Allylic bromide, from alkenes

Preparation of allylic bromides from alkenes (Section 12.2)... 

Diterpenoids related to lambertianic acid were prepared by intramolecular cyclization of either an alkene or an alkyne with a furan ring <2005RJ01145>. On heating amine 101 with allyl bromide, the intermediate ammonium ion 102 was formed which then underwent [4+2] cycloadditions in situ to give the spiroazonium bromides 103 and 104 (Scheme 13). These isomers arose from either endo- or co-transition states. The analogous reaction was also carried out with the same amine 101 and propargyl bromide. The products 105 and 106 contain an additional double bond and were isolated in 58% yield. The product ratios of 103 104 and 105 106 were not presented. 

In 1975, van der Baan and Bickelhaupt reported the synthesis of imide 37 from pyridone 34 as an approach to the hetisine alkaloids, using an intramolecular alkylation as the key step (Scheme 1.3) [23]. Beginning with pyridone 34, alkylation with sodium hydride/allyl bromide followed by a thermal [3,3] Claisen rearrangement gave alkene 35. Next, formation of the bromohydrin with A -bi omosuccinimide and subsequent protection of the resulting alcohol as the tetrahydropyranyl (THP) ether produced bromide 36, which was then cyclized in an intramolecular fashion to give tricylic 37. 

Allylic bromination normally uses NBS as bromine itself would add to the alkene. Thus cyclohexene gives the dibromide 18 with Br2 but the allylic bromide with NBS. Bromine radicals abstract one of the marked H atoms from 19 and the intermediate allylic radical 21 is delocalised so we don t know which end of the allylic system5 ends up attached to Br. 

The reaction of 83 with NaH and allyl bromide afforded 86. In this product, the double bonds are distant from the ring by a CH2 group, so 86 underwent a typical alkene reaction, for example bromination, affording 87 (Scheme 9) <1996CB161>. 

An allyl radical can be brominated at both termini of the radical. This is why two allyl bromides can result from the Wohl-Ziegler bromination of an alkene if the allyl radical intermediate is unsymmetrical (examples see Figures 1.29-1.31). Even more than two allyl bromides may form. This happens if the substrate possesses constitutionally different allylic H atoms, and if, as a result thereof, several constitutionally isomeric allyl radicals form and react with bromine without selectivity. 

We shall finish this chapter with some alkenes that are electrophilic, not because they are conjugated with another n system, but because they have a leaving group adjacent to them. We shall start with some substitution reactions with which you are familiar from Chapter 17. There we said that allyl bromide is about 100 times more reactive towards simple S>j2 reactions than is propyl bromide or other saturated alkyl halides. 

The transfer of electrons is not susceptible to steric hindrance so substituted alkenes pose no problem. In the next example, the enolate reacts with allyl bromide to give a single stereoisomer of the product (the allyl bromide attacks from the face opposite the methyl group). Naturally, only one regioisomer is formed as well, and it would be a tall order to expect formation of this single enolate regioisomer by any form of deprotonation method. 

In both cases we must consider the danger of enolate formation from the ketone. In the first case the alcohol might displace the bromide or attack the ketone and in the second the allylic bromide might be attacked at the alkene though this makes no difference as the allylic system is symmetrical. The first approach is easier as the bromoketone is easily made from acetone (Chapter 21) and the allylic halide in the second approach would probably be made from the alcohol used in the firs synthesis. 

The reactivity of alkenes toward dichlorocarbene also decreases if there is a halogen in an allylic position. In this case side reactions, such as alkylation of trichloromethyl anion, halide exchange in the case of allylic bromides etc., take place. Although the yields of the products from these side reactions are low, they impede the isolation of the desired product, e.g. formation of 3, 4, and... 

The reaction of dibromocarbene with haloalkenes (vinyl halides, alkenes with a halogen more distant from the double bond) leads to the formation of 1,1-dibromocyclopropanes in poor to good yields. However, reactions with allyl halides, particularly substituted allyl bromides, require comment. These alkenes furnish, apart from 1,1-dibromocyclopropanes 1, the alkylation products of tribromomethyl anion 2 and, occasionally, the products of their further transformations (dibromocarbene adducts 3, products of elimination of hydrogen bromide 4 etc.) if they react with bromoform under phase-transfer catalysis conditions (Houben-Weyl, Vol.E19b, pi620). 

In practice 136 was not made from proline. Breaking open the other, more functionalised, ring 136a is possible with the idea of a radical cyclisation onto an alkene 137. FGI of hydroxyl for iodine reveals the elements of another amino acid, serine 140 and an allylic bromide 139. 

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. 

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