and intermolecular asymmetric induction give up to 76 1 (kf/ks) differentiation between enantiomers of a cyclic allylic alcohol. This kinetic resolution provides a practical method to resolve 4-hydroxy-2-cyclopentenone, a readily available but sensitive compound. Hydrogenation of the racemic compound at 4 atm H2 proceeds with kf/ks =11, and, at 68% conversion, gives the slow-reacting R enantiomer in 98% ee. The alcoholic product is readily convertible to its crystalline, enantiomerically pure fert-butyldimethylsilyl ether, an important building block in the three-component coupling synthesis of prostaglandins (67). 

The combination of Ru complex-catalyzed stereomutation of secondary alcohols with enzyme-catalyzed enantioselective acylation is an efficient procedure to obtain chiral acyloxy compounds with excellent optical purity from a variety of racemic secondary alcohols via dynamic kinetic resolution [112]. 

But very little is known of the receptor s south end, so to speak, the geometry of the area where the opposite end of the molecule has to fit. Here, with 2-C-17, there is a secondary butyl group, and this contains an asymmetric carbon atom. But now this center of asymmetry is clear across the benzene ring from the nitrogen, and should certainly be in some entirely new part of the receptor site. Why not make this compound with the R and the S forms in this new and unusual location Why not, indeed Why not call them the right-lane and the left lane of the Nimitz Fortunately, both R and S secondary butyl alcohols were easily obtained, and the synthesis given above for the racemic compound was paralleled for each of these isomers, separately. Is there any chemistry that is different with the specific optical isomers from that which has been reported with the racemic There certainly is for the first step, since the butyl alcohols rather than the butyl bromides must be used, and this first step must go by inversion, and it cannot be allowed any racemization (loss of the optical purity of the chiral center). 

Enzymatic resolution of racemic secondary alcohols by enantiomer-selective acylation gives optically pure compounds with up to 50% yield [332], When this method is coupled with the principle of dynamic kinetic resolution (see Section 1.4.1.5), the theoretical yield increases to 100%. Thus a reaction system consisting of an achiral transition-metal catalyst for racemization, a suitable enzyme, acetophenone, and an acetyl donor allows the transformation of racemic 1-phenylethanol to the R acetates with an excellent ee (Scheme 1.93) [333]. The presence of one equiv. of acetophenone is necessary to promote the alcohol racemization catalyzed by the... 

Machida et al. presented a method for the immobilization of CCE on silica gel in 1998 [45]. They reported the covalent binding of (+)-(18-crown-6)-tetracarboxylic acid to 3-aminopropylsilanized silica gel and the prepared CSP was tested to separate enantiomers of amino acids, amino alcohols and other drugs (containing primary amino group). In 1998, the same CSP was prepared by Hyun et al. [46]. The developed CSP was used extensively for the chiral resolution of a variety of racemic compounds having a primary amino group... 

In 1998, Machida et al. [45] and Hyun et al. [46] developed a new CCE-based CSP (covalently bonded to silica gel see Sect. 8.2). This CSP was used successfully for the chiral resolution of certain racemic compounds using a variety of mobile phases. The most important applications of this CSP are for the resolution of amino acids, amino esters, amino alcohols, amines, amides, quinolone antibacterials, and other drugs having primary amino groups [46-51,64,65]. The typical chromatograms of the chiral resolution of amino acids on (+)-(18-crown-6)-2,3,ll,12-tetracarboxylic acid CSP are shown in Figure 4. The enantiomeric resolution of the racemic compound on CCE-based CSPs are listed in Table 2. There is no report available on the chiral separations at the preparative scale using these CSPs. 

