Alkenes radical bromination

The next key intermediate is a diene, which is reached by an overall oxidation of the iodide protection of nitrogen and elimination of the iodide gives the only possible alkene. Radical bromination with NBS followed by treatment with base in ethanol both hydrolyses the lactam and eliminates bromide to give the diene. 

The intramolecular reaction of activated alkenes of the type 8 leads to the formation of 5- or 6-membered rings [26] and has been carried out only at a mercury cathode in a divided cell. In these processes, the activated alkene radical-anion is formed at a less negative potential than that required for cleavage of the carbon-bromine bond. Cyclization then occurs by nucleophilic substitution. 

Novel results were reported for allylic bromination. In radical bromination of cyclohexene in CCI4 under light the selectivity of substitution over addition was shown to be controlled by bromine concentration.304 Substitution via the corresponding allyl radical, while relatively slow, is irreversible and fast enough to maintain the concentration of bromine at a sufficiently low level to prevent significant addition. The reaction of two strained alkenes, fZ)-1,2-dimethyl-1,2-di-ferf-butylethylene and the -isomer (14), leads to the corresponding bromosubstituted product, instead of addition 305... 

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. 

The amide N-H may also be halogenated, oxidized and nitrosated. A -Bromosuccinimide (NBS), like a number of other iV-halo compounds, readily undergoes a radical fission to give a bromine radical. This provides a useful reagent for radical bromination at, for example, allylic or benzylic positions. In the presence of acid, NBS is also a mild source of the halonium ion, which is used for the addition of hypobromous acid (Scheme 3.74) to alkenes or for the bromination of reactive aromatic rings. 

BMI. Radical bromination to give (9) (eq 3), Arbuzov reaction, and alkenation lead to ( )-5-alkylidene-Boc-BMI, to which cuprates add highly diastereoselectively with formation of the imidazolidinones (10) containing two new stereogenic centers (eq4). ... 

Alkenes undergo radical halogenation at the allylic positions. NBS is used for radical bromination at the allylic position (Section 9.5). 

Because radical brominations are so selective, they can be used successfully in the laboratory to make alkyl bromides. There are relatively few ways of functionalizing an unfunctionalized centre, and radical allylic bromination is one of the most effective. We introduced this reaction in Chapter 24, where we contrasted the radical reactivity of Bt2 towards alkenes (leading to an allyl bromide by hydrogen abstraction) with its ionic reactivity (leading to addition of bromine across the alkene). We can now look in a little more detail at the selectivities involved. 

If the mechanism is different (suggested by formation of a different product), then some chemical process must occur before HBr can react with the alkene. Logically, this event involves the new additive, the peroxide, which is known to undergo homolytic bond fragmentation to produce radicals. If radicals are involved, does the bromine go in first or second If a secondary radical is assumed to be more stable than a primary radical (as with carbocations, which are electron deficient), the most reasonable mechanism generates a bromine radical (Br ), which reacts with the C=C unit of the alkene. The bromine must add to the C=C unit before the H in order to generate a secondary radical, and this will place bromine on the less substituted carbon. 

Until now, we have focused on reactions of alkanes. Now let s consider the radical halogenation of alkenes. For example, consider what outcome you might expect when cyclohexene undergoes radical bromination. Begin by comparing all C—H bonds to identify the bond that is most easily broken. Specifically, compare the BDE for each type of C—H bond in cyclohexene. 

This alkene can be made from the starting alkane in two steps (radical bromination, followed by elimination), giving the following synthesis ... 

Now let s draw the forward scheme. Radical bromination of the starting cycloalkane gives a tertiary alkyl bromide, which is then converted into an alkene upon treatment with a strong base, such as ethoxide. Ozonolysis causes cleavage of the C=C bond, thereby opening the ring and giving a dicarbonyl compoimd, which can then be converted into the product via reductive amination, upon treatment with excess dimethylamine and sodium cyanoborohydride with acid catalysis. 

The forward scheme is shown here. Methylcyclopentane will undergo radical bromination selectively at the tertiary position, giving a tertiary alkyl bromide. This aUcyl bromide will undergo an elimination reaction upon treatment with a strong base, such as sodium ethoxide. Ozonolysis of the resulting alkene gives a dicarbonyl compound, which can then be converted into the product upon treatment with methyl amine and sodium cyanoborohydride (with acid catalysis) ... 

The regioselectivity of addition of HBr to alkenes under normal (electrophilic addi tion) conditions is controlled by the tendency of a proton to add to the double bond so as to produce the more stable carbocatwn Under free radical conditions the regioselec tivity IS governed by addition of a bromine atom to give the more stable alkyl radical Free radical addition of hydrogen bromide to the double bond can also be initiated photochemically either with or without added peroxides... 

N Bromosuccimmide provides a low concentration of molecular bromine which reacts with alkenes by a mechanism analogous to that of other free radical halogenations... 

The stereoselectivity of the radical addition can be explained in terms of a bridged structure similar to that involved in discussion of ionic bromination of alkenes ... 

---