The stereospecificity of the reactions you have just met is very good evidence that E2 reactions proceed through an anti-periplanar transition state. We know with which diastereoisomer we started, and we know which alkene we get, so there is no question over the course of the reaction. More evidence comes from the reactions of substituted cyclohexanes. You saw in Chapter 16 that substituents on cyclohexanes can be parallel with one another only if they are both axial. An equatorial C–X bond is anti-periplanar only to C–C bonds and cannot take part in an elimination. For mono-substituted cyclohexyl halides treated with base, this is not a problem because, although the axial conformer is less stable, there is still a significant amount present (see the table on p. 375), and elimination can take place from this conformer.

● For E2 elimination in cyclohexanes, both C–H and C–X must be axial.

These two diastereoisomeric cyclohexyl chlorides derived from menthol react very differently under the same conditions with sodium ethoxide as base. Both eliminate HCl but diastereoisomer A reacts rapidly to give a mixture of products, while diastereoisomer B (which differs only in the configuration of the carbon atom bearing chlorine) gives a single alkene product but very much more slowly. We can safely exclude E1 as a mechanism because the same cation would be formed from both diastereoisomers, and this would mean the ratio of products (although not necessarily the rate) would be the same for both.

The key to explaining reactions like this is to draw the conformation of the molecules. Both will adopt a chair conformation, and generally the chair having the largest substituent equatorial (or the largest number of substituents equatorial) is the more stable. In these examples the isopropyl group is most influential—it is branched and will have very severe 1,3-diaxial interactions if it occupies an axial position. In both diastereoisomers, an equatorial i-Pr also means an equatorial Me: the only difference is the orientation of the chlorine. For diastereo isomer A, the chlorine is forced axial in the major conformer: there is no choice because the relative configuration is fixed in the starting material. It’s less stable than equatorial Cl, but is ideal for E2 elimination and there are two protons that are anti-periplanar available for removal by the base. The two alkenes are formed as a result of each of the possible protons with a 3:1 preference for the more substituted alkene. For diastereoisomer B, the chlorine is equatorial in the lowest-energy conformation. Once again there is no choice. But equatorial leaving groups cannot be eliminated by E2: in this conformation there is no anti-periplanar proton. This accounts for the difference in rate between the two diastereoisomers. A has the chlorine axial virtually all the time ready for E2, while B has an axial leaving group only in the minute proportion of the molecules that hap pen not to be in the lowest-energy conformation, but that have all three substituents axial. The all-axial conformer is much higher in energy, but only in this confomer can Cl− be eliminated. The concentration of reactive molecules is low, so the rate is also low. There is only one proton anti-periplanar and so elimination gives a single alkene.

مواضيع ذات صلة

Distinguishing acid derivatives by carbon NMR is difficult

E1cB eliminations in context

Anion-stabilizing groups allow another mechanism—E1cB

The regioselectivity of E2 eliminations

E2 elimination from vinyl halides: how to make alkynes

E2 eliminations can be stereospecific

E2 eliminations have anti-periplanar transition states

E1 reactions can be stereoselective

The role of the leaving group

Substrate structure may allow E1

E1 and E2 mechanisms

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