Allylic carbon bromination

Allylic bromides can also serve as progenitors for nucleophilic organochromium reagents. An elegant example is found in Still and Mobilio s synthesis of the 14-membered cembranoid asperdiol (4) (see Scheme 2).7 In the key step, reduction of the carbon-bromine bond in 2 with chromium(n) chloride in THF is attended by intramolecular carbonyl addition, affording a 4 1 mixture of cembranoid diastereoisomers in favor of the desired isomer 3. Reductive cleav-... 

The group ofWalborsky probably has described one of the first true anionic/radi-cal domino process in their synthesis of the spirocyclopropyl ether 2-733 starting from the tertiary allylic bromide 2-730 (Scheme 2.161) [369]. The first step is a Michael addition with methoxide which led to the malonate anion 2-731. It follows a displacement of the tertiary bromide and a subsequent ring closure which is thought to involve a SET from the anionic center to the carbon-bromine anti bonding orbital to produce the diradical 2-732 and a bromide anion. An obvious alternative Sn2 halide displacement was excluded due to steric reasons and the ease with which the reaction proceeded. 

The relative stabilities of radicals follow the same trend as for carhoca-tions. Like carbocations, radicals are electron deficient, and are stabilized by hyperconjugation. Therefore, the most substituted radical is most stable. For example, a 3° alkyl radical is more stable than a 2° alkyl radical, which in turn is more stable than a 1° alkyl radical. Allyl and benzyl radicals are more stable than alkyl radicals, because their unpaired electrons are delocalized. Electron delocalization increases the stability of a molecule. The more stable a radical, the faster it can be formed. Therefore, a hydrogen atom, bonded to either an allylic carbon or a benzylic carbon, is substituted more selectively in the halogenation reaction. The percentage substitution at allylic and benzyhc carbons is greater in the case of bromination than in the case of chlorination, because a bromine radical is more selective. 

This reaction is unique because it permits one to place a bromine atom on a molecule containing an olefin linkage and the product retains the C=C. For this reaction to take place there must always be a H on an a— or allylic carbon (carbon adjacent to OC). This is the H that is replaced by the Br. If there are several a-carbons each containing H, then the Br may go to any of the a-carbons, i.c.,... 

Halogenation at an allylic carbon often results in a mixture of products. For example, bromination of 1-butene under radical conditions forms a mixture of 3-bromo-1 -butene and 1-bromo-2-butene. 

The evolution of HBr in the bromination reactions and the uptake of one bromine atom per ring indicate substitution at a secondary allylic carbon atom. The ease of oxidation and cross linking of the polymers and the presence of hydroxyl groups imply the intermediate formation of hydroperoxides on allylic carbon atoms. Treatment of the hydroxyl-containing polymer with benzoyl chloride indicates that the bulk of the hydroxyl groups are on secondary carbon atoms, since tertiary hydroxyl groups would tend to be replaced by chlorine. Although these results do not permit the elimination of structure B, it appears that the bulk of the structural units in the polycyclopentadiene corresponds to 1,2- addition (A). 

In contrast to light and heat, it is possible to initiate a reaction using a compound that spontaneously forms radicals. For example, a very useful synthetic radical reaction is the bromination of an allylic carbon using N-bromosuccinimide, NBS. This reaction exemplifies the third manner in which radical reactions may be initiated. This reaction will not start unless there is a trace of a radical initiator, In This may be the result of some impurity, such as a small amount of a peroxide, which readily decomposes to form a radical. This initial radical, In, then reacts with traces of bromine or HBr molecules to form bromine atoms. These then abstract the allylic hydrogen from the alkane, R-H. Write down the steps that have been considered so far. 

We know that the more stable the radical, the faster it can be formed. This means that a hydrogen bonded to either a benzylic carbon or an allylic carbon will be preferentially substituted in a halogenation reaction. As we saw in Section 9.4, bromination is more highly regioselective than chlorination, so the percent of substitution at the benzylic or allylic carbon is greater for bromination. 

Another common reaction of alkenes uses diatomic halogens such as bromine (Br2) to form 1,2-dibromides (see Chapter 10, Section 10.4.1). In this reaction, the alkene reacts as a Lewis base with the bromine atom to form a bromonium ion. When 1,3-butadiene (3) reacts with bromine, both 1,2 and 1,4 addition products are formed, just as with the HBr reaction. The products are 3,4-dibromo-l-butene (32) and a mixture otE- and Z-l,4-dibromo-2-butene (33 and 34). Initial reaction with bromine gives bromonium ion 29 however, when this reacts with bromide ion, there are two sites for reaction. If bromide attacks the less stericaUy hindered carbon atom, the product is 32, but the bromine ion may also attack the C=C unit to give products 33 + 34. Nucleophilic attack of this type is called an Sj reaction (nudeophilic substitution at an allylic carbon with displacement of the leaving group). 

