Geometric isomers Stereoisomers

Since all the physical properties of two given enantiomers are the same in the absence of a chiral, or optically active, medium, their chromatographic resolution needs a different approach from the relatively simple separation of geometrical isomers, stereoisomers or positional isomers. Two methods are used. The older technique of indirect resolution, requires conversion of the enantiomers to diastereoisomers using a suitable chiral reagent, followed by separation of the diastereoisomers on a non-chiral GC or LC stationary phase. This technique has now been largely superseded by direct resolution, using either a chiral mobile phase (in LC) or a chiral stationary phase. A variety of types of chiral stationary phase have been developed for use in GC, LC and SFC(21 23). 

Two molecules with the same molecular formula and the same bond-to-bond connectivity that are not the same compound are called stereoisomers. Unless they are geometric isomers, stereoisomers must each contain at least one chiral center in the same location. There are two types of stereoisomers enantiomers and diastereomers. 

The CIS and trans forms of 1 2 dimethylcyclopropane are stereoisomers Stereoisomers are isomers that have their atoms bonded m the same order—that is they have the same constitution but they differ m the arrangement of atoms m space Stereoiso mers of the cis-trans type are sometimes referred to as geometric isomers You learned m Section 2 18 that constitutional isomers could differ m stability What about stereoisomers We can measure the energy difference between as and trans 1 2 dimethylcyclo propane by comparing their heats of combustion As illustrated m Figure 3 20 the two compounds are isomers and so the difference m their heats of combustion is a direct measure of the difference m their energies Because the heat of combustion of trans 1 2 dimethylcyclopropane is 5 kJ/mol (12 kcal/mol) less than that of its cis stereoisomer it follows that trans 1 2 dimethylcyclopropane is 5 kJ/mol (12 kcal/mol) more stable than as 1 2 dimethylcyclopropane... 

When additional substituents ate bonded to other ahcycHc carbons, geometric isomers result. Table 2 fists primary (1°), secondary (2°), and tertiary (3°) amine derivatives of cyclohexane and includes CAS Registry Numbers for cis and trans isomers of the 2-, 3-, and 4-methylcyclohexylamines in addition to identification of the isomer mixtures usually sold commercially. For the 1,2- and 1,3-isomers, the racemic mixture of optical isomers is specified ultimate identification by CAS Registry Number is fisted for the (+) and (—) enantiomers of /n t-2-methylcyclohexylamine. The 1,4-isomer has a plane of symmetry and hence no chiral centers and no stereoisomers. The methylcyclohexylamine geometric isomers have different physical properties and are interconvertible by dehydrogenation—hydrogenation through the imine. 

The cis and trans forms of 1,2-dimethylcyclopropane are stereoisomers. Stereoisomers are isomers that have then- atoms bonded in the sane order—that is, they have the sane constitution, but they differ in the anangernent of atoms in space. Stereoisomers of the cis-trans type are sometimes refened to as geometric isomers. You learned in Section 2.18 that constitutional isomers could differ in stability. What about stereoisomers ... 

A good example of applying the hydrazone method is the preparation of the optically active pheromone 34 (Scheme 2-22).38 Further study of the crude product prepared from SAMP-hydrazone and 3-pentanone 33 shows that, among the four possible stereoisomers, (Z,S, S )-isomer 35 predominates along with the minor (E,S,S)-isomer, the geometric isomer of 35. The final product 34 was obtained with over 97% enantiomeric excess (ee). 

Diastereoisomers are stereoisomers which do NOT have a mirror image of one another. Figure 11.20 shows the diastereoisomers of 2-butene (alkenes such as this are sometimes called geometric isomers and are a consequence of the prohibition of rotation about double bonds). If a vertical mirror was placed between the two structures in Fig. 11.20 they would not reflect onto one another. If the functionality is on the same side then the isomer is the cis-form, if on the opposite side then it is the trans- form. The chemical properties are very similar because the functional groups are identical. However, as they have different shapes their physical properties are different. Interconversion requires breaking and remaking bonds so these isomers are also stable under normal conditions. 

It is to be noted that geometrical isomers are now also classified as diastereoisomers. Therefore diastereomers are any stereoisomers which are not enantiomers of each other and the term is not restricted to optical isomers only. 

