Anti-elimination reactions

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). 

Fig. 26 The elimination of HF from the 0-fluoroketone [68] is catalysed by antibody 1D4, elicited to hapten [70], to form the disfavoured (Z)-olefin [71]. This contrasts with the spontaneous process in which an anti-elimination reaction yields the ( )-<, 0-unsaturated ketone [69], The syn-eclipsed conformation of [70] is shaded.

The term stereoselective is often confused with the term stereospecific, and the literature abounds with views as to the most satisfactory definition. To offer some clarification, it is perhaps timely to recall a frequently used term, introduced a decade or so ago, namely the stereoelectronic requirements of a reaction. All concerted reactions (i.e. those taking place in a synchronised process of bond breaking and bond forming) are considered to have precise spatial requirements with regard to the orientation of the reactant and reagent. Common examples are SN2 displacement reactions (e.g. Section 5.10.4, p. 659), E2 anti) elimination reactions of alkyl halides (e.g. Section 5.2.1, p.488), syn (pyrolytic) elimination reactions (Section 5.2.1, p.489), trans and cis additions to alkenes (e.g. Section 5.4.5, p. 547), and many rearrangement reactions. In the case of chiral or geometric reactants, the stereoisomeric nature of the product is entirely dependent on the unique stereoelectronic requirement of the reaction such reactions are stereospecific. 

The solvent-influenced synjanti dichotomy for bimolecular eliminations of acyclic and medium-ring bromides, tosylates, and onium salts has been reviewed [395, 693] and will be mentioned only briefly. As a rule, the s jn-elimination pathway gains importance in non-dissociating solvents, while dissociating solvents facilitate the more common anti-elimination reaction. The more unusual s jn-elimination is favoured in non-dissociating solvents because of ion-pair association, which favours a cycHc six-membered activated eomplex as shown in Eq. (5-151a) see reference [395]. 

Dautzenberg and Knozinger also pointed out that adsorbed alcohol can exist in two conformations, with respect to the a-Me group and the variable )3-R group, namely antiperiplanar and synclinical. The former is thermodynamically more stable and would lead to rra s -2-olefin by anti-elimination. Reaction is nevertheless more probable for the synclinical conformation because the approach of jS-H to a basic site is less hindered for the latter. 

Tetraorganostannanes o of the type of bis-[2-(acyloxy)alkyl]diorganostannanes, are non-catalytic tin compounds, which can be heat-activated by anti -elimination reaction leading to catalytically active bis(acyloxy)dialkylstannanes.4i... 

The retrosynthetic transform for syn elimination is that shown for the anti elimination reactions except that the less substituted alkene is the target ... 

Entry 5 is an example of a stereospecific anti elimination reaction of an alkyl halide in which the transition state requires the proton being removed and the bromide lost to be in an anti orientation with respect to each other. The dias-tereomeric threo- and eryfhro-l,2-diphenyl-l-bromopropanes undergo base-catalyzed jS-elimination to produce stereoisomeric products. Entry 6 is an example of pyrolytic elimination requiring a syn orientation of the proton being removed and the amine oxide nitrogen atom. This elimination reaction is a concerted one in which the proton is abstracted by the oxygen of the amine oxide group. 

The enolase superfamily is now composed of at least 23 distinct proteins " of which functions have been experimentally verified for 11. The overall reactions catalyzed by the superfamily members of known function include racemization, epimerization, and both syn and anti elimination reactions involving substantially different substrates. While all of the substrates used by these enzymes contain a proton or to a car-boxylate group, none of the superfamily members is known to cross-react with the substrate of another family member. 

The first example of a stereo electronic effect in this text concerned anti elimination in E2 reactions of alkyl halides (Section 5 16)... 

The stereochemistry of the most fundamental reaction types such as addition, substitution, and elimination are described by terms which specify the stereochemical relationship between the reactants and products. Addition and elimination reactions are classified as syn or anti, depending on whether the covalent bonds which are made or broken are on the same face or opposite faces of the plane of the double bond. 

We have previously seen (Scheme 2.9, enby 6), that the dehydrohalogenation of alkyl halides is a stereospecific reaction involving an anti orientation of the proton and the halide leaving group in the transition state. The elimination reaction is also moderately stereoselective (Scheme 2.10, enby 1) in the sense that the more stable of the two alkene isomers is formed preferentially. Both isomers are formed by anti elimination processes, but these processes involve stereochemically distinct hydrogens. Base-catalyzed elimination of 2-iodobutane affords three times as much -2-butene as Z-2-butene. 

These reactions proceed by alkoxide or fluoride attack at silicon which results in C—Si bond cleavage and elimination of the leaving group from the fi carbon. These reactions are stereospecific anti eliminations. 

Stereospecific reaction (Section 7.13) Reaction in which stereoisomeric starting materials give stereoisomeric products. Terms such as syn addition, anti elimination, and inversion of eonfiguration describe stereospecific reactions. 

Progressive departure from the fundamental structure of the lead agent cimetidine led to the anti ulcer agent oxmetidine (47). The synthesis involves -methylation (CH3I) of the 2-thiouracil intermediate and is followed by an addition-elimination reaction with 2-(5-methyl-4-imidazolylmethylthio) ethylamine to give oxmetidine (47). ... 

Another entry into the anti ulcer sweepstakes is etinfidine (50). It is synthesized by displacement of halide from 4-chloromethyl-5-methylimidazole (4 ) with substituted thiol The latter is itself made from thiourea analogue by an addition-elimination reaction with cysteamine 52. °... 

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. 

CHAPTER 11 Reactions of Alkyl Halides Nucleophilic Substitutions anti Eliminations... 

Figure 11.22 Elimination reactions of menthyl chloride. E2 conditions (strong base in 100% ethanol) lead to 2-menthene through an anti periplanar elimination, whereas El conditions (dilute base in 80% aqueous ethanol) lead to a mixture of 2-menthene and 3-menthene.

Problem 29.12 ls the pro-R or pro-5 hydrogen removed from citrate during the dehydration in step 2 of the citric acid cycle Does the elimination reaction occur with syn or anti geometry ... 

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. 

However, the E2C mechanism has been criticized, and it has been contended that all the experimental results can be explained by the normal E2 mechanism. McLennan suggested that the transition state is that shown as 18. An ion-pair mechanism has also been proposed. Although the actual mechanisms involved may be a matter of controversy, there is no doubt that a class of elimination reactions exists that is characterized by second-order attack by weak bases. " These reactions also have the following general characteristics (1) they are favored by good leaving groups (2) they are favored by polar aprotic solvents (3) the reactivity order is tertiary > secondary > primary, the opposite of the normal E2 order (p. 1319) (4) the elimination is always anti (syn elimination is not found), but in cyclohexyl systems, a diequatorial anti elimination is about as favorable as a diaxial anti elimination (unlike the normal E2 reaction, p. 1302) (5) they follow Zaitsev s rule (see below), where this does not conflict with the requirement for anti elimination. 

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