Lewis acid catalysis Friedel-Crafts reaction

Within the last few years, it has conclusively been demonstrated that the Diels-Alder reaction is susceptible to catalysis with Lewis acids or Friedel-Crafts catalysts such as aluminum chloride (15, 18, 36, 37, 38, 39, 40, 57, 67, 68, 69, 70, 71, 82, 86). As a result of catalysis, it was possible to change the following ... 

It turned out that the Friedel-Crafts reaction and the chlorination can be done in the same pot. The vhlorination needs to be chemoselective as reaction on -.he methyl group or next to the carbonyl group could ccur. Lewis acid catalysis Is the answer. 

Many important reactions involve catalysis by Lewis acids or bases. One of the most important of these is the type of reaction carried out by Charles Friedel and James Crafts. These reactions, known as the Friedel-Crafts reactions, actually involve several types of important processes. One of these is alkylation, which is illustrated by the reaction of benzene with an alkyl halide in the presence of A1C13, a strong Lewis acid. 

Another advantage of this approach is that we can now use electrophilic substitution on the pyrrole to add the rest of the molecule. So the secondary benzylic alcohol 106 might well cyclise to 105 with Lewis acid catalysis as the cation will be reasonably stable and the reaction is intramolecular. But the Friedel-Crafts alkylation to give 107 will not succeed as the cation would be primary. 

A more important variation is the Friedel-Crafts acylation with acid chlorides and AICI3. As you saw in Chapter 13, add chlorides can give the rather stable acylium ions even in hydrolytic reactions and they do so readily with Lewis acid catalysis. Attack on a benzene ring then gives an aromatic ketone. The benzene ring has been acylated. 

Scheme A brings into focus the well-known Lewis acid catalysis, of which the immediately pertinent example is the reaction of cyanogen chloride with benzene under Friedel-Crafts conditions 130-1S2) ...

Electrophiles for aromatic substitution include the halonium ion, the nitronium ion and the carbonium ion. The latter may be generated from alkyl and acyl halides using Lewis acid catalysis in the Friedel-Crafts reactions. 

One of the most important modifications of the Friedel-Crafts reaction involves the use of acid chlorides rather than alkyl halides. An acyl group, RCO—, becomes attached to the aromatic ring, thus forming a ketone the process is called acylation. As usual for the Friedel-Crafts reaction (Sec. 12.8), the aromatic ring undergoing substitution must be at least as reactive as that of a halobenzene catalysis by aluminum chloride or another Lewis acid is required. 

Many catalysts are only required in trace amounts in order to affect the rate of the reaction. Some, however, are required in similar quantities to the reagents, in which case they are called stoichiometric catalysts. This often indicates that the catalyst is forming a complex with one of the reagents, and it is this complex that is the attacking species in the reaction. An example of this is the Lewis acid catalysis of the Friedel-Crafts reaction. 

The application of the aliphatic Friedel-Crafts reaction (chapter 5) to alkynes is a stereoselective approach to vinyl-lithiums that forms a bridge between the Shapiro reaction and the next section-hydrometallation. Acid chlorides 64 react with alkynes under Lewis acid catalysis to give E-P-chloroenones -65 stereoselectively. The chlorine can be replaced by more reactive iodine by conjugate substitution.11... 

If the electrophile also benefits from Lewis acid catalysis, as in the aliphatic Friedel-Crafts reaction, good yields of products are generally found. The anion of the allyl phosphonate 192 can be silylated to give the vinyl silane 193 and this reacts in turn with the classical combination of acetyl chloride and A1C13 to give the enone -194 that can be used in HWE reactions to make dienones46 (chapter 15). 

During recent years, asymmetric catalysis by small organic molecules has received much attention [140]. Because these reactions proceed through intermediates that are inherently less reactive, the Friedel-Crafts reactions of electron-rich (hetero)aryls generally seem to be well suited. For instance, Deng described the use of readily accessible cinchona-derived ligand 178 to perform highly enantioselective indole additions to a-ketoesters and even simple aldehydes (Scheme 8.49) [141]. Bisindole adducts, the major side products in many Lewis acid-catalyzed reactions, were formed to only a minor extent. 

In the case of Friedel-Crafts reactions which produce hydrogen chloride as a side product, catalysis is a misnomer. Although on paper the reaction may be written as a catalytic cycle (Figure 16.10), in practice the hydrogen chloride may fail to dissociate from the Lewis acid centre. Consequently stoichiometric quantities of aluminium trichloride may be required. 

Friedel-Catalysts n Strongly acidic metal halides such as aluminum chloride, aluminum bromide, boron trifluoride, ferric chloride, and zinc chloride, used in the polymerization of unsaturated hydrocarbons, e.g., olefins. (Friedel-Crafts reactions using such catalysis are named for Charles Friedel and James Crafts, who first used them in 1877.) These acidic halides are also known as Lewis acids. 

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. 

For example, Friedel-Crafts reactions are catalyzed by Lewis acids (AICI3, BF3, etc.). The catalysis only acts during the initiation stage ... 

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