Regiochemistry of 1,2-Elimination Reactions

In the Elcb mechanism, the direction of elimination is governed by the kinetic acidity of the individual 6-protons, which in turn is determined by the polar and 

Comparison of the data for methoxide with those for t-butoxide in Table 5.11 illustrates a second general trend. Stronger bases favor formation of the less-substituted alkene. A stronger base leads to an increase in the carbanion character at the TS and, thus, shifts it in the Elcb direction. A correlation between the strength of the 

Leaving group Base/solvent Product Composition  

The direction of elimination is also affected by steric effects, and if both the base and the reactant are highly branched, steric factors may lead to preferential removal of the less hindered hydrogen. Thus, when 4-methyl-2-pentyl iodide reacts with very hindered bases such as potassium tricyclohexylmethoxide, there is preferential formation of the terminal alkene. In this case, potassium f-butoxide favors the internal alkene, although by a smaller ratio than for less branched alkoxides. 

Base (K+salt) p T(DMSO) 2-Iodobutane 2-Butyl tosylate  

In the El mechanism, the leaving group has completely ionized before C—H bond breaking occurs. The direction of the elimination therefore depends on the structure of the carbocation and the identity of the base involved in the proton transfer that follows C—X heterolysis. Because of the relatively high energy of the carbocation intermediate, quite weak bases can effect proton removal. The solvent m often serve this function. The counterion formed in the ionization step may also act as the proton acceptor  

In the El cb mechanism, the direction of elimination is governed by the kinetic acidity of the individual p protons, which, in turn, is determined by the polar and resonance effects of nearby substituents and by the degree of steric hindrance to approach of base to the proton. Alkyl substituents will tend to retard proton abstraction both electronically and sterically. Preferential proton abstraction from less substituted positions leads to the formation of the less substituted alkene. This regiochemistry is opposite to that of the El reaction. 

Substrate Base, solvent Percent composition of alkene  

CHjCHzCHzCHz HCHs Base, solvent 1-Hexene 2-Hexene irons cis  

Many substrates have nonequivalent /3-protons, so a 1,2-elimination may produce more than one alkene. For example, ethoxide-promoted elimination of 2-iodo-3-methylbutane produced 82% of 2-methyl-2-butene and 18% of 3-methy 1-1-butene (equation 10.34). The generalization that 1,2-elimination reactions of alkyl halides usually give the more substituted alkene is known as the Saytzeff rule. Saytzeff observed that the regiochemistry of elimination could be correlated with removal of a hydrogen atom from the 

Failure to observe syn stereochemistry in an enzyme-catalyzed 1,4-elimination suggested that the enzyme-catalyzed reaction is a two-step process and not a concerted reaction (a) Hill, R. K. Newkome, G. R.. Am. Chem. Soc. 1969,91,5893 (b) Onderka, D. K. Floss, H. G. /. Am. Chem. Soc. 1969, 91, 5894. 

The Saytzeff rule applies to both El and E2 reactions. For example, the reaction of f-amyl bromide (11) with 0.05 M sodium ethoxide in ethanol at 25°C was found to occur by competing El and E2 pathways. Both the El and E2 reactions produced higher yields of 2-methyl-2-butene (12) than of 2-methyl-l-butene (13). The percent yield of 12 was found to be 71% by the E2 pathway and 82% by the El pathway. The percent of 2-methyl-2-butene decreases with increasing concentration of ethoxide in the reaction mixture because a greater portion of the product is formed by the E2 reaction.  

Saytzeff, A. Liebigs Ann. Chem. 1875, 179, 296. See also the discussion in reference 3. The reaction produced a total of 56% elimination and 44% substitution. 

Reaction coordinate diagram for dehydrobromination of 2-bromo-butane to 1-butene and 2-butene with Saytzeff orientation. 

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Here is where we get back to mechanisms. Whether we are talking about Zaitsev vs. Hoffman elimination reactions or about Markovnikov vs. anti-Markovnikov addition reactions, the explanation of the regiochemistry for every reaction is contained within the mechanism. If we completely understand the mechanism, then we will understand why the regiochemistry had to be the way it turned out. By understanding the mechanism, we eliminate the need to memorize the regiochemistry for every reaction. With every reaction you encounter, you should consider the regiochemistry of the reaction and look at the mechanism for an explanation of the regiochemistry. 

Another problem that occurs with eliminations is the regiochemistry of the reaction. As we saw in Chapter 9, most eliminations follow Zaitsev s rule and produce the more highly substituted alkene as the major product. However, a significant amount of the less highly substituted product is also formed. In addition, mixtures of ds and trans isomers are produced when possible, further complicating the product mixture. Because separating a mixture of such isomers is usually a difficult task, elimination reactions are often not the best way to prepare alkenes. (Other methods will be described in subsequent chapters.) However, if only one product can be formed, or if one is expected to greatly predominate in the reaction mixture, then these elimination reactions can be quite useful. 

Follow the steps listed in the preceding Visual Summary of Key Reactions section. Identify the leaving group, the electrophilic carbon, and the nucleophile (or base). Then determine which mechanism is favored (see Section 9.7). Watch out for stereochemistry where important, regiochemistry in elimination reactions, and carbocation rearrangements when the mechanism is SN1 or El. 

The regiochemistry of this reaction is reminiscent of die related selenoxide elimination since it mainly leads to the less-substituted alkene (Scheme 63).However, striking differences exist in the case of 1-octylcyclobutyl methyl selenide, where the reaction regioselectively produces octylidenecyclobutane via the ylide route (Scheme 64, a), whereas a 1 1 mixture of octylidenecyclobutane and 1-octylcyclo-butene is formed via the selenoxide route (Scheme 64, b). ... 

The regiochemistry of the reaction establishes that it generally involves a 1,1- rather than a 1,3-elimination. 

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... 

DeShong (Scheme 20). Thus, reaction of nitrones with vinyl silanes followed by reduction provides Peterson - type intermediates which can then be eliminated to either Z- or E-products. Homoallylic amines were also prepared using allylsilane in the initial cycloaddition. Substitution reactions of allylic nitro compounds have received considerable attention and some examples are outlined in Scheme 21. In each case, examination of the regiochemistry of the reaction was of paramount concern, the results using palladium being superior to the SnCl mediated process. Allylic sulphides constitute yet another group of... 

We can now readily deduce the regiochemistry of elimination for 10.8 the reaction goes through an ElcB mechanism because the intermediate enolate anion is easily formed. 

The nature of the transition state in elimination reactions is of great importance, since it controls the regiochemistry of p elimination in compounds in which the double bond can be introduced in one of several positions. These effects are discussed in the next section. 

Elimination reactions are more complex than substitution reactions for several reasons. There is, for example, the problem of regiochemistry. What... 

The regiochemistry of this elimination reaction resembles that observed by Davis et al. (see Scheme 9) [23]. The special nature of the bonds in three-mem-bered rings is probably responsible for this exclusive regiochemistry. It is of interest to note that 3,3-dimethylaziridine-2-carboxylic ester indeed leads to the corresponding 3H-azirine ester upon Swern oxidation here there is, of course, no choice. 

The regiochemistry of the Heck reaction is determined by the competitive removal of the (3-proton in the elimination step. Mixtures are usually obtained if more than one type of (3-hydrogen is present. Often there is also double-bond migration that occurs by reversible Pd-H elimination-addition sequences. For example, the reaction of cyclopentene with bromobenzene leads to all three possible double-bond isomers.146... 

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