Hydrogen anti addition

MarkownikofT s rule The rule states that in the addition of hydrogen halides to an ethyl-enic double bond, the halogen attaches itself to the carbon atom united to the smaller number of hydrogen atoms. The rule may generally be relied on to predict the major product of such an addition and may be easily understood by considering the relative stabilities of the alternative carbenium ions produced by protonation of the alkene in some cases some of the alternative compound is formed. The rule usually breaks down for hydrogen bromide addition reactions if traces of peroxides are present (anti-MarkownikofT addition). 

The rate of addition depends on the concentration of both the butylene and the reagent HZ. The addition requires an acidic reagent and the orientation of the addition is regioselective (Markovnikov). The relative reactivities of the isomers are related to the relative stabiUty of the intermediate carbocation and are isobutylene 1 — butene > 2 — butenes. Addition to the 1-butene is less hindered than to the 2-butenes. For hydrogen bromide addition, the preferred orientation of the addition can be altered from Markovnikov to anti-Markovnikov by the presence of peroxides involving a free-radical mechanism. 

As in the case of hydrogen halide additions, this mode of attack should lead to anti addition. 

The stereochemistry of radical addition of hydrogen bromide to alkenes has been studied with both acyclic and cyclic alkenes. Anti addition is favored.This is contrary to what would be expected if the s[p- carbon of the radical were rapidly rotating or inverting with respect to the remainder of the molecule ... 

The preferred stereochemistry of addition to cyclic alkenes is anti The additions are not as highly stereoselective as hydrogen bromide addition, however. 

If the carbanion has even a short lifetime, 6 and 7 will assume the most favorable conformation before the attack of W. This is of course the same for both, and when W attacks, the same product will result from each. This will be one of two possible diastereomers, so the reaction will be stereoselective but since the cis and trans isomers do not give rise to different isomers, it will not be stereospecific. Unfortunately, this prediction has not been tested on open-chain alkenes. Except for Michael-type substrates, the stereochemistry of nucleophilic addition to double bonds has been studied only in cyclic systems, where only the cis isomer exists. In these cases, the reaction has been shown to be stereoselective with syn addition reported in some cases and anti addition in others." When the reaction is performed on a Michael-type substrate, C=C—Z, the hydrogen does not arrive at the carbon directly but only through a tautomeric equilibrium. The product naturally assumes the most thermodynamically stable configuration, without relation to the direction of original attack of Y. In one such case (the addition of EtOD and of Me3CSD to tra -MeCH=CHCOOEt) predominant anti addition was found there is evidence that the stereoselectivity here results from the final protonation of the enolate, and not from the initial attack. For obvious reasons, additions to triple bonds cannot be stereospecific. As with electrophilic additions, nucleophilic additions to triple bonds are usually stereoselective and anti, though syn addition and nonstereoselective addition have also been reported. 

Dimethylcyclohexene is an example of an alkene for which the stereochemistry of hydrogen chloride addition is dependent on the solvent and temperature. At —78° C in dichloromethane, 88% of the product is the result of syn addition, whereas at 0° C in ether, 95% of the product results from anti addition.8 Syn addition is particularly common with alkenes having an aryl substituent. Table 4.1 lists several alkenes for which the stereochemistry of addition of hydrogen chloride or hydrogen bromide has been studied. 

The stereochemistry of addition depends on the details of the mechanism. The addition can proceed through an ion pair intermediate formed by an initial protonation step. Most alkenes, however, react via a complex that involves the alkene, hydrogen halide, and a third species that delivers the nucleophilic halide. This termolecular mechanism is generally pictured as a nucleophilic attack on an alkene-hydrogen halide complex. This mechanism bypasses a discrete carbocation and exhibits a preference for anti addition. 

An anti addition of hydrogen atoms to the triple bond occurs when alkynes are reduced with lithium or sodium metal in ammonia or ethylamine at low temperatures. 

The larger (Z,Z)-l,5-cyclononadiene (169) reacts141 stereoselectively with PhSeCl in AcOH to give the substituted hydrindan 170 (equation 138). In consideration of the anti addition mode of selenenyl reagents to double bonds, the transannular reactions of 169 have been rationalized on the basis of the two reaction intermediates, 171 or 172, which are liable to place the PhSe- and AcO- groups in a cis- 1,4-relationship and trans to the bridgehead hydrogen (equation 139). The preferential formation of 170 has thus been attributed to the fact that the pathway via 172 should involve a boat transition state. 

Alkynes show the same reaction and again the product obtained is the anti isomer. After a suitable elimination from the metal the alkene obtained is the product of the anti addition. Earlier we have seen that insertion into a metal hydride bond and subsequent hydrogenation will afford the syn product. If we use BH4 as the nucleophile we can accomplish anti addition of a hydride. Thus, with the borohydride methodology and the hydrogenation route either isomer can be prepared selectively. 

