Halides, aryl, arylation Friedel-Crafts alkylation

Despite its utility, the Friedel-Crafts alkylation has several limitations. For one thing, only alkyl halides can be used. Aromatic (atyl) halides and vinylic halides do not react because aryl and vinylic carbocations are too high in energy to form under Friedel-Crafts conditions. 

To be really satisfactory, a Friedel-Crafts alkylation requires one relatively stable secondary or tertiary carbocation to be formed from the alkyl halide by interaction with the Lewis acid, i.e. cases where there is not going to be any chance of rearrangement. Note also that we are unable to generate carboca-tions from an aryl halide - aryl cations (also vinyl cations, see Section 8.1.3) are unfavourable - so that we cannot nse the Friedel-Crafts reaction to join aromatic gronps. There is also one further difficulty, as we shall see below. This is the fact that introduction of an alkyl substitnent on to an aromatic ring activates the ring towards fnrther electrophilic substitution. The result is that the initial product from Friedel-Crafts alkylations is more reactive than the... 

C-Alkylations have been performed with both support-bound carbon nucleophiles and support-bound carbon electrophiles. Benzyl, allyl, and aryl halides or triflates have generally been used as the carbon electrophiles. Suitable carbon nucleophiles are boranes, organozinc and organomagnesium compounds. C-Alkylations have also been accomplished by the addition of radicals to alkenes. Polystyrene can also be alkylated under harsh conditions, e.g. by Friedel-Crafts alkylation [11-16] in the presence of strong acids. This type of reaction is incompatible with most linkers and is generally only suitable for the preparation of functionalized supports. Few examples have been reported of the preparation of alkanes by C-C bond formation on solid phase, and general methodologies for such preparations are still scarce. 

Vinyl halides and aryl halides do not react in Friedel-Crafts alkylation. 

Most Friedel-Crafts reactions involve carbocation electrophiles. Because the carbocations derived from vinyl halides and aryl halides are highly unstable and do not readily form, these organic halides do not undergo Friedel-Crafts alkylation. 

We have encountered three limitations to the use of Friedel-Crafts alkylation (a) the danger of polysubstitution (b) the possibility that the alkyl group will rearrange and (c) the fact that aryl halides cannot take the place of alkyl halides. Besides these, there are several other limitations. 

It is typical of aryl halides that they undergo nucleophilic substitution only with extreme difficulty. Except for certain industrial processes where very severe conditions are feasible, one does not ordinarily prepare phenols (ArOH). ethers (ArOR), amines (ArNH2), or nitriles (ArCN) by nucleophilic attack on aryl halides. We cannot use aryl halides as we use alkyl halides in the Friedel-Crafts reaction. 

Halogen atoms on sp hybridized carbons (vinylic and aryl halides) do not react to produce electrophiles under conditions of the Friedel-Crafts alkylation because... 

In 1877, Charles Friedel and James Mason Crafts [30a, b] corporately discovered that treatment of amyl chloride with aluminum strips in benzene led to the formation of amylben-zene. This type of transformation was found to be general for alkyl halides and aromatics under the catalysis of Lewis acid. Along with the discovery of the closely related acylation [30c, d], these two men are best remembered by Friedel-Crafts reaction that bears their names. With various modem modifications that appeared in the Uterature, including enan-tioselective variants [31], Friedel-Crafts alkylation and acylation have already become one of the most powerful C—C bond forming reactions in organic chemistry [32]. These methods are recognized to date as of fundamental importance not only in acadania but also in industry [33]. As shown in Scheme 10.18, some heteroaromatics, instead of the aryl component or alcohol, and alkenes instead of halides can be used as suitable substrates. Also, other common Lewis acids like BFj, TiCl, SnCl, ScfOTOj, etc., and Brpnsted acids snch as HF, H SO, and superacids (e.g., HF SbFj, HS03-SbFj) can also used as catalysts. 

Another version of the Friedel-Crafts reaction uses acyl halides instead of alkyl halides and yields aryl ketones... 

Vinylic halides and aryl halides do not form carbocations under conditions of the Friedel-Crafts reaction and so cannot be used in place of an alkyl halide or an acyl halide... 

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