Because the steric effect contributes to the complex formation between guest and host, the chiral resolution on these CSPs is affected by the structures of the analytes. Amino acids, amino alcohols, and derivatives of amines are the best classes for studying the effect of analyte structures on the chiral resolution. The effect of analyte structures on the chiral resolution may be obtained from the work of Hyun et al. [47,48]. The authors studied the chiral resolution of amino alcohols, amides, amino esters, and amino carbonyls. The effects of the substituents on the chiral resolution of some racemic compounds are shown in Table 6. A perusal of this table indicates the dominant effect of steric interactions on chiral resolution. Furthermore, an improved resolution of the racemic compounds, having phenyl moieties as the substituents, may be observed from this Table 6. ft may be the result of the presence of n—n interactions between the CCE and racemates. Generally, the resolution decreases with the addition of bulky groups, which may be caused by the steric effects. In addition, some anions have been used as the mobile phase additives for the improvement of the chiral resolution of amino acids [76]. Recently, Machida et al. [69] reported the use of some mobile phase additives for the improvement of chiral resolution. They observed an improvement in the chiral resolution of some hydrophobic amino compound using cyclodextrins and cations as mobile phase additives. 

Many of the chiral molecules containing amide groups were bonded to a solid support for the preparation of CSPs [16-19]. The racemic compounds resolved on these CSPs include a-hydroxycarbonyls, /i-hydroxycarbonyls, amino acids, amino alcohols, amine, and derivatized and underivatized diols. The preliminary chiral diamide phase [(/V-foriuyl-L-valyl)aminopropyl)silica gel] has sufficient separability for racemic /Y-acylatcd a-amino acid esters but not in other types of enantiomer [16]. Most of the eluents used with these CSPs are of normal phase mode, including w-hcxanc, 2-propanol, chlorinated organic solvents, and acetonitrile. 

Blaschke et al. [54—56] synthesized polyacrylamide and polymethacrylamide containing chiral side chains. In order to make CSPs, these polymers were bonded to silica gel chemically [54-56]. The CSP obtained by /V-acrylol-(.S)-phenylalanine ethyl ester was commercialized by Merck Chemical Company by the trade name ChiraSpher. The racemic compounds resolved are those capable of forming hydrogen-bondings (i.e., amides, imides, carboxylic acids, and alcohols). It has been reported that nonpolar solvents like benzene and toluene individually or their mixtures were the best mobile phases. In addition to these CSPs, other amide CSPs were prepared and tested for the chiral resolution [57,58]. 

High enantiomeric excess in organocatalytic desymmetrization of meso-diols using chiral phosphines as nucleophilic catalysts was achieved for the first time by Vedejs et al. (Scheme 13.21) [36a], In this approach selectivity factors up to 5.5 were achieved when the C2-symmetric phospholane 42a was employed (application of chiral phosphines in the kinetic resolution of racemic secondary alcohols is discussed in Section 12.1). A later study compared the performance of the phos-pholanes 42b-d with that of the phosphabicyclooctanes 43a-c in the desymmetrization of meso-hydrobenzoin (Scheme 13.21) [36b], Improved enantioselectivity was observed for phospholanes 42b-d (86% for 42c) but reactions were usually slow. Currently the bicyclic compound 43a seems to be the best compromise between catalyst accessibility, reactivity, and enantioselectivity - the monobenzoate of hydrobenzoin has been obtained with a yield of 97% and up to 94% ee [36b]. 

Chiral fluorinated compounds have been also synthesized due to the increasing attentions on the unique physical and biological features induced by fluorine atoms. Therefore, various racemic fluorinated alcohols were optically resolved (Figure 15).15... 

Novel approach for optically pure alcohol from racemic compounds is the use of dehalogenases.24 For example, L-2-halo acid dehalogenase Pseudomonas putida was used for the synthesis of D-3-chlorolactic acid from racemic 2,3-dichloropropionic acid (Figure 23(a)).24ad The enzyme catalyzed hydrolytic release of halogen from 2-halocarboxylic acids and produces 2-hydroxy acids with inversion of the configuration. L-2-Halo acid dehalogenase acted on the L-isomer of 2-halo acids and produces D-2-hydroxy acid with an excellent enantioselectivity. 

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