Optically-active compounds, preparation

All of the optically active compounds prepared by diastereoisomer separation and/or conversion to enantiomers have proved to be configurationally stable at the metal center as long as they are in the solid state. Concerning their behavior in solution, however, the optically active or-gano-transition-metal compounds are divided into two groups (a) compounds configurationally stable at the metal center, which do not racem-ize or epimerize with respect to the metal atom prior to decomposition and (b) compounds configurationally labile at the metal center which racemize or epimerize with respect to the metal atom prior to decomposition. 

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... 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

Although decarboxylation reaction seems to be a simple one-carbon removing reaction, it is demonstrated that this reaction is a unique and useful reaction in the preparation of optically active carboxylic acids. If the starting material is a racemic carboxylic acid, the optically active compound can be obtained via symmetrization by chemical carboxylation followed by asymmetrization via enzymatic reaction. Accordingly, the whole process can be said as chemicoenzymatic deracemization (Fig. 24). 

The standard work of Evans [2] as well as a survey of the papers produced in the Journal of Labeled Compounds and Radiopharmaceuticals over the last 20 years shows that the main tritiation routes are as given in Tab. 13.1. One can immediately see that unlike most 14C-labeling routes they consist of one step and frequently involve a catalyst, which can be either homogeneous or heterogeneous. One should therefore be able to exploit the tremendous developments that have been made in catalysis in recent years to benefit tritiation procedures. Chirally catalyzed hydrogenation reactions (Knowles and Noyori were recently awarded the Nobel prize for chemistry for their work in this area, sharing it with Sharpless for his work on the equivalent oxidation reactions) immediately come to mind. Already optically active compounds such as tritiated 1-alanine, 1-tyrosine, 1-dopa, etc. have been prepared in this way. 

For general application of these chiral ligands, see (a) Kagan, H. B. Chiral Ligands for Asymmetric Catalysis in Morrison, J. D. ed. Asymmetric Synthesis, vol. 5, Chap. 1, Academic Press, New York, 1985. (b) Kagan, H. B., Sasaki, M. Optically Active Phosphines Preparation, Uses and Chiroptical Properties in Hartley, F. R. ed. The Chemistry of Organo Phosphorous Compounds, John Wiley Sons, New York, 1990, vol. 1, Chap. 3. 

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. 

Therefore, as we have seen, we can not prepare an optically active compound from an inactive one by the ordinary laboratory methods. Such a synthesis however, can be accomplished by attaching an optically active molecule or groups to the original compound and then removing it after the new asymmetric atom has been produced. 

In Chapter 9 we have already referred to the paramount importance of enantioselective syntheses for the preparation of optically active compounds. 

Finally, after a brief look at the structure and mechanism of action of enzymes, most of the chapter will be devoted to the innovative and promising field of catalytic antibodies or abzymes, which will probably be the method of choice for preparing optically active compounds in the future. 

Other transition metal anions fail in giving the expected compounds . Germanium halides react more easily but are useless for the preparation of optically active compounds. Indeed, optically active bromo-germanes are not known, and chlorogermanes rapidly racemize in ether or tetrahydrofuran. ... 

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... 

In this enzymatic transformation, three optically active compounds were prepared in one step. Besides the enantiomerically enriched hydroperoxide (5)-16/17a, also the opposite enantiomer of the corresponding alcohol (/f)-19/18a and enantiomerically enriched (S)-sulfoxide 23 could be isolated (equation 13). 

Enzymes are widely recognized as valuable tools for the synthesis of optically active compounds [22]. Thus, lipase-catalyzed acylation or deacylation is one of the most efficient methods for the preparation of optically active alcohols, acids, and esters. Because lipases retain activity and selectivity in non-conventional media such as organic liquids, their use as biocatalysts in enantioselective synthetic reactions has considerably increased. 

The displacement of a tosylatc group in optically active compounds has given access to the preparation of ( —)-/ -2-fluorooctane (4) from ( + )-5 -2-oetyltosylate (3). The SN2 nucleophilic displacement with inversion has been conveniently earried out by using potassium fluoride in triethylene glycol.143 The product is formed in 100% optieal purity, but is contaminated with a mixture of octenes which can easily be removed. 

Since Dickinson s first determinations, crystal structures of many other complexes of various coordination numbers have been determined. All these investigations and others have provided a complete and direct confirmation of Werner s views to support his indirect configurational proofs obtained during the previous decades by preparation of isomers and resolution of optically active compounds (see Section 1.1.4), and today the terminology and concepts of coordination theory are routinely used in crystallography. 

The qualitative correlations between the absolute structure of the optically active compound used in the preparation of the catalytic complexes and the prevailingly absolute structure of the asymmetric carbon atoms in the main chain are reported in Table 2. 

This is the most widely used method for preparing optically active polymers in fact the polymerization of many optically active compounds having a vinyl or vinylidene double bond has already been described. 

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