Chiral molecules reactions producing enantiomers

Inoue s work (35), as well as that of others (36) discussed below, points to an important feature in the study of asymmetric catalysis. Once it has been shown that a reaction can be catalyzed by a chiral molecule to produce one enantiomer in excess, practically useful optical yields can usually be achieved given sufficient... 

We consider a production of chiral enantiomers R and S from an achiral substrate A in a closed system. Actually, in the Soai reaction, chiral molecules are produced by the reaction of two achiral reactants A and B as A + R or A + B -> S. But in a closed system a substrate of smaller amount controls... 

A reaction that produces a predominance of one enantiomer over other is known as enantioselective synthesis. To carry out an enantioselective reaction, a chiral reagent, solvent, or catalyst must assert an influence on the course of the reaction. In nature, most of the organic or bioorganic reactions are enantioselective, and the chiral influence generally comes from various enzymes. Enzymes are chiral molecules, and they possess an active site where the reactant molecules are bound momentarily during the... 

Aldehydes, ketones, and quinones react with ketenes to give p-lactones, diphenylketene being used most often. The reaction is catalyzed by Lewis acids, and without them most ketenes do not give adducts because the adducts decompose at the high temperatures necessary when no catalyst is used. When ketene was added to chloral Cl3CCHO in the presence of the chiral catalyst (+ )-quinidine, one enantiomer of the p-lactone was produced in 98% enantiomeric excess.777 Other di- and trihalo aldehydes and ketones also give the reaction enantioselectively, with somewhat lower ee values.778 Ketene adds to another molecule of itself ... 

This obviously is unlikely for the given example because there is no reason for cyanide ion to have anything other than an exactly equal chance of attacking above or below the plane of the ethanal molecule, producing equal numbers of molecules of the enantiomers, 21 and 22. However, when a chiral center is created through reaction with a dissymmetric (chiral) reagent, we should not expect an exactly 1 1 mixture of the two possible isomers. For example, in an aldol-type addition (Section 18-8E) of a chiral ester to a pro-chiral ketone the two configurations at the new chiral center in the products 23 and 24 are not equally favored. That is to say, asymmetric synthesis is achieved by the influence of one chiral center (R ) on the development of the second ... 

Small fluctuations in the ratio of the two enantiomers are considered to be present in racemic mixtures of chiral molecules [14,101]. We thought that, when a reaction system involves asymmetric autocatalysis with amplification of ee, the initial small fluctuation of ee in racemic mixtures that arises from the reaction of achiral reactants can produce an enantiomerically enriched product. We anticipated that when z-P Zn was treated with pyrimidine-5-carbaldehydes without adding any chiral substance, extremely slight enan-tioenrichment would be induced statistically in the initially formed zinc alkoxide of the alkanol, and that the subsequent amplification of chirality by asymmetric autocatalysis would produce the pyrimidyl alkanol with detectable enantioenrichment (Scheme 19). 

Photochemical reactions—asymmetric as well as nonasymmetric ones—take their outset from electronically excited states of the reactant. In this chapter, direct cpl excitation is covered, sensitized reactions are discussed in Chap. 4. Asymmetric photochemistry produces new chirality in a reaction system. The cpl-induced reactions are often called absolute asymmetric, as there is no net chirality in the reactants. This discriminates asymmetric photochemistry from the photochemistry of chiral molecules, which can be induced by nonpolarized light. The newly created chirality in cpl-induced reactions becomes apparent in an excess of the amount of one reactant or product enantiomer over the other. This enantiomeric excess (ee) in a mixture of R and S enantiomers is defined as... 

Despite its importance, the ability to obtain chiral molecules in enantiopure form is a difficult challenge. One strategy to make a pure enantiomer is to produce the racemic mixture and then separate both enantiomers and effectively throw away the undesired enantiomer. Separation of enantiomers is a very difficult endeavour, and destroying half the reaction product at every stereogenic step is not viable as yields in multi-step synthesis decrease exponentially. 

