E2 and ElcB

We have previously discussed (Chapter 5) that the formation of a double-bond from a carbonium ion requires that the bond to the hydrogen on the adjacent carbon should be parallel to the p-orbital of the positively charged carbon atom. This topic will not be further discussed in this Chapter which is concerned with double-bond formation under basic conditions. 

In principle, stereoelectronic effects should play an important role in the formation of double-bonds in base-promoted eliminations of HX. 

This reaction can take place by either a step-wise or a concerted mechanism. In the non-concerted mechanism (ElcB), the C —H bond is ruptured prior to the scission of the C— X bond. Thus, strong stereoelectronic effects should be observed depending on the relative orientation of the electron pair and the C —X bond in 283 indeed, when the electron pair is oriented antiperi-planar to the C —X bond, it should ease the formation of the double-bond. 

A great deal of experimental results have been rationalized on that basis for instance, compound 284 gives only the olefin 2B6 via an anti process while the isomer 285 gave a mixture of olefin 286 (syn mode) and 287 (anti mode). 

This result has been clearly explained by Bartsch and Zavada as quoted from  

---

The mechanistic borderline between E2 and ElcB mechanisms has been studied under various conditions.1,2 The mechanism of the elimination reaction of 2-(2-fluoroethyl)-1-methylpyridinium has been explored explored by Car-Parrinello molecular dynamics in aqueous solution.3 The results indicated that the reaction mechanism effectively evolves through the potential energy region of the carbanion the carbon-fluoride bond breaks only after the carbon-hydrogen bond. 

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. 

The mechanism by which proton acids catalyze the dehydration of primary and secondary alcohols in water is not perfectly well understood (1). There is universal agreement that the dehydration of tertiary alcohols can be explained by an El mechanism (1,2) involving either a II complex ( ) or a symmetrically solvated carbonium ion (4) as the key reaction intermediate. Although an occasional text ( ) also describes the dehydration of primary alcohols by an El mechanism, authoritative reviews (1/4) conclude that a concerted E2 type mechanism is more probable. The dehydration behavior of secondary alcohols is presumed to be similar to primary alcohols (4). Discussions of the gas phase dehydration of alcohols by heterogeneous Lewis acid catalysts admit more possibilities. In their authoritative review Kut, et al. (1) consider E1-, E2-, and ElcB-like mechanisms, as well as the possible role of diethyl ether as a reaction intermediate, but they reach no conclusion concerning the relative importance of these mechanisms in the formation of olefins from alcohols. 

Substitution by the SN2 mechanism and -elimination by the E2 and Elcb mechanisms are not the only reactions that can occur at C(sp3)-X. Substitution can also occur at C(sp3)-X by the SRN1 mechanism, the elimination-addition mechanism, a one-electron transfer mechanism, and metal insertion and halogen-metal exchange reactions. An alkyl halide can also undergo a-elimination to give a carbene. 

Use of Model Alcohols in Mechanistic Studies. - Much use has been made of model alcohols of various types in order to elucidate the detailed mechanism of dehydration, and in so doing, most catalysts have been compared with either alumina or thoria representing respectively E1/E2 and ElcB mechanisms. 

Abstract This chapter emphasises on the important aspects of steric and stereo-electronic effects and their control on the conformational and reactivity profiles. The conformational effects in ethane, butane, cyclohexane, variously substituted cyclohexanes, and cis- and tra/ ,v-decalin systems allow a thorough understanding. Application of these effects to E2 and ElcB reactions followed by anomeric effect and mutarotation is discussed. The conformational effects in acetal-forming processes and their reactivity profile, carbonyl oxygen exchange in esters, and hydrolysis of orthoesters have been discussed. The application of anomeric effect in 1,4-elimination reactions, including the preservation of the geometry of the newly created double bond, is elaborated. Finally, a brief discussion on the conformational profile of thioacetals and azaacetals is presented. 

Fig. 5.12. Two-dimensional potential energy diagrams depicting El, E2, and Elcb mechanisms.

Chapter 5 considers the relationship between mechanism and regio- and stereoselectivity. The reactivity patterns of electrophiles such as protic acids, halogens, sulfur and selenium electrophiles, mercuric ion, and borane and its derivatives are explored and compared. These reactions differ in the extent to which they proceed through discrete carbocations or bridged intermediates and this distinction can explain variations in regio- and stereochemistry. This chapter also describes the El, E2, and Elcb mechanisms for elimination and the idea that these represent specific cases within a continuum of mechanisms. The concept of the variable mechanism can explain trends in reactivity and regiochemistry in elimination reactions. Chapter 6 focuses on the fundamental properties and reactivity of carbon nucleophiles, including... 

Fig. 1. Free energy profile for E2 and ElcB reactions. (Reproduced with permission from...

We have discussed in this chapter that it is sometimes difficult to distinguish E2 and ElcB mechanisms by examining kinet-... 

Another factor that complicates a study of elimination reactions is that they can take place hy different mechanisms, just as substitutions can. We ll consider three of the most common mechanisms—the El, E2, and ElcB reactions— which differ in the timing of C-H and C-X bond-breaking. 

Among the different types of elimination processes only bimolecular pathways will be in agreement with Eq. 12.1 and hence we will center the discussion on E2 and ElcB mechanisms. Prior to flie discussion of flie experimental data, it may be necessary to talk about the main features of the E2 and ElcB reactions in detail. 

Apparently the hypothesis of a nucleophile-catalyzed reaction fits well with all the experimental data. However, there is still an additional question being the transformation of zwitterion 7 into the Baylis-Hillman product 3. Intermediate 7 may evolve to compound 3 either by an E2 or by an ElcB elimination process (Scheme 32.6). Based on experimental evidence, we only know that the fission of the vinylic a-proton should occur at some stage after the rate-determining step, because no deuterium KIE is detected. Only with this data in hand, it is impossible to decide between the E2 and ElcB elimination processes (Scheme 32.6). 

Three possible mechanisms of P-elimination (El, E2 and ElcB) could be considered to explain the base-promoted HF elimination from 4-fluoro-4-(4 -nitro-... 

The transition states of the E2 and ElcB mechanisms are represented in Fig. 37.3 together with the KIEs that should be observed in each case. Just by comparing the three transition states, it becomes clear that no primary D KIE should be observed in the (E1cB)r mechanism, as the proton has been already removed. As the experimental fact is a clear primary D KIE at C3, the EIcBr mechanism must be discarded. Additionally it is an experimental fact that no H/D exchange with the solvent has been observed in the elimination of substrates 1. Solvent H/D exchange is indicative for an EIcBr mechanism where the carbanion is reprotonated by the solvent in the fast initial step (see equation C in Scheme 37.2). 

All these arguments leave us with the E2 and (ElcB)irr alternatives, both in good agreement with the observed primary D KIEs at C3 (D colored red) and secondary D KIEs at C4 (D colored blue) (Fig. 37.3). 

The El process is very unlikely vinyl cations are quite unstable. Both E2 and ElcB are viable options vinyl anions are reasonably stable (remember the orbital effect in considering anion stability). 

---