Allylic carbon selective bromination

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. 

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. 

Addition of the dicyanomethyl radical to propadiene (la) occurs exclusively at Q (not shown in Scheme 11.8) [60]. On the other hand, methyl-substituted allenes, e.g. Id, undergo /3-selective reactions with 2-bromomalodinitrile (15). The significant /3-selectivity has been associated with the steric demand of the incoming radical 16, which favors addition to the sterically least hindered site at the diene Id to provide allylic radical 17. However, it seems likely that a stabilization of an intermediate allylic radical, e.g. 17, by methyl substituents contributes significantly to the observed regioselectivity of product formation. Trapping of intermediate 17 with bromine atom donor 15 proceeds at the least substituted carbon to afford allylic bromide 18. 

Although free-radical halogenation is a poor synthetic method in most cases, free-radical bromination of alkenes can be carried out in a highly selective manner. An allylic position is a carbon atom next to a carbon-carbon double bond. Allylic intermediates (cations, radicals, and anions) are stabilized by resonance with the double bond, allowing the charge or radical to be delocalized. The following bond dissociation enthalpies show that less energy is required to form a resonance-stabilized primary allylic radical than a typical secondary radical. 

SOLUTION The bromine radical will abstract a secondary allylic hydrogen from C-4 of 2-pentene in preference to a primary allylic hydrogen from C-1. The resonance contributors of the resulting radical intermediate have the same groups attached to the sp carbons so only one bromoalkene is formed. Because of the high selectivity of the bromine radical an insignificant amount of radical will be formed by abstraction of a hydrogen from the less reactive primary allylic position. 

We have seen (Section 4-13C) that bromination is highly selective, with only the most stable radical being formed. If there is an allylic position, the allylic radical is usually the most stable of the radicals that might be formed. For example, consider the free-radical bromination of cyclohexene. Under the right conditions, free-radical bromination of cyclohexene can give a good yield of 3-bromocyclohexene, where bromine has substituted for an allylic hydrogen on the carbon atom next to the double bond. 

Non-functionalized alkanes are preferentially brominated at tertiary carbon atoms in preference to primary or secondary positions, with selectivity decreasing with increasing temperature. Allylic halogenation may be difficult to achieve due to competing ionic addition of Br2 across the alkene (see Section 2.2.2), but benzylic... 

The initiation step provides a radical source by thermal or photochemical dissociation of initiators, which then provides bromine radicals by reaction with Br2. Initiators are sometimes present in the alkene as allyl hydroperoxides which may be present due to inadvertent, prior autooxidation. Bromine or HBr may be present in trace amounts in NBS. Reaction of the bromine radical 20 with the substrate 1 proves selective for allylic or benzylic hydrogens due to the near thermoneutral nature of the reaction which breaks the C-H bond and forms the H-Br bond. Reaction of the formed carbon-centered radical 21 with Br2 provides the desired bromide 3 and Br 20. Hydrogen bromide 17 reacts with NBS to form succinimide 4 and resupplies the required low concentration of Br2. Alternatively, reaction of substrate radical 21 with NBS 2 provides product 3 and succinimidyl radical 22 (S ). Due to energy and kinetics considerations, abstraction of the allylic hydrogen by the S should be slower than abstraction of bromine from NBS by an allyl radical. In using solvents in which NBS, succinimide 4 or it s radical 22 are not very soluble, S is not the key chain-carrier. Byproducts and side-reactions can occur with S. ... 

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