Most of the biochemical reactions that take place in the body and many organic reactions in the laboratory yield products with chirality centers. For example, addition of HBr to 1-butene yields 2-bromobutane, a chiral molecule. What predictions can we make about the stereochemistry of this chiral product If a single enantiomer is formed, is it R or S If a mixture of enantiomers is formed, how much of each In fact, the 2-bromobutane produced is a racemic mixture of R and S enantiomers. Let s see why. 

The Diels-Alder reaction has high stereoselectivity. One way to create enantiomeri-cally pure target molecules is to use a chiral auxiliary, which is a chiral molecule available as a single enantiomer that is bonded to the starting material. The use of a chiral auxiliaiy can influence the resulting stereochemistry of a Diels-Alder reaction, producing a desired enantiomer in excess. The chiral auxiliary is then removed. 

We have just looked at the different interactions between a single enantiomer of a chiral molecule and an enantiomeric pair of molecules (Fig. 4.26). Let s take this interaction business to its limit and see what happens if we actually form bonds to produce new molecules. We can t worry yet about real chemical reactions—we are still in the tool-building stages—but that doesn t matter. We can imagine some process that replaces the two X substituents in Figure 4.31 with a chemical bond, shown in aU succeeding figures with a blue screen. ... 

A reaction that in an achiral solvent would produce a racemic product, when carried out in a chiral solvent may result in the predominance of one of the enantiomers. This may result either from differential solvation of the reactants or of the transition state. Bosnich (1967) has shown that a symmetric solute in a chiral solvent may exhibit induced asymmetry, which can influence the ratio of enantiomers formed. Where the effect is through the transition state, one would expect the effect to be greatest if the solvent were involved directly, especially (in view of the foregoing) if two or more H-bonds are involved. If A and B are non-chiral molecules, but their adduct AB exists as enantiomers AB+ and AB-, the activated complexes in the reactions ... 

Reaction of an achiral reagent with a molecule exhibiting enantiotopic faces will produce equal quantities of enantiomers, and a racemic mixture will result. The achiral reagent sodium borodeuteride, for example, will produce racemic l-deM/eno-ethanol. Chiral reagent can discriminate between the prochiral faces, and the reaction will be enantioselective. Enzymatic reduction of acetaldehyde- -[Pg.106]

Figure 10.10 The synthesis of 2R-methylbutanoic acid, illustrating the use of a chiral auxiliary. The chiral auxiliary is 2S-hydroxymethyltetrahydropyrrole, which is readily prepared from the naturally occurring amino acid proline. The chiral auxiliary is reacted with propanoic acid anhydride to form the corresponding amide. Treatment of the amide with lithium diisopropyla-mide (LDA) forms the corresponding enolate (I). The reaction almost exclusively forms the Z-isomer of the enolate, in which the OLi units are well separated and possibly have the configuration shown. The approach of the ethyl iodide is sterically hindered from the top (by the OLi units or Hs) and so alkylation from the lower side of the molecule is preferred. Electrophilic addition to the appropriate enolate is a widely used method for producing the enantiomers of a-alkyl substituted carboxylic acids...

Among the many reactions of these species is the conversion to chiral species such as 18-D-XIX. This compound can be obtained in enantiomerically pure form and can be converted to the CpRe(NO)PPh3 ion.69 This ion is a chiral Lewis base that binds a variety of prochiral molecules (olefins, ketones, aldehydes, amines). With these adducts one may conduct numerous reactions where enantiomeric excesses >98% are obtained. As an example, a prochiral methyl ketone will bind selectively, as in 18-D-XX and is then subject to attack by R X to produce only one enantiomer of the RR MeCO product. 

One of the outstanding characteristics of enzymes is that they are able to function as enantioselective catalysts and carry out chemical reactions with absolute stereospecificity. As a result, most natural compounds are produced as optically pure enantiomers. The enantioselectivity of enzymatic catalysis is ascribed to the formation of a multibonded complex of substrate and reagent within the active center of the chiral enzyme molecule. The creation of chemical systems capable of serving as enantioselective catalysts represents one of the central and most challenging problems of modern chemistry. In the last decades. 

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