Friedel-Crafts reaction cocatalysts

Anhydrous Lewis acids themselves are suitable catalysts for Friedel-Crafts reactions of compounds containing n-donor groups. However, they are generally insufficient as acceptors in reactions of alkenes