Diastereoisomerism

Diastereoisomerism is encountered in a number of cases such as achiral molecules without asymmetric atoms, chiral molecules with several centers of chirality, and achiral molecules with several centers of chirality (meso forms). Such cases can be encountered in acyclic and cyclic molecules alike, but for the sake of clarity these two classes of compounds will be considered separately. 

A molecular structure such as the one shown in diagram XLII is achiral (presence of a plane of symmetry), but when a b and c = d it can exist in two diastereoisomeric forms. When the two largest or remarkable substituents are on the same side of the double bond, the isomer is cis, and it is designated trans in the other case. Ambiguities have been encountered, and it is recommended to designate as (Z) the isomer with the two sequence rule-preferred substituents on the same side of the double bond (usually the cis-form), and as (E) the other isomer (usually the Wwts-form) (XLIII a H,c H) ([53], and refs, therein). 

7r-Diastereoisomerism is most frequently encountered with carbon-carbon double bonds (XLII, X = Z = C), but also with carbon-nitrogen and nitrogen-nitrogen double bonds. The term w-diastereoisomerism is more useful than the usual designations of cis-fra/w-isomerism or geometrical isomerism since it conveys the chemical origin and the correct description of the stereoisomerism. It also avoids any confusion with m-frans-isomerism in cyclic systems where no double bond is involved [54], 

Diastereoisomers have different relationships between nonbonded atoms, and as a consequence their energy content is different. It is generally found that due to steric effects the more extended (trans) isomer is more stable than the m-isomer by 1-10 kcal/mol. For example, (E)-2-butene (XLIV) is more stable than its (Z)-isomer by 1 kcal/mol [55]. However, through-bond and through-space attractive orbital interactions have been calculated in several cases to favor the c/s-isomer. Thus, (Z)-l-methoxypropene (XLV) is more stable than its (E)-diastereoisomer by about 0.5 kcal/mol [55]. 

In the case of the carbon-nitrogen double bond, the reaction of isomerization can occur via rotation about the double bond, and by nitrogen inversion (XLVII). The latter process as a rule is strongly favored over rotation, resulting in a lowered barrier of overall isomerization as compared to ethylenes. For many imines (XLVII, c = H), this barrier is in the range 20-30 kcal/mol. Electronegative substituents on the nitrogen atom increase stability toward inversion, as evidenced by the relative stability of oximes (XLVII, c = OH) and hydrazones (XLVII, c = NRR ) [56]. 

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When the intermediates were also substituted in the 5-position both possible diastereoisomeric forms were detected by NMR spectroscopy. 

Diastereoisomeric Salts. The formation of salts of optically active bases with racemic acids or of optically active acids with racemic bases leads to diastereomeric mixtures which may be resolved by the differential solubiUty of the components of such mixtures (49), ie,... 

For 1,3-dithiolanes the ring is flexible and only small energy differences are observed between the diastereoisomeric 2,4-dialkyl derivatives. The 1,3-oxathiolane ring is less mobile and pseudoaxial 2- or 5-alkyl groups possess conformational energy differences (cf. 113 114) see also the discussion of conformational behavior in Section 4.01.4.3. 

I) of which one form (picrate, m.p. 116°) is identical with dl-dihydro-de-N-methylheliotridane and the other (picrate, m.p. 126°) is diastereoisomeric with, and convertible into, it by, dehydrogenation to the corresponding pyrrole and hydrogenation of the latter in presence of copper chromite as catalyst. 

Br. CHa. CHa. CHa. CH(NHa). CH(CHa). CHa. CHjBr HBr. which on treatment with dilute alkali gives di-heliotridane (II). As the latter contains two asymmetric carbon atoms, two diastereoisomeric racemates might be produced in this reaction but only one was formed. It had density and refractive index in general agreement with those recorded for Z-heliotridane, as were also the melting points of characteristic derivatives. Density Df °0-902, refractive index wf, 1-4638 (<. with Adams and Rogers,3i Df ° 0-935, iijf° 1-4641), picrate, m.p. 234-6° (literature 232-6°), picrolonate, m.p. 162-3°, aurichloride, m.p. 200-1° (Konovalova and Orekhov give for these two constants 152-3° and 199-200° respectively). 

When the 1-monoximes or dioximes of 4-acetyl-l-tetralones are hydrogenated in the presence of palladium, mixtures of diastereoisomeric 1-aminotetralones are formed. The m-aminoketone isomers readily form dehydrobenzoisoquinuclideines (3,4-disubstituted-1,4-dihydro-1,4-ethano-isoquinolines). Quaternary immonium salts prepared from these bicyclic imines are then converted by bases to bicyclic enamines [2,4-disubstituted-3-alkylidene-1,4-ethano-1,2,3,4-tetrahydroisoquinolines (25)]. 

The [2 + 2] cycloaddition reaction of A -benzyl-l,4-dihydropyridine 34b with acrylonitrile, followed by catalytic reduction gave two pairs of diastereoisomeric amides 36 and 37 with a low diastereomeric excess, probably due to the large distance between the asymmetric center and the site of acrylonitrile attack. Compounds 36 and 37 were resolved into the four individual diastereoisomers (ca 5% for compound 36 and 15% for 37) [97JCR(M)321], Irradiation of 1,4-dibenzyl-1,4,5,6-tetrahydropyridine 38 in the presence of 29 gave two stereoisomers. 

Quinidine, a natural product epimeric with quinine at Cg and C9, was accessed through the diastereoisomeric trans epoxide prepared from 86 by SAD, in this case by using AD-mix a [2b, 41]. 

This area of reactivity has been the subject of excellent reviews (J5). Silyl enol ethers are not sufficiently nucleophilic to react spontaneously with carbonyl compounds they do so under the influence of either Lewis acids or fluoride ion, as detailed above. Few clear trends have emerged from the somewhat limited number of definitive studies reported so far, with ambiguities in diastereoisomeric assignments occasionally complicating the issue even further. 

Given a good diastereoisomeric excess in the initial formation of the /3-hydroxysilane, either geometrical isomer of the alkene can be obtained. 

These alkene isomers are separately available (4) by treatment of threo-S-trimethylsilyloctan-4-ol, prepared by reduction of the corresponding ketone with DIBAL in pentane at —120°C, with base or acid. The preparation of 5-trimethylsilyloctan-4-one itself illustrates three general procedures the addition of alkyl lithium reagents to vinylsilanes to generate a-lithiosilanes, the preparation of complex /5-hydroxysilanes, as diastereoisomeric mixtures, and the oxidation of such compounds to /8-ketosilanes... 

Chiral alcohols have also been used in an asymmetric synthesis of sulphoxides based on halogenation of sulphides. Johnson and coworkers have found319 that the reaction of benzyl p-tolyl sulphide with JV-chlorobenzotriazole (NCBT) followed by addition of (—) menthol and silver tetrafluoroborate afforded diastereoisomeric menthoxysulphonium salts 267 which, upon recrystallization and hydrolysis, gave benzyl p-tolyl sulphoxide with 87% optical purity (equation 145). More recently, Oae and coworkers reported320 that optically active diaryl sulphoxides (e.e. up to 20%) were formed either by hydrolysis or thermolysis of the corresponding diaryl menthoxysulphonium salts prepared in situ from diaryl sulphides using ( —) menthol and t-butyl hypochlorite. 

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