Ionization of the carbon-bromine bond forms a resonance-stabilized 2° allylic car-bocation. Acetic acid is a poor nucleophile, which reduces the likelihood of an S j2 reaction. Further, acetic acid is a moderately polar protic (hydroxylic) solvent that favors Sjjl reaction. From this analysis, we predict that this reaction occurs by an 8, 1 mechanism and both enantiomers of the product are observed. 

AT-Bromosuccinimide (NBS) is frequently used to brominate allylic carbons because it allows a radical substitution reaction to be carried out in the presence of a low concentration of Br2 and a low concentration of HBr. If a high concentration is present, addition of Bt2 or HBr to the double bond will compete with allylic substitution. 

A racemic mixture is also obtained if a hydrogen bonded to an asymmetric center is substituted by a halogen. A-Bromosuccinimide (NBS) is used to brominate allylic carbons. 

Alkenes undergo radical substitution at allylic carbons. NBS is used for bromination at allylic carbons (Section 13.9). The mechanism of the reaction is shown on page 574. 

In the presence of bismuth(lll) chloride-aluminum, allylic bromides have been found to react with aldehydes at room temperature in tetrahydrofuran-water to afford the corresponding homoallyhc alcohols in high yields (Wada et al, 1987). Water was found to play a crucial role since the allylation failed in pure tetrahydrofuran. Only a catalytic amount of bismuth chloride was needed to carry out the reaction. Bismuth(ill) chloride was reduced by aluminum to zero-valent bismuth, which could insert into the carbon-bromine bond of the allylic bromide to afford an allylbismuth intermediate as the reactive species. The allylation reaction could occur with the couple Bi(0)-Al(0) in tetrahydrofuran-water only in the presence of a catalytic amount of hydrobromic acid (Wada et al, 1990). Since bismuth(O) was postulated to be an intermediate oxidation state, the reaction was accomplished via an electrochemical redox pathway (Figure 4.1) in a two-phase system (Minato and Tsuji, 1988). Reactions mediated by Bi(0) as the only promotor were sluggish (Wada et ah, 1990). An exception was, however, reported with the coupling between p-nitrobenzaldehyde and allyl iodide in water (Chan and Isaac, 1996). 

In summary, the initial formation of an allylic radical anion on the metal surface is the most likely event, which would explain the success of indium, as its first ionization potential is particularly low E - 5.79 eV). In tin- and indium-mediated reactions the second step should be the insertion of the metal cation into the carbon-bromine (chlorine) bond to afford organometallic intermediates, which are stable enough to be produced, but also highly reactive toward carbonyl compounds in aqueous media. 

First, draw the structure of the resonance-stabilized allylic carbocation that forms when the carbon-bromine bond breaks. Second, draw the structures of the resonance-stabilized allylic carbocation. Third, add a bromide ion to the carbocation to obtain the isomeric bromine compound whose ionization would give the same resonance-stabilized carbocation. 

The photocychzation of the Diels-Alder e do-adducts of cyclic dienes with p-benzoquinone has been successfully applied to the construction of polycyclic cages. Nair et al. reported that the photocychzation of the 2,5-bis(bromomethyl) compound 47 gave the unexpected cage compound 49 as a major product along with the anticipated product 48 (Scheme 9)." The formation of 49 can be explained through the initial photolytic cleavage of the bromine-allylic carbon bond (50) followed by radical reorganization and final bromine radical capture. 

A white solid, m.p. 178 C. Primarily of interest as a brominaling agent which will replace activated hydrogen atoms in benzylic or allylic positions, and also those on a carbon atom a to a carbonyl group. Activating influences can produce nuclear substitution in a benzene ring and certain heterocyclic compounds also used in the oxidation of secondary alcohols to ketones. 

The basic premise for making bromosafrole has been to mix sa-frole with Hydrobromic Acid (a.k.a. hydrogen bromide, HBr). That s it. The HBr does what is called a Markovnikov addition reaction whereby the HBr sees the allyl double bond of safrole and preferentially attaches its hydrogen to the gamma carbon and its bromine to the middle beta carbon (don t ask). 

Neutral HX addition X = P, S, Se, Si Allylic bromination Carbon-halogen addition... 

As we saw when discussing allylic bromination in Section 10.4, A-bromosuccin-imide (NBS) is a convenient free-radical brominating agent. Benzylic brominations with NBS are nonnally perfonned in carbon tetrachloride as the solvent in the presence of peroxides, which are added as initiators. As the exanple illustrates, free-radical bromination is selective for substitution of benzylic hydrogens. 

Olefins react with bromine by addition of the latter to the carbon-carbon double bond. In contrast the Wohl-Ziegler bromination reaction using N-bromosuccinimide (NBS) permits the selective substitution of an allylic hydrogen of an olefinic substrate 1 by a bromine atom to yield an allylic bromide 2. 

When the allylic cation reacts with Br to complete the electrophilic addition, reaction can occur either at Cl or at C3 because both carbons share the positive charge (Figure 14.4). Thus, a mixture of 1,2- and 1,4-addition products results. (Recall that a similar product mixture was seen for NBS bromination of alkenes in Section 10.4, a reaction that proceeds through an allylic radical.)... 

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