The Regioselectivity of E2 Eliminations

If a Ctert—H were present, it would not react at all. As a consequence, the Hofmann product is produced predominantly, but not exclusively. 

Many cyclohexane derivatives undergo—in apparent contradiction to what has been said before—perfectly Hofmann-selective E2 eliminations even when they contain good leaving 

Side Note 4.1 Regioselectivity of HBr Elimination from fr s-l,2-Dibromocyclo-hexane 

0 9 Br bond dipoles are oriented antiparallel and thus able to avoid repulsion). If this chair conformer eliminates HBr, the dihedral angle between the C-H and the SC-Br that are to be broken on the way to 3-bromocyclohexene measures a favorable 180°. the dihedral angle between the H and Br atoms to be eliminated to afford 1 -bromocyclohexene is an unfavorable 60°. As long as the reaction temperature is not too low and/or the potassium alkoxide not too undemanding sterically so that ether formation by the SN2 mechanism becomes competitive, the 3-bromocyclohexene eliminates a second equivalent of HBr in another 1,2-elimination, forming 1,3-cyclohexadiene. 

Here are two deceptively similar elimination reactions. The leaving group changes and the reaction conditions are very different but the overall process is elimination of HX to produce one of two alkenes. 

In the first example acid-catalysed elimination of water from a tertiary alcohol produces a Lrisub-stitued alkene. Elimination of HCl from the corresponding tertiary alkyl chloride promoted by a very hindered alkoxide base (more hindered than f-BuOK because all the ethyl groups have to point away from one another) gives exclusively the less stable disubstituted alkene. 

Anion-stabilizing groups allow another mechanism—ElcB 

Traditionally, these two opposite preferences—for the more or the less substituted alkenes—have been called Saytsev s rule and Hofmann s rule, respectively. You will see these names used (along with a number of alternative spellings—acceptable for Saytsev, whose 

This detacatized anion is caMed an enotate, and vva wilt dl uss enotates in moredetaiHn Chapter 21 and beyond. 

The reason for the two different regioselectivities is a change in mechanism. As we have already discussed, acid-catalysed elimination of water from tertiary alcohols is usually El, and you already know the reason why the more substituted alkene forms faster in El reactions (p. 394). It should come as no surprise to you now that the second elimination, with a strong, hindered base, is an E2 reaction. But why does E2 give the less substituted product This time, there is no problem getting C-H bonds anti-periplanar to the leaving group in the conformation 

Traditionally, these two opposite preferences—for the more or the less substituted alkenes—have been called Saytsev s rule and Hofmann s rule, respectively. You will see these names used (along with a number of alternative spellings— acceptable for Saytsev, whose name is transliterated from Russian, but not for Hofmann this Hofmann had one f and two n s), but there is little point remembering which is which (or how to spell them)—it is far more important to understand the reasons that favour formation of each of the two alkenes. 

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The regioselectivity of elimination is accommodated m the E2 mechanism by noting that a partial double bond develops at the transition state Because alkyl groups... 

Quaternary ammonium hydroxides un dergo elimination on being heated It is an anti elimination of the E2 type The regioselectivity of the Hofmann elimina tion IS opposite to that of the Zaitsev rule and leads to the less highly substi tuted alkene... 

When tertiary halides are treated with base, they undergo E2 elimination. The regioselectivity of elimination of tertiary halides follows the Zaitsev rule. 

Further exploration of the regioselectivity of alkene formation in elimination reactions (ElcB anc E2). 

The regioselectivity of elimination is accommodated in the E2 mechanism by noting that a partial double bond develops at the transition state. Since alkyl groups stabilize double bonds, they also stabilize a partially formed tt bond in the transition state. The more stable aUcene therefore requires a lower energy of activation for its formation and predominates in the product mixture because it is formed faster than a less stable one. 

What is the regioselectivity of an E2 reaction In other words, what are the factors that dictate which of the two elimination products will be formed in greater yield ... 

We can understand the regioselectivity of the Hofmann elimination by comparing steric effects in the E2 transition states for formation of 1-butene and trans-2-... 

FIGURE 7.88 The regioselectivity of the E2 reaction depends on the identity of the leaving group. Leaving groups such as fluoride, ammonium (R3N ), and sulfonium (RjS ) lead to predominant Hofmann elimination, in which the less stable isomer is the major product. 

Dehydration of alcohols (Sections 5 9-5 13) Dehydra tion requires an acid catalyst the order of reactivity of alcohols IS tertiary > secondary > primary Elimi nation is regioselective and proceeds in the direction that produces the most highly substituted double bond When stereoisomeric alkenes are possible the more stable one is formed in greater amounts An El (elimination unimolecular) mechanism via a carbo cation intermediate is followed with secondary and tertiary alcohols Primary alcohols react by an E2 (elimination bimolecular) mechanism Sometimes elimination is accompanied by rearrangement... 

Fig. 4.21. Steric base effects on the Saytzeff/Hofmann selectivity of an E2 elimination. The small base EtO can attack the H atoms in both positions / to the leaving group, i.e., it does not matter whether the H atom is bound to a primary or secondary C atom. The regioselectivity therefore results only from product development control the thermodynamically more stable.

Because of the same necessity for anf/-selectivity, trans-1,2-dibromocyclohexane does not react to form 1-bromocyclohexene in the KOfBu-promoted HBr elimination (Figure 4.23). Instead 3-bromocyclohexene is produced through a fairly regioselective E2 elimination. In a subsequent fast 1,2-elimination, it loses a second equivalent of HBr. In this way 1,3-cyclohexadiene is produced. 

Although El reactions show some stereo- and regioselectivity, the level of selectivity in E2 reactions can be much higher because of the more stringent demands on the transition state for E2 elimination. We will come back to the most useful ways of controlling the geometry of double bonds in Chapter 31. 

This regioselectivity distinguishes a Hofmann elimination from other E2 eliminations, which form the more substituted double bond by the Zaitsev rule (Section 8.5). This result is sometimes explained by the size of the leaving group, N(CH3)3. In a Hofmann elimination, the base removes a proton from the less substituted, more accessible carbon atom, because the bulky leaving group on the nearby a carbon. 

P-Elimination can be subdivided into Het -Het elimination and Het -elimination. Three different modes of action, E1-, E2- and Elcb elimination are known. An elimination proceeds as syn-elimination if both substituents leave the molecule from the same side of the newly formed C=C double bond and as anti-elimination if the two substituents leave the molecule from different faces. In Het -H elimination, control of the regioselectivity is problematic if two atoms are present. This can lead to a mixture of the less-substituted alkene, the so-called Hofmann product, and the more highly substituted alkene, the so-called Saytzew product. These problems do not occur in Het -Het elimination. In many cases Het -Het eliminations are either syn- or anti-selective by their mode of action. High stereoselectivity is observed in these cases, if both the a- and the P-carbon are stereogenic centers. 

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