Optically active products chiral resolution

In the kinetic resolution, the yield of desired optically active product cannot exceed 50% based on the racemic substrate, even if the chiral-discriminating ability of the chiral catalyst is extremely high. In order to obtain one diastereomer selectively, the conversion must be suppressed to less than 50%, while in order to obtain one enantiomer of the starting material selectively, a higher than 50% conversion is required. If the stereogenic center is labile in the racemic substrate, one can convert the substrate completely to gain almost 100% yield of the diastereomer formation by utilizing dynamic stereomutation. 

There are two possible approaches for the preparation of optically active products by chemical transformation of optically inactive starting materials kinetic resolution and asymmetric synthesis [44,87], For both types of reactions there is one principle in order to make an optically active compound we need another optically active compound. A kinetic resolution depends on the fact that two enantiomers of a racemate react at different rates with a chiral reagent or catalyst. Accordingly, an asymmetric synthesis involves the creation of an asymmetric center that occurs by chiral discrimination of equivalent groups in an achiral starting material. This can be done either by enan-tioselective (which involves the reaction of a prochiral molecule with a chiral substance) or diastereoselective (which involves the preferential formation of a single diastereomer by the creation of a new asymmetric center in a chiral molecule) synthesis. 

Problem 5.23 Answer True or False to each of the following statements and explain your choice. ( ) There are two broad classes of stereoisomers, (b) Achiral molecules cannot possess chiral centers, (c) A reaction catalyzed by an enzyme always gives an optically active product, (d) Racemization of an enantiomer must result in the breaking of at least one bond to the chiral center, (e) An attempted resolution can distinguish a racemate from a meso compound. <... 

A measure of the interest in the biological activity of these dibenzyl-butyrolactone lignans is evinced in the recent spate of publications dealing with the total synthesis of the natural optically active products. Again, the Stobbe condensation pathway (Scheme 9) has been usefully exploited for this purpose. In a series of papers, resolution of the intermediate hemisuccinate esters (433 by chiral bases has been described (54), as has asymmetric hydrogenation (55), and the optically active lignan products synthesized in the usual way (42 - 44 45). 

Unless a resolution step is included, the a-amino acids prepared by the synthetic methods just described are racemic. Optically active amino acids, when desired, may be obtained by resolving a racemic mixture or by enantioselective synthesis. A synthesis is described as enantioselective if it produces one enantiomer of a chiral compound in an amount greater than its mirror image. Recall from Section 7.9 that optically inactive reactants cannot give optically active products. Enantioselective syntheses of amino acids therefore require an enantiomerically enriched chiral reagent or catalyst at some point in... 

Last but not least, all enzymes are made from L-amino acids and thus are chiral catalysts. As a consequence, any type of chirality present in the substrate molecule is recognized upon formation of the enzyme-substrate complex. Thus, a prochiral substrate may be transformed into an optically active product through a desymmetrization process and both enantiomers of a racemic substrate usually react at different rates, affording a kinetic resolution. 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

Catalytic kinetic resolution can be the method of choice for the preparation of enantioenriched materials, particularly when the racemate is inexpensive and readily available and direct asymmetric routes to the optically active compounds are lacking. However, several other criteria-induding catalyst selectivity, efficiency, and cost, stoichiometric reagent cost, waste generation, volumetric throughput, ease of product isolation, scalability, and the existence of viable alternatives from the chiral pool (or classical resolution)-must be taken into consideration as well... 

C-chiral racemic y-hydroxy sulfides were also resolved using PEL under kinetic resolution conditions. The products were transformed into optically active 3-(alkanesulfonyloxy)thiolane salts (Scheme 1). Similarly, 1,2-cyclic sulfite glycerol derivatives cis and trans) were resolved into enantiomers via a Pseudomonas cepacia-catalysed acylation with vinyl butyrate. The E values depended on the solvent used and varied from 2 to 26. ... 

Chiral 1,1 -binaphthol derivatives are well established as readily available chiral catalysts and auxiliaries for the production of various useful optically active compounds. Tanabe et al. investigated [11] a crystalline-liquid resolution of (1R) -// . v - c h rysanthemic acid utilizing l,l -binaphthyl monoethyl ether (25) (Scheme 3). 

The enantioselective oxidative coupling of 2-naphthol itself was achieved by the aerobic oxidative reaction catalyzed by the photoactivated chiral ruthenium(II)-salen complex 73. 2 it reported that the (/ ,/ )-chloronitrosyl(salen)ruthenium complex [(/ ,/ )-(NO)Ru(II)salen complex] effectively catalyzed the aerobic oxidation of racemic secondary alcohols in a kinetic resolution manner under visible-light irradiation. The reaction mechanism is not fully understood although the electron transfer process should be involved. The solution of 2-naphthol was stirred in air under irradiation by a halogen lamp at 25°C for 24 h to afford BINOL 66 as the sole product. The screening of various chiral diamines and binaphthyl chirality revealed that the binaphthyl unit influences the enantioselection in this coupling reaction. The combination of (/f,f )-cyclohexanediamine and the (R)-binaphthyl unit was found to construct the most matched hgand to obtain the optically active BINOL 66 in 65% ee. 

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 synthesis of optically active polymers was tackled with the purpose not only of clarifying the mechanism of polymerization and the conformational state of polymers in solution, but also to explore the potential of these products in many fields as chiral catalysts, as stationary phases for chromatographic resolution of optical antipodes, for the preparation of liquid crystals, and so on. 

Another approach that relies on asymmetric induction from the alkene part, uses chiral auxiliaries of various types, thereby leading to enantiomerically enriched or pure isoxazoline products. The complexity of some of these auxiliaries is high, and more economical solutions are desirable since the competition is the resolution of racemic cycloadducts with an overall efficiency up to 50% yield. With chiral nitrile oxides, the situation is much less satisfactory since asymmetric induction of the 1,4-type (with 1-alkenes) is minimal, and hardly better with a 1,3-relationship of inducing-forming stereocenters, when 1,2-disubstituted alkenes are employed (Scheme 6.22). Upon separation of the two diastereomers, however, another entry to pure optically active isoxazolines is available. 

---