On the other hand, selective, usually applied to a synthesis, means that of all the possible isomers only one isomer is obtained. However, if the reaction product was/is a mixture of isomers one could speak then of the "degree of selectivity". Since usually one of the isomers will be the predominant isomer, we may say that the reaction (or the synthesis) is selective with respect to this particular isomer. As in the case of "specificity", we may refer to "regioselectivity" or to "stereoselectivity" (either diastereoselectivity or enantioselectivity) and may say, for instance, that a synthesis is 80% diastereoselective. According to the most updated terminology "diastereomers" are all the "stereoisomers" that are not "enantiomers", so geometrical isomers are also included in such a definition. 

To see why this is important, consider a butene (2-butene) in which the double bond is between the two central carbon atoms CH3—CH—CH—CH3. If we think about it for a bit, we can recognize that there are really two of these structures they are stereoisomers that are not enantiomers and not constitutional isomers. Such stereoisomers are termed diastereomers. Diastereomers in this class are also known by the older and largely obsolete term geometrical isomers. They differ in the way that the two methyl groups at the ends of the molecule are disposed with respect to each other. The two possibilities are ... 

We should compare this system with a 1,4-disubstituted cyclohexane such as 4-methylcyclo-hexanecarboxylic acid (see Section 3.4.4). There is a plane of symmetry in this molecule, so there are no chiral centres but geometric isomers exist, allowing cis and trans stereoisomers. The restrictions imposed by bridging have now destroyed any possibility of geometric isomerism. 

By definition, it is necessary to recognize geometric isomers, isotopomers and stereoisomers as distinct species. Moreover, there is the pragmatic issue that regio-selectivity, isotopic labeling and stereo-chemical investigations are three very important avenues of mechanistic enquiry. 

Diasteroisomers, also known as geometric isomers, have different relative orientations of their metal-ligand bonds. Enantiomers are stereoisomers whose molecules are nonsuperposable mirror images of each other. Enantiomers have identical chemical and physical properties except for their ability to rotate the plane of polarized light by equal amounts but in opposite directions. A solution of equal parts of an optically active isomer and its enantiomer is known as a racemic solution and has a net rotation of zero. 

Hydrogenation of the double bond in dehydroamino acids prepared from unsaturated 5(4H)-oxazolones derived from unsymmetrical ketones gives rise to two stereogenic centers. As a consequence, four stereoisomers are possible. If the hydrogenation of each geometric isomer is performed separately, then the erythro and threo pair of enantiomers can be obtained independently. In this respect, the unsaturated oxazolones from 2-butanone have been prepared as a Z/E) mixture. The mixture was separated and each stereoisomer was independently converted to the erythro and threo pairs of enantiomers. ... 

There are two major types of stereoisomer conformational isomers and configurational isomers. Configurational isomers include optical isomers, geometrical isomers, enantiomers and diastereomers. 

As noted previously, the classification of stereoisomers preferred by contemporary organic chemists is the enantiomer-diastereomer dichotomy17 and this may be quite conveniently applied to coordination compounds. Thus, complexes (9a) and (9b) are enantiomers, but (9a) and (9c), and (9b) and (9c), are diastereomers. Older terminology might have led to the description of A and B as optical antipodes and to (A+B) and C as geometrical isomers. 

Arrangements 1 and 2 are clearly different forms of the same structural isomer and are called stereoisomers (Gr. stereo, solid or space). The relationship between 1 and 2 may be expressed in terms of the geometry of the molecule and hence these forms have also been called geometrical isomers. (Recalling the provisos set down for this system—planarity and angles—the difference between 1 and 2 is merely the location of one A with respect to the other in the unit.)... 

In many of the above examples, especially those resulting in the formation of macrocyclic complexes, the metal-free macrocycles can be obtained as hydroperchlorate salts by combination of the amino and carbonyl fragments in the presence of perchloric acid. Such a procedure has resulted in the formation of an even wider range of macrocyclic complexes than is available by metal template methods. The two approaches are complementary, as different geometrical isomers and stereoisomers can be formed by the different methods in some cases. 

Stereoisomers that are not mirror images of each other are called dia-stereomers. Thus geometrical isomers (e.g., 5 and 6) are diastereomers, as are molecules that have two or more chiral centers but that are not enantiomers. For example, 7 and 8 are diastereomers of one another. 

Palladium-catalyzed reaction of bromo dienes 39 was complete after a few hours, and afforded spirocycles 40a and 40b as single regio- and stereoisomers (Scheme 12). The Heck spirocyclization reaction is regioselective, giving five-membered heterocycles. In addition, it is stereoselective because the Heck adducts were obtained as single geometric isomers [60]. 

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