This is followed by an anti addition reaction in which water is added to the new double bond, but in the reverse sense. The hydrogen retained throughout the process is shown with an asterisk. Note that we... 

In the catalytic hydrogenation, two new C—H a bonds are formed simultaneously from H atoms absorbed into the metal surface. Thus, catalytic hydrogenation is stereospecific, giving only the syn addition product. If the atoms are added on the same side of the molecule, the addition is known as syn addition. If the atoms are added on opposite sides of the molecule, the addition is called an anti addition. For example, 2-butene reacts with H2 in the presence of a metal catalyst to give n-butane. 

Furthermore, electrophilic anti addition of /V-(phenylselanyl)phthalimide in the presence of triethylamine tris(hydrogen fluoride) has been investigated using alkenes (Table 14)216 and alkynes.217... 

The electrophilic anti addition of benzeneselenenyl fluoride to C = C bonds has been performed in a one-pot reaction with, /V-(phenylselanyl)phthalimide/triethylamine tris(hydrogen fluoride) using disubstituted alkynes to give a-fluoro-/T(phenylselanyl)alkenes 4.217... 

The stoichiometric equivalents of halogen fluorides, i.e. chlorine monofluoride, bromine monofluoride and iodine monofluoride, have found a wide application in addition reactions to double bonds. The equivalents are obtained by reacting A -haloamides or free halogens in combination with hydrogen fluoride or its salts as the source of fluoride ions. The reactions proceed under mild conditions at — 80 to 20 "C in anhydrous hydrofluoric acid or diethyl ether, tetrahydro-furan, dichloromethane or chloroform mainly by electrophilic addition with Markovnikov-type regioselectivity (anti addition).26-28... 

In the first step, the pyrimidine is hydrogenated at the double bond by dihydrouracil dehydrogenase (EC 1.3.1.2) to a dihydropyrimidine (Scheme 1.6.2). The enzymes obtained from rat [4] and human [5] liver have been purified and characterized. They were later subjected to molecular cloning [6], The hydrogens are added to the double bond at the Si face of C5 and C6 in an anti-addition reaction. This was deduced from NMR spectra recorded from the isolated degradation products after administration of [5-2H]- and [6-2H]uracil and 2H20 to a mammalian enzyme system [7]. 

The mechanism for the addition of the hydrogen halides to alkenes proceeds through a carbocation intermediate. As was the case in the SN1 reaction, the nucleophile can approach the planar carbocation equally well from either side, so we expect that the products should result from a mixture of syn and anti addition. Indeed, this is often the case. Under some conditions, however, the stereochemisty results from predominant syn addition, whereas anti addition is the favored pathway under other conditions. This occurs because these reactions are often conducted in nonpolar solvents in which ion pair formation is favored. The details of how this may affect the stereochemistry of these reactions are complex. Fortunately, stereochemistry is not an issue in most of the reactions in which hydrogen halides add, including all the examples previously presented, because the carbon to which the proton is adding usually has at least one hydrogen already bonded to it. In such situations, syn addition and anti addition give identical products. Stereochemistry will be more important in some of the other reactions that are discussed later in this chapter. 

Figure 11.5 shows a mechanism that has been postulated for this reaction. First, an electrophilic mercury species adds to the double bond to form a cyclic mercurinium ion. Note how similar this mechanism is, including its stereochemistry and regiochemistry, to that shown in Figure 11.4 for the formation of a halohydrin. The initial product results from anti addition of Fig and OH to the double bond. In the second step, sodium borohydride replaces the mercury with a hydrogen with random stereochemistry. (The mechanism for this step is complex and not important to us at this time.) The overall result is the addition of H and OH with Markovnikov orientation. 

The simultaneous addition of boron and hydrogen to the double bond (as shown in Mechanism 8-6) leads to a syn addition Boron and hydrogen add across the double bond on the same side of the molecule. (If they added to opposite sides of the molecule, the process would be an anti addition.)... 

The best way of ensuring anti addition of hydrogen across any triple bond is to treat the alkyne with sodium in liquid ammonia. 

Scheme 3.17 Stereochemistry of the hydrogenation of tetrasubstituted ethylenes. a—syn addition of H2 b—anti addition of H2.

Hydrogen Halides. Hydrogen halides add to double bonds to form alkyl halides in high yield [71]. This spontaneous addition is usually second order in acid, suggesting that either dimers of the acid are involved or halide anions react with the acid/alkene adduct by an Ade3 mechanism. Depending on the acid and nucleophile involved, either syn or anti addition is possible [Eq. (26)]. 

The addition of hydrogen bromide to olefins in acetic acid has been the subject of two recent studies in which both the kinetics and the stereochemistry of the reaction were investigated. The predominance of Ad 3 mechanisms were proved, syn and anti additions taking place, the latter being favoured. Different types of transition states were postulated, depending on the olefins involved in each study, but they all involved simultaneous attack by HBr at one carbon and a second moiety (N = Br, HBr or AcOH) at the other ... 

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