Stereochemistry anti elimination

Elucidating the stereochemistry of reaction at prochirality centers is a powerful method for studying detailed mechanisms in biochemical reactions. As just one example, the conversion of citrate to (ds)-aconitate in the citric acid cycle has been shown to occur with loss of a pro-R hydrogen, implying that the reaction takes place by an anti elimination mechanism. That is, the OH and H groups leave from opposite sides of the molecule. 

Anti stereochemistry (Section 7.2) The opposite of syn. An anti addition reaction is one in which the two ends of the double bond are attacked from different sides. An anti elimination reaction is one in which the two groups leave from opposite sides of the molecule. 

The conversion of long-chain alkanoate CoA esters into the alkenoate CoA esters by acyl-CoA oxidase involves an anti elimination reaction. The stereochemistry of the reaction in Candida lipolytica was established using stearoyl-CoA-labeled with H at the 2 R)-, 3(R)-, and 3(5)-positions (Kawaguchi et al. 1980). 

The nucleophilic attack on an acceptor-substituted allene can also take place at the acceptor itself, especially in the case of carbonyl groups of aldehydes, ketones or esters. Allenic esters are reduced to the corresponding primary alcohols by means of diisobutylaluminum hydride [18] and the synthesis of a vinylallene (allenene) by Peterson olefination of an allenyl ketone has also been reported [172]. The nucleophilic attack of allenylboranes 189 on butadienals 188 was investigated intensively by Wang and co-workers (Scheme 7.31) [184, 203, 248, 249]. The stereochemistry of the obtained secondary alcohol 190 depends on the substitution pattern. Fortunately, the synthesis of the desired Z-configured hepta-l,2,4-trien-6-ynes 191 is possible both by syn-elimination with the help of potassium hydride and by anti-elimination induced by sulfuric acid. Analogous allylboranes instead of the allenes 189 can be reacted also with the aldehydes 188 [250]. 

Stereochemistry Nonstereospecific anti Elimination (syn when anti impossible)... 

Notice the stereochemistry of Eq. 13-18, step a. Orbital interaction rules predict that if the elimination is a concerted process it should be syn. The observed anti elimination suggests a more complex mechanism involving participation of a nucleophilic group of the enzyme.97... 

The stereochemistry of /1-elimination reactions catalysed by D-galactonate dehydratase (GalD) and D-glucarate dehydratase (GlucD) enzymes is apparently not dictated by the pKas of the 7-protons of the carboxylate anion substrates.74 It had been observed previously that enzyme-catalysed dehydration initiated by abstraction of the a-proton (P a > 29) from a carboxylate anion substrate usually proceeds via anti elimination, whereas syn elimination occurs when the proton is a- to an aldehyde, ketone, or thioester and correspondingly more acidic (pKa < 25). 

It is not always easy to distinguish an elimination reaction that is following the Elcb mechanism from one that follows the E2 pathway because the Elcb reaction usually exhibits second-order kinetics also. However, because the Elcb reaction is not concerted, there are no strict requirements concerning the stereochemistry of the reaction. In contrast to the preferred anti elimination that occurs in the E2 mechanism, Elcb reactions often produce a mixture of stereoisomers, as illustrated in the following equation ... 

For eliminations, form the carbon-carbon double bond according to Zaitsev s rule (except the Hofmann elimination) and use anti elimination to determine the stereochemistry of E2 reactions. 

Problem 8.18 Given that an E2 reaction proceeds with anti periplanar stereochemistry, draw the products of each elimination. The alkyl halides in (a) and (b) are diastereomers of each other. How are the products of these two reactions related ... 

The stereochemistry of the elimination of the p-hydroxysilane at silicon has been investigated. In studies by Larson and coworkers, the 3-hydroxyalkyl(l-iuq)hthyl)phenylmethylsilanes (307) and (309) were isolated and subjected to elimination conditions to ascertain the stereochemistry of the elimination on the silyl groip (Scheme 44). The acid-catalyzed eliminations proceed with inversion of stereochemistry at silicon, while the base-catalyzed elimination occurred with retention. These results are in agreement with the mechanism proposed of anti elimination under acidic conditions and syn elimination under basic. While the optically pure silicon was useful for determining the course of the elimination, it could not be utilized in asymmetric synthesis. Addition of the anion to various carbonyls afforded virtually no diastereoselectivity, and it was not possible to separate the diastereomers formed either by crystallization or by chromatography. 

Sicher, J., Svoboda, M., Pankova, M., Zavada, J. Stereochemistry. LXII. Hofmann-Saytzeff and the syn-anti elimination dichotomy. Relation between the two phenomena. Collect. Czech. Chem. Commun. 1971,36, 3633-3649. 

The key to this problem is to understand that Hofmann elimination occurs via an E2 mechanism requiring anti coplanar stereochemistry, whereas Cope elimination requires syn coplanar stereochemistry. 

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