Double-bond diastereomers

Another type of isomerism is geometric isomerism. While C—C bonds rotate freely, the rotation of C=C bonds requires a larger amount of energy, therefore such a rotation seldom happens at room temperature. This inability of a double bond to rotate is known as hindered rotation, resulting in the formation of the cis (Z) isomer and the trans (E) isomer. Such pairs of geometric isomers are sometimes called double-bond diastereomers. 

The double bond m 2 methyl(methylene)cyclohexane is prochiral The two faces however are not enantiotopic as they were for the alkenes we discussed m Section 7 9 In those earlier examples when addition to the double bond created a new chirality cen ter attack at one face gave one enantiomer attack at the other gave the other enantiomer In the case of 2 methyl(methylene)cyclohexane which already has one chirality center attack at opposite faces of the double bond gives two products that are diastereomers of each other Prochiral faces of this type are called diastereotopic... 

The enantiomers are obtained as a racemic mixture if no asymmetric induction becomes effective. The ratio of diastereomers depends on structural features of the reactants as well as the reaction conditions as outlined in the following. By using properly substituted preformed enolates, the diastereoselectivity of the aldol reaction can be controlled. Such enolates can show E-ot Z-configuration at the carbon-carbon double bond. With Z-enolates 9, the syn products are formed preferentially, while fi-enolates 12 lead mainly to anti products. This stereochemical outcome can be rationalized to arise from the more favored transition state 10 and 13 respectively ... 

Cis-trans diastereomers (substituents on same side or opposite side of double bond or ring)... 

In the third sequence, the diastereomer with a /i-epoxide at the C2-C3 site was targeted (compound 1, Scheme 6). As we have seen, intermediate 11 is not a viable starting substrate to achieve this objective because it rests comfortably in a conformation that enforces a peripheral attack by an oxidant to give the undesired C2-C3 epoxide (Scheme 4). If, on the other hand, the exocyclic methylene at C-5 was to be introduced before the oxidation reaction, then given the known preference for an s-trans diene conformation, conformer 18a (Scheme 6) would be more populated at equilibrium. The A2 3 olefin diastereoface that is interior and hindered in the context of 18b is exterior and accessible in 18a. Subjection of intermediate 11 to the established three-step olefination sequence gives intermediate 18 in 54% overall yield. On the basis of the rationale put forth above, 18 should exist mainly in conformation 18a. Selective epoxidation of the C2-C3 enone double bond with potassium tm-butylperoxide furnishes a 4 1 mixture of diastereomeric epoxides favoring the desired isomer 19 19 arises from a peripheral attack on the enone double bond by er/-butylper-oxide, and it is easily purified by crystallization. A second peripheral attack on the ketone function of 19 by dimethylsulfonium methylide gives intermediate 20 exclusively, in a yield of 69%. 

The Diels-Alder adduct 8 formed in a mixture with 7 by treatment of porphyrin 6 with dimethyl acetylenedicarboxylate undergoes a base-induced migration of a C —C double bond yielding a single diastereomer 9 with the thermodynamically favored tram arrangement of the methyl group and the methoxycarbonyl substituent.201... 

The predominating onti-diastereomers of the primary adduct form an ( (-double bond on anti elimination and a (Z)-double bond on syn elimination, the latter proceeding frequently on warming of the reaction mixture to room temperature. 

The addition of enolate anions to (E)- and (Z)-3,3,3-trifluoro-l-[(4-methylphenyl)sulfinyl]-1 -propene has been investigated (E)- and (Z)-a,/(-unsaturated sulfoxides undergo addition in the opposite stereochemical sense3,4. In general, yields and product diastereoselection are high. When the -position of the double bond of the enolate is substituted then all four diastereomer-ic products result. 

Active Substrate. If a new stereogenic center is ereated in a molecule that is already optically active, the two diastereomers are not (except fortuitously) formed in equal amounts. The reason is that the direction of attack by the reagent is determined by the groups already there. For certain additions to the carbon-oxygen double bond of ketones containing an asymmetric a carbon. Cram s rule predicts which diastereomer will predominate (diastereo-selecti vity). ... 

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

Scheme 6.13 gives some examples of Cope and oxy-Cope rearrangements. Entry 1 shows a reaction that was done to compare the energy of chair and boat TSs. The chiral diastereomer shown can react through a chair TS and has a AG about 8 kcal/mol lower than the meso isomer, which must react through a boat TS. The equilibrium is biased toward product by the fact that the double bonds in the product are more highly substituted, and therefore more stable, than those in the reactant. 

Table 5 summarizes the reactions of isoprene with aromatic aldehydes and unsaturated aldehydes. Salicylaldehyde provides the expected product as a cyclic boric ester derivative and shows apparently lower stereoselectivity, giving a mixture of 1,3-anti and 1,3-syn isomers in a ratio of 6 1 (run 1, Table 5). 2-Furfural reacts as usual and provides a 1,3-anti isomer as a single diastereomer in good yield (run 2). Unsaturated aldehydes, irrespective of their substitution patterns, undergo homoallylation selectively with excellent 1,3-anti selectivity, the geometry of the double bond of the starting aldehydes remaining intact (runs 3-5). 1,2-Addition to unsaturated aldehyde takes place selectively and no 1,4-addition is observed.

On further exploration it could be shown that the desilylated precursors 1-90 (Scheme 1.24) permit formation of the aromatized products 1-91 and its double bond isomer in up to 90 % yield, starting from the E-compound as a mixture of two diastereomers with a (Z)-configuration of the double bond, 1-90 gave 50% yield of 1-91. 

It has been assumed that formation of the cis-fused product 2-771 in the domino reaction of aldehyde 2-769 is due to a strongly favored exo-Z-syn transition state 2-770. The endo-E-syn structure is prohibited by the rigidity of the acetonide existing in 2-769, whereas the proximity of the same moiety to the benzyloxymethyl substituent at the double bond disfavors the exo-E-anti transition state, which would be responsible for the formation of the trans-fused diastereomer. 

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