Lewis acid catalysis Friedel-Crafts alkylation

Beside the Friedel-Crafts-type alkylation of arenes, the direct functionalization of 2,4-pentanediones is of great interest in Lewis acid catalysis. Although Pd-catalyzed Tsuji-Trost type allylations of 1,3-diketones are known, direct benzylation procedures catalyzed by Lewis acids are less explored [40-43]. Based on the previously described Friedel-Crafts alkylation of arenes and heteroarenes, the Rueping group developed a Bi(OTf)3-catalyzed benzylation of 2,4-pentanediones. Alcohols such as benzyl, allyl or cinnamyl alcohols were used as the electrophilic component to yield important 2-alkylated 1,3-dicarbonyl compounds. Initially, different Bi(III) salts were screened. In contrast... 

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. 

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. 

Examples here are Friedel-Crafts alkylations and acylations, in which the zeolite catalyst replaces the homogeneous Lewis acid. Zeolite catalysts can also be used in place of mineral acids and organic acids. However, these catalyst substitutions also involve changing the process from homogeneous to heterogeneous catalysis. 

As already noted in Scheme 8.24, substitution of hydrogen by an alkyl group can also be effected. Generally, such Friedel-Crafts alkylations with phenols require catalysis by Lewis acids just as they did with unsubstituted and alkyl-substituted arenes (Chapter 6). Despite the fact that the nonbonded electrons on the hydroxyl... 

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. 

As an example involving Lewis acid-base catalysis, we can cite the case of Friedel-Crafts alkylation of benzene hydrocarbons catalyzed by aluminum chloride, which is a Lewis acid. A four-step mechanism reports the results ... 

There is one type of Lewis acid catalysis with which we should be very familiar—a range of Lewis acids such as AICI3, SnCl, and FeClj catalyze the Friedel-Crafts alkylation and acylation of aromatic compounds (Figure 23.6 see Section 12.2.2). 

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. 

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. 

Carboxylic acid anhydrides or halides normally require the presence of a Lewis acid (often boron trifluoride) for Friedel-Crafts acylation of furans, though trifluoroacetic anhydride will react alone. Aluminium-chloride-catalysed acetylation of furan proceeds 7 x lO times faster at the a-position than at the P-position. 3-Alkyl-furans substitute mainly at C-2 2,5-dialkyl-furans can be acylated at a P-position, but generally with more difficulty. 3-Bromofuran is efficiently acetylated at C-2 using aluminium chloride catalysis. ... 

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