Allylic carbon halogenation

Yanagisawa, A., Habaue, S., Yamamoto, H. Direct insertion of alkali (alkaline earth) metals into allylic carbon-halogen bonds avoiding stereorandomization. J. Am. Chem. Soc. 1991,113, 5893-5895. 

Another important mechanism for the allylic carbon-halogen bond cleavage involves prior r/ -coordinafion of the C=C double bond to the transition metal followed by Sn2- or SN2 -type nucleophilic addition (Scheme 3.8). 

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

Similar reactions occur with all aliphatic halides and the rates of substitution are related to the degree of ionic character of the carbon-halogen bond. For preparation purposes, trityl bromide or propargyl bromide are more convenient than allyl bromide. The compounds obtained are listed in Table XI. They were obtained pure and characterized fully. Zr (allyl) 3Br and Zr(allyl)2Br2 are sufficiently soluble in toluene for polymerizations to be initially homogeneous. Their relative reactivities are listed in Table XI. In all cases hydrogen was used to reduce the molecular weight of the polymer formed. In this respect the polymer derived from Zr (allyl )3Br was more readily modified than that from Zr (allyl) 4, but in order to avoid... 

These are the compounds in which the halogen atom Is bonded to an sp -hybridlsed carbon atom next to carbon-carbon double bond (C=C) i.e. to an allylic carbon. 

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. 

When designing substances that contain oleftnic or acetylenic moieties, chemists should keep in mind the potential for these substituents to be bioactivated to electrophilic species and, whenever possible, incorporate other structural changes that lessen the likelihood for bioactivation. Terminal carbon-carbon double or triple bonds should be avoided or at least contain an alkyl substituent on the C-2 carbon (in the case of olefins) and alkyl substituents on the allylic or propargylic carbons. Halogens on terminal unsaturated carbons should be avoided. Aromatic substituents at the allylic or propargylic positions should also be avoided if allylic or propargylic hydrogens are present. 

Halogen compounds in which the carbon-halogen bond is adjacent to a double bond, as in C=C—C—X are known as allylic halides. The simplest example is 3-chloropropene, CH2=CHCH2C1, which is made on a large scale by the radical chlorination of propene at 400° ... 

The carbon-halogen bonds of allylic halides are especially reactive in both SN1 and Sn2 reactions (Table 14-6). The reasons for the enhanced SN1 reactivity have been discussed previously (Section 8-7B). For example, the ease... 

The silver ion assisted carbon-halogen bond cleavage and the unraveling of the cyclopropane ring by the cyclopropyl-allyl rearrangement was first noted in the formation of 2-bromocyclohexen-l-ol from dibromobicyclo[3.l.0]hexane under solvolytic conditions (equation 86).220 The silver ion assisted solvolysis of the dihalocyclopropane adduct (43), derived from a Birch reduction product, smoothly rearranges to the tropone (equation 87).221 A number of other synthetic applications222-226 have beien reported... 

Since a carbon-halogen bond is more easily reduced than a silicon-halogen bond, cathodic reduction of organic halides such as allyl, benzyl, aryl and vinyl halides in the... 

Greater sensitivity is obtained if the halogen atom is attached to an allyl carbon atom than the corresponding saturated compound. 

Support for the proposal of M+ insertion into the carbon-halogen bond came from later work in which the reactivity of the Fe(CO) + ions (n = 0 - 5) towards allyl chloride was investigated using a MS/MS/MS multiquadrupole spectrometer60. Thus, while with the naked Fe+ the only observed products were FeCl+ (minor) and C3H5+ (and the secondary products derived from its reaction with neutral allyl chloride), with the iron carbonyl... 

Scheme 1 depicts some of the outcomes possible (5) when a metal atom reacts with an organic molecule, which might be a monomer or a substituent on a polymer. Some of the more common reactions are generalized. Oxidative addition is relevant to insertion of a metal atom into a carbon-halogen bond, such as might be found in polyvinyl chloride or the monomer, allyl chloride, or... 

Heme haloperoxidases can also use peroxide and halide ions to halogenate an activated (benzylic/allylic) carbon. The halide is first oxidized to an active halogenating intermediate (Fig. 10.4, pathway (2)). The substrate is halogenated in the next step. The overall reaction is... 

The discussion above emphasizes that the allyl-Ni reagents are quite selective for carbon halogen bonds, especially allyl, vinyl, and aryl halides. At the same time, modest reactivity as nucleophiles toward reactive carbonyl derivatives has been reported.Simple aldehydes, the more reactive ketones (such as cyclopentanone and benzoquinone), and certain epoxides will undergo 1,2-addition of the aUyl ligand to the carbonyl group. Esters, amides, and, most remarkably, acyl halides are inert toward the allyl Ni reagents under conditions where the reagents do not decompose thermally (<80 °C or so). 

Because allylic C—H bonds are weaker than other sp hybridized C-H bonds, the allylic carbon can be selectively halogenated by using iV-bromosuccinimide (NBS, Section 10.15) in the presence of light or peroxides. Under these conditions only the allylic C-H bond in cyclohexene reacts to form an allylic halide. 

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. 

Radical halogenation of alkanes was discussed in Chapter 15. The mechanism of radical halogenation at an allylic carbon was given in Section 15.10. 

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