Unsymmetric alkenes

Let s compare the carbocation intermediates for addition of a hydrogen halide (HX) to an unsymmetrical alkene of the type RCH=CH2 (a) according to Markovnikov s rule and (b) opposite to Markovnikov s rule (a) Addition according to Markovnikov s rule... 

The addition of hydrogen halides to alkenes has been studied from a mechanistic point of view over a period of many years. One of the first aspects of the mechanism to be established was its regioselectivity, that is, the direction of addition. A reaction is described as regioselective if an unsymmetrical alkene gives a predominance of one of the two possible addition products the term regiospecific is used if one product is formed... 

As will be indicated when the mechanism is discussed in more detail, discrete carbocations may not be formed in all cases. An unsymmetrical alkene will nevertheless follow Markownikoff s rule, because the partial positive charge that develops will be located preferentially at the carbon that is better able to accommodate the electron deficiency, that is, the more substituted one. 

This mechanism explains the observed formation of the more highly substituted alcohol from unsymmetrical alkenes (Markownikoff s rule). A number of other points must be considered in order to provide a more complete picture of the mechanism. Is the protonation step reversible Is there a discrete carbocation intermediate, or does the nucleophile become involved before proton transfer is complete Can other reactions of the carbocation, such as rearrangement, compete with capture by water ... 

Markovnikov s rule is used to predict the regiochemistry of HX (electrophilic) addition reactions. The rule states that HX adds to an unsymmetrical alkene mainly in the direction that bonds H to the less substituted alkene carbon and X to the more substituted alkene carbon. 

One of the features that makes the hydrobora ( ion reaction so useful is the regiochemistry that results when an unsymmetrical alkene is hydroborated. For example, hydroboration/oxidation of 1-methylcyclopentene yields trans-2-methylcydopentanol. Boron and hydrogen both add to the alkene from the same face of the double bond—that is, with syn stereochemistry, the opposite of anti—with boron attaching to the less highly substituted carbon. During the oxidation step, the boron is replaced by an -OH with the same stereochemistry, resulting in an overall syn non-Markovnikov addition of water. This stereochemical result is particularly useful because it is complementary to the Markovnikov regiochemistry observed for oxymercuration. 

In addition to its effect on stability, delocalization of the unpaired electron in the allyl radical has other chemical consequences. Because the unpaired electron is delocalized over both ends of the nr orbital system, reaction with Br2 can occur at either end. As a result, allylic bromination of an unsymmetrical alkene often leads to a mixture of products. For example, bromination of 1-octene gives a mixture of 3-bromo-l-octene and l-bromo-2-octene. The two products are not formed in equal amounts, however, because the intermediate allylic radical is... 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

Unsymmetrical alkenes can be prepared from a mixture of two ketones, if one is in excess. " The mechanism consists of initial coupling of two radical species to give a 1,2-dioxygen compound (a titanium pinacolate), which is then deoxygenated. " ... 

Allylic bromination of unsymmetrical alkenes may give many products. Occasionally one product is formed in reasonable yield, e.g. (3), but this is a matter for trial and error. 

The bottom line is regiochemistry is only relevant when adding two dijferent groups across an unsymmetrical alkene. 

In other words, we must determine whether the reaction is a Markovnikov addition or an anii-Markovnikov addition. As promised, the answer to this question is contained in the mechanism. In the first step of the mechanism, a proton was transferred to the alkene, to form a carbocation. When starting with an unsymmetrical alkene, we are confronted with two possible carbocations that can form (depending on where we place the proton) ... 

In the absence of water, we did not need to think about regiochemistry, because we were adding Br and Br. But now, in the presence of water, we are adding Br and OH (two different groups). As a result, the regiochemistry will be relevant if we start with an unsymmetrical alkene—for example,... 

The regioselective hydrozirconahon of internal unsymmetrical alkenes remains a challenge, as it could considerably expand the use of zirconocene complexes. Little is known about the mechanism of zirconium migration along an alkyl chain. 

Both unsymmetrical alkenes and diols can be prepared by applying these methods to mixtures of two different carbonyl compounds. An excess of one component can be used to achieve a high conversion of the more valuable reactant. A mixed reductive... 

