Diastereomers and cis/trans isomers

R Stereoisomers (Section 4.2) are compounds whose atoms are connected in the same order but with a different geometry. Among the kinds of stereoisomers we ve seen are enantiomers, diastereomers, and cis-trans isomers (both in alkenes and in cycloalkanes). Actually, cis-trans isomers are just another kind of diastereomers because they are non-mirror-image stereoisomers. 

The submitters report obtaining 1.29 (12%) of the c/.v-diastereoisomer and 8.39 g (80%) of the trans-diastereoisomer. The submitters recommend that the purified diastereomers be stored in the freezer (-18°C). Both pure isomers slowly equilibrate to a 21 79 mixture of cis/trans isomers upon standing at ambient temperature for several weeks. 

A similar reaction of A-toluenesulfonyl derivatives of (.S )-alanine, phenylalanine, and valine (188-190) with PhPCl2 gave 4-methyl, benzyl, and isopropyl derivatives of 2-phenyl-1-p-toluenesulfonyl-l, 3,2-oxazaphospholidin-5-one, 191-193 in high yields (Scheme 53) [84], The ratios of the (2.V,4.V)/(2/f,4.V) diastereomers (which were designated as cis/trans isomers) were 1 1, 2 1, and 10 1 for 191a,b, 192a,b, and... 

Geomelric (cis-trans) isomers are stereoisomers because they differ only in the spatial arrangement of the groups. They are diastereomers and have different physical properties (m.p., b.p., etc.). 

Sertraline is the active pharmaceutical ingredient (API) in Pfizer s antidepressant Zoloft [25]. The developed commercial process employs an SMB chromatographic resolution of tetralone (Scheme 13.10) in >99% ee followed by diastereoselective reductive amination to give 95% sertraline (cis-isomer) and 5% trans-isomer the (4R)-tetralone can be racemized with an alkoxide base [8]. Asymmetric processes to sertraline have been described [26]. Our studies started with the original patented process involving palladium-catalyzed reductive amination of a tetralone to give a mixture of 80% racemic-cis and 20% racemic-trans diastereomers [27]. The cis-diastereomer can be purified by selective crystallization from toluene followed by diastereomeric crystallization of the (lS,4S)-enantiomer using (R)-... 

Although the term prochirality is frequently used, especially by biochemists, it suffers from a limitation which arises from a corresponding limitation in the definition of chirality. Molecules may display purely stereochemical differences without being chiral cis-tram isomers of olefins and certain achiral cis-trans isomers of cyclanes are examples. Thus (Fig. 2) (Z)- and ( )-1,2-dichloroethylene (4, 5) are achiral diastereomers, as are cis- and /rtww-1,3-dibromocyclobutanes (6, 7) being devoid of chirality these compounds have no chiral centers (or other chiral elements). Thus it is inappropriate to associate stereoisomerism with the occurrence of chiral... 

A stereocenter is an atom at which the interchange of two groups gives a stereoisomer. Stereocenters include both chirality centers and double-bonded carbons giving rise to cis-trans isomers. For example, the isomers of but-2-ene are achiral and they contain stereocenters (circled), so they would meet this definition. They have no chiral diastereomers, however, so they are not correctly called meso. 

The heating of petroleum products in the presence of a catalyst (usually an aluminosilicate mineral), causing bond cleavage to form alkenes and alkanes of lower molecular weight, (p. 315) (geometric isomers) Isomers that differ in their cis-trans arrangement on a ring or double bond. Cis-trans isomers are a subclass of diastereomers. (p. 291)... 

Due to the high aetivation barrier for cisitrans isomerization reactions at carbon-carbon double bonds ca. 260-270 kJ/mol [82]), it is often impossible to measure directly the non-catalyzed thermal equilibration reaction in solution. For 1,2-dichloroethene, however, the relative stability of its cis and trans isomers in various solvents has been determined by means of calorimetric measurements of heats of solution [202]. Surprisingly, these measurements show a quite similar solvent effect on both diastereomers, even though the cis isomer is a dipolar molecule and the trans isomer is not. Therefore, the position of this cisjtrans equilibrium should not be very solvent-dependent. 

Separations involving cis/trans isomers can also be accomplished by employing NPC. An example of this application is the separation of tricyclic antidepressant doxepin, which is marketed as a mixture of geometric isomers in a cis/trans ratio of 15 85 [41], When a spherisorb silica column is used with a hexane-methanol-nonylamine mobile-phase system, the cis isomer of doxepin elutes first. The structures of the two isomers and the chromatographic separation are shown in Figure 5-7. NPC has also been successfully employed in the separation of cis/trans isomers of steroids. Four diastereomers... 

The cycloaddition of 4-phenyl-3//-l,2.4-triazole-3,5(4//)-dione to ( , )- and ( ,Z)-2,4-hexadicne affords the expected cis- and rran.v-adducts 5, with >95 5% diastereoselectivity (capillary GC analysis). On the other hand, the cycloaddition of the (Z.Z)-diene affords both diastereomers, the wrong trans-isomer predominates22. The transids ratio principally depends on the temperature and, to a lesser degree, on the solvent. By following the reaction of the (Z.Z)-diene by 2H NMR (CDC13) at —55 C, it appears that the m-isomer is produced by rearrangement of the initially formed d.v-diazetidine. With methanol as the solvent, solvent adducts are produced from the (Z.Z)-diene, and in part from the (i. Z)-diene (see Section 7.2.10.1.). 

Since they are diastereomers, cis-trans isomers always differ in properties the differences may range from very slight to considerable. The properties of maleic acid are so different from those of fumaric acid (Table 4.2) that it is not surprising that they have different names. Since they generally have more symmetry than cis isomers, trans isomers in most cases have higher melting points and lower... 

Cyclic compounds can exhibit enantiomerism as well as geometric isomerism. A cyclic compound with two dissimilar chiral carbon atoms has two possible enantiomeric pairs. The cis isomer can exist as a pair of enantiomers and the trans isomer does the same. The two cis enantiomers are diastereomers of the two trans enantiomers. A cyclic compound with two similar chiral carbon atoms has a meso compound, the cis geometric isomer, and a pair of enantiomers, the trans geometric isomer. Again, the cis and trans isomers are related as diastereomers. 

The four stereoisomers of 3-chloro-2-butanol consist of two pairs of enantiomers. Stereoisomers 1 and 2 are nonsuperimposable mirror images. They, therefore, are enantiomers. Stereoisomers 3 and 4 are also enantiomers. Stereoisomers 1 and 3 are not identical, and they are not mirror images. Such stereoisomers are called diastere-omers. Diastereomers are stereoisomers that are not enantiomers. Numbers 1 and 4,2 and 3, and 2 and 4 are also diastereomers. (Cis-trans isomers are also considered to be diastereomers because they are stereoisomers that are not enantiomers.)... 

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