Preparation of optically-active compounds

Many optically-active organic molecules are present in plants and animals, and they can often be isolated and obtained in a pure form. In recent years, considerable success has been achieved in the selective synthesis of individual isomers. However, laboratory preparations of compounds that can exhibit optical activity normally yield 50-50 (racemic) mixtures of the two optical isomers and hence produce an optically-inactive material (Section 3.4). Therefore, the basic step in the laboratory preparation of an optically-active coordination compound is separation from its optical isomer. For example, racemic [Co(en)3] is readily prepared by the air oxidation of a cobalt(II) salt 

The most common separation techniques involve the principle that each of a pair of optical isomers will interact differently with a third optically-active material. There is a subtle structural difference between optical isomers, and this will lead one isomer to be more strongly attracted to a third dissymmetric molecule. For example, the salt ( + )-[Co(en)3]((+)-tartrate)CF5Fl20 is less soluble than (-)-[Co(en)3](( + )-tartrate)CF5H20. This indicates that ( + )-[Co(en)3] forms a more stable crystalline lattice with a ( + )-tartrate than does ( — )-[Co(en)3]. Therefore, the addition of a solution containing ( + )-tartrate anion to a concentrated solution of racemic [Co(en)3] causes the precipitation of (+ )-[Co(en)3](( + )-tartrate)Cl 5FI2O. The (-)-[Co(en)3] remains in solution and can be collected by the addition of F, which forms ( —)-[Co(en)3]l3. This product will be contaminated with any (+ )-[Co(en)3] that was not removed in the tartrate precipitation. 

The preferential precipitation of one of a pair of optical isomers by another optically-active compound is the principal method for resolving pairs of optical isomers. The method can be used, however, only if the isomers to be separated can be obtained as charged ions, since their precipitation as salts is required. 

Write appropriate balanced equations and give approximate experimental conditions for the preparation of each of the following  

Complete and balance the following equations. Unless otherwise stated, the reactions proceed at room temperature in water solution. 

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

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... 

Asymmetric cyclization using chiral ligands offers powerful synthetic methods for the preparation of optically active compounds [39]. After early attempts [40,41], satisfactory optical yields have been obtained in a number of cases. Synthesis of the optically active cA-decalin system [42] was carried out with high enantioselectivity based on the differentiation of enantiotopic C=C double bonds [43]. The cyclization of the triflate 93 gave the cA-decalin 94 with 95% ee in 78% yield using (i )-BINAP. A mixture of 1,2-dichloroethane and f-BuOH is the best solvent, and the asymmetric synthesis of vemolepin (96) via Danishefsky s key intermediate 95 has been achieved [44]. 

In many respects, chiral compounds have been regarded as special entities within the tine chemical community. As we will see, the possession of chirality does not, in many respects, make the compound significantly more expensive to obtain. Methods for the preparation of optically active compounds have been known for more than 100 years (many based on biological processes). The basic chemistry to a substrate on which an asymmetric transformation is then performed can offer more challenges in terms of chemistry and cost optimization than the exalted asymmetric step. 

Fig. 31 Preparation of optically active compounds employing HLADH and NADH, which are codeposited onto glass beads in a monophasic organic solvent, (a) Reduction reaction to produce chiral alcohols in the presence of ethanol for NADH regeneration, (b) Oxidation reaction to produce enantiomerically pure alcohol or a ketone out of the racemic mixture coupled with the reduction of isobutyraldehyde to regenerate NAD+...

PLE has usually been applied to the enantioselective preparation of optically active compounds, but its use can be extended to chemo- or regioselective hydrolyses. A continuous process for the separation of a cis/trans unsaturated ester was realized using immobilized PLE (eq 8). ... 

Most frequently, cuprates or other C-nucleophiles are employed in homo-Michael additions which often serve as the basic reactions for constructing natural product skeletons The preparation of optically active compounds also profits from this type of... 

Although initially prepared and evaluated as a racemate, the NMDA antagonist activity was likely to reside primarily in a single enantiomer. The stereoselective nature of the NDMA receptor is well established, albeit not completely understood. Consequently, several attempts have been undertaken to develop synthetic protocols that would allow preparation of optically active compounds. Early reports of preparation of optically active co-amino-o-carboxyalkylphosphonic acids describe the preparation of (.S )-A P-3 from an optically active amino nitrile prepared by reaction of diethyl 1-formylphosphonate with hydrogen cyanide and (5)-(-)-a-methylbenzylamine. Acid hydrolysis, enrichment of the diastereomers by fractional recrystaUization, and debenzylation lead to the isolation of (.S )-A P-3 in 86% enantiomeric excess. " Recently reported procedures, which use chemoenzymatic processes, offer a more convenient and mild approach for the production of optically pure aminophosphonic acids. Enzymatic hydrolysis of amides using penicillinacylase (EC... 

In this section, one-pot preparations of optically active compounds by a combination of solid-state reaction and enantioselective inclusion complexation in a water suspension medium are described. In order to establish the suspension procedure as a general enantiomeric separation method, enantiomeric separations of various compounds by complexation in hexane and water suspension media were studied. Furthermore, by combining enantioselective inclusion complexation with a chiral host in the solid state with distillation, a fascinating enantiomeric separation method by fractional distillation was established. 

Ito, K., Harada, T., Tai, A., and Izumi, Y. (1979) A facile method for the preparation of optically pure 2,4-pentanediol. An application of as3mimetrically modified nickel catalyst for the preparation of optically active compounds, Chem. Lett. 1049 - 1050. 

A strange method of preparation of optically active compounds without any chiral inductors was described using an electrochemical cell with electrodes of special asymmetric configuration made of barium titanate Reduction of fumaric acid resulted in (R)-(+)-malic acid with an ee of 17%, or... 

Methods for the preparation of optically active compounds have been reviewed. Still and his co-workers recently developed the hydroboration of acyclic 1,4-dienes as a method for the controlled creation of stereocentres. Two groups have now exploited this method in a short synthesis of the Prelog-Djerassi lactone (111). The key step in both routes is the hydroboration-oxidation of (109) to (110) that is highly stereoselective with respect to three of the four stereocentres of (110). 

SOMO Activation Within the field of aminocatalysis, asymmetric organo-SOMO (singly occupied molecular orbital) catalysis has recently emerged as a powerful technique for the preparation of optically active compounds. In this context, MacMillan and coworkers described in 2008 the formation of y-oxyaldehydes from aldehydes and styrenes by organo-SOMO catalysis [25]. The condensation between the amine catalyst 46 and an aldehyde gave rise to an enamine intermediate, which was then oxidized by ceric ammonium nitrate (CAN) to give a radical cation. Reaction of this radical cation with a nonactivated olefin, namely styrene, led to the... 

Perhaps one of the most challenging aspects of complex molecule synthesis is control of the absolute sense of stereochemistry for the preparation of optically-active compounds. In 1989, Shibasaki and Overman independently reported the first examples of asymmetric Heck reactions. These efforts focused on intramolecular cyclization reactions, which display extra elements of regiocontrol. To date, the asymmetric intramolecular Heck has been exploited in the synthesis of terpenoids, akaloids and polyketides, forging key tertiary and quaternary stereocentres. ... 

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