Oxymercuration/demercuration provides a milder alternative for the conventional acid-catalyzed hydration of alkenes. The reaction also provides the Markovnikov regiochemistry for unsymmetrical alkenes.33 Interestingly, an enantioselective/inverse phase-transfer catalysis (IPTC) reaction for the Markovnikov hydration of double bonds by an oxymercuration-demercuration reaction with cyclodextrins as catalysts was recently reported.34 Relative to the more common phase-transfer... 

Addition is initiated by the positively polarised end (the less electronegative halogen atom) of the unsymmetrical molecule, and a cyclic halonium ion intermediate probably results. Addition of I—Cl is particularly stereoselective (ANTI) because of the ease of formation (and relative stability compared with carbocations) of cyclic iodonium ions. With an unsymmetrical alkene, e.g. 2-methylpropene (32), the more heavily alkyl-substituted carbon will be the more carbocationic (i.e. the less bonded to Br in 33), and will therefore be attacked preferentially by the residual nucleophile, Cle. The overall orientation of addition will thus be Markownikov to yield (34) ... 

The regioselectivity of the addition of HX to an unsymmetrical alkenes i) The addition of HBr to propene the main product is 2-bromopropane. 

If an unsymmetrical alkene combines with a hydrogen halide, the halide ion adds to the carbon atom with fewer hydrogen atoms (The addition of HX to an alkene, the hydrogen atom adds to the carbon atom of the double that already has the greater number of hydrogen atoms). 

The step 1 of the addition reaction of HX to an unsymmetrical alkene could conceivably lead to two different carbocations ... 

With unsymmetrical alkenes, Markownikoff s rule is applied. On addition of H-X, the hydrogen atom adds to the carbon atom which already has the more hydrogen atoms directly bonded to it. Applying the rule results in 2-bromopropane as the major product below. 

Infrared and Raman spectra. The infrared spectra of cis-trans isomers of unsymmetrical alkenes of the type R-CH=CH-R show characteristic differences... 

We have just seen that when H-H or Br-Br or H-Br or H-OH is added to but-2-ene, only one product is formed. However, when a hydrogen halide or water is added to an unsymmetrical alkene, i.e. one in which the groups attached to one carbon of the double bond are not identical to the groups attached to the other carbon atom, two products are formed. For example, when hydrogen chloride is added to the unsymmetrical alkene but-l-ene, both 2-chlorobutane and 1-chlorobutane are formed ... 

You will remember that, when a hydrogen halide reacts with an unsymmetrical alkene, such as propene, two products are formed 2-bromopropane and 1-bromopropane. 

Fields et al. showed that a variety of unsymmetrical alkenes added regiospecifically to the acridizinium nucleus and pointed out that the great majority of cases could be rationalized by the assumption that the more negatively polarized end of the alkene was preferentially attracted toward position 6, the previously demonstrated center for nucleophilic attack on the acridizinium ring. At the same time they reported that the addition of acrylonitrile to yield a 12- rather than a 13-cyano adduct is the reverse of what would be expected from the polarization of the acrylonitrile molecule. Possible explanations for this exception are offered in Section V. 

The addition of alkenes to A -methylenium amide cations is stereo-specific in the sense that it obeys the cis principle of Alder and Stein, cis-2-butene giving a cis product (105, R = R = Me) and the trans isomer giving trans product (105, R = R = Me). The cycloaddition of unsymmetrical alkenes is highly regiospecific. Knowing how the alkene will react with a large cation allows prediction of the product (105). Thus styrene, butadiene, and vinyl acetate all react so that its substituent appears at position 6 of the dihydrooxazinium salt (105, R = Ph, vinyl, or OAc). 

While monosubstituted alkenes usually react with high regioselectivity, it is not true for disubstituted alkenes. Formation of mixtures of type 163 and 164 (equation 105) has been observed in most cases when unsymmetrical alkenes bearing two different substituents possess similar stereoelectronic properties. In general, regioselectivity is controlled by a combination of HOMO-LUMO interactions, steric effects and hydrogen bonding between suitable substituents in both alkene and nitrone molecules . ... 

The term regioselective is used to describe addition reactions that proceed selectively in one direction with unsymmetrical alkenes.1 Markownikoff s rule describes a specific case of regioselectivity that is based on the stabilizing effect that alkyl and aryl substituents have on carbocations. 

---