Alkenes allylic halogenation

The fact that the bromine concentration remains at veiy low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must... 

Naphthalene dioxygenase from P. putida strain FI is able to oxidize a number of haloge-nated ethenes, propenes, and butenes, and d5 -hept-2-ene and cis-oct-2-ene (Lange and Wackett 1997). Alkenes with halogen and methyl substituents at double bonds form allyl alcohols, whereas those with only alkyl or chloromethyl groups form diols. 

Sequential cross-coupling can be used also for synthesis of 1,1-disubstituted alkenes from 2,3-dibromopropene (Aldrich). The allylic halogen couples directly with a Grignard reagent vinylic coupling is slower and requires a catalyst (equation I). 

Conceptually similar a,a -annulations of ketone enamines have also been carried out with electrophilic alkenes containing a reactive allylic halogen, such as ethyl a-bromo-methylacrylate or dimethyl y-bromomesaconate318-320 (Scheme 156). An elegant one-pot synthesis of the adamantane ring system involving sequential double Stork and Dieckmann reactions has been developed by Stetter and Thomas321 (Scheme 157). Reaction of the bis-enamine 154 with ethyl a-bromomethylacrylate leads to the pentacy-clic system 155322 (Scheme 158). 

Problem 15.24 Which compounds can be prepared in good yield by allylic halogenation of an alkene ... 

PROBLEM 10.5 The two alkenes 2,3,3-trimethyl-1-butene and 1-octene were each subjected to allylic halogenation with A/-bromosuccinimide. One of these alkenes yielded a single allylic bromide, whereas the other gave a mixture of two constitutionally isomeric allylic bromides. Match the chemical behavior to the correct alkene and give the structure of the allylic bromide(s) formed from each. 

The alkene, allyl, and alkyne complexes of Pd and Pt have been discussed to a large extent in earlier Sections, as have the use of palladium species in catalysis (Chapters 23 and 24). Here we deal mainly with complexes of the type MXHL2 and MXRL2 where X is halogen, R is an alkyl or aryl group and L is usually a tertiary phosphine. 

The fact that the Br2 concentration remains at very low levels is important to the success of the allylic halogenation process. The allylic bromination of alkenes must compete with polar addition of bromine via a bromonium ion intermediate. The reactions differ in their dependence on bromine concentration. The allylic substitution is one-half order in bromine, whereas the addition reaction follows a first- or second-order dependence on [Br2] (see Section 5.3). Therefore a low concentration of Br2 favors substitution over addition. 

Physical Properties of Haloalkanes Preparation of Haloalkanes by Halogenation of Alkanes Mechanism of Halogenation of Alkanes Allylic Halogenation Radical Autoxidation Radical Addition of HBr to Alkenes... 

Both alkyl and alkenyl amino acids can be prepared by this approach. A common method for introducing the halide into an alkene-bearing molecule is illustrated by the reaction of -pent-2-enoic acid with N-bromosuccinimide to form 1.12. Subsequent treatment with ammonia led to displacement of the bromine moiety to give 4-aminopent-2-enoic acid (J.I3). An alternative method reacted 1.12 with sodium azide and then reduced the azide with zinc and acetic acid (see section l.l.B.iv). Allylic halogenation in systems such as 1.12 are well known. 

There are some instances where the chlorination or bromination reaction can be used to good effect, however. Alkenes that have allylic hydrogens can sometimes be halogenated specifically at an allylic position in a process called allylic halogenation, another free radical chain reaction. For example, when low concentrations of bromine are photolyzed in the presence of the complicated cyclohexene shown in Figure 11.51, the product is exclusively brominated in one allylic position. 

PROBLEM 11.49 Predict the major product(s) for the reaction between NBS (allylic halogenation) and the following alkenes ... 

The greater stability of allylic radicals relative to their alkyl counterparts suggests that free-radical halogenation of alkenes should be both feasible and regioselective for the allylic position. Although, as we have already seen, the typical reaction of alkenes with halogens at room temperature and below is electrophilic addition 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... 

In Summary Under radical conditions, alkenes containing allylic hydrogens enter into allylic halogenation. A particularly good reagent for allylic bromination is A-bromobutanimide (A-bromosuccinimide, NBS). 

The catalysis by Yb(OTf)3-Me3SiCl is quite useful for allylic halogenation of 1,1-disubstituted alkenes with NBS, NCS and NIS [157]. In contrast to the conventional method using a radical initiator, this method does not cause benzylic halogenation. Thus, the reaction of l-isopropenyl-2-methylbenzene with NBS and NCS gives allyl halides in good yield without benzylic halogenation (Scheme 9.66). 

Although alkenes typically react with chlorine and bromine by addition at room tern perature and below (Section 6 14) substitution becomes competitive at higher tempera tures especially when the concentration of the halogen is low When substitution does occur It IS highly selective for the allylic position This forms the basis of an industrial preparation of allyl chloride... 

This allylic bromination with NBS is analogous to the alkane halogenation reaction discussed in the previous section and occurs by a radical chain reaction pathway. As in alkane halogenation, Br- radical abstracts an allylic hydrogen atom of the alkene, thereby forming an allylic radical plus HBr. This allylic radical then reacts with Br2 to yield the product and a Br- radical, which cycles back... 

Simple alkyl halides can be prepared by radical halogenation of alkanes, but mixtures of products usually result. The reactivity order of alkanes toward halogenation is identical to the stability order of radicals R3C- > R2CH- > RCH2-. Alkyl halides can also be prepared from alkenes by reaction with /V-bromo-succinimide (NBS) to give the product of allylic bromination. The NBS bromi-nation of alkenes takes place through an intermediate allylic radical, which is stabilized by resonance. 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

The radical addition of halogen to an alkene has been referred to briefly in Section 9.3.2. We saw an example of bromination of the double bond in cyclohexene as an unwanted side-reaction in some allylic substitution reactions. The mechanism is quite straightforward, and follows a sequence we should now be able to predict. 

Radical addition of HBr to an alkene depends upon the bromine atom adding in the first step so that the more stable radical is formed. If we extend this principle to a conjugated diene, e.g. buta-1,3-diene, we can see that the preferred secondary radical will be produced if halogenation occurs on the terminal carbon atom. However, this new radical is also an allylic radical, and an alternative resonance form may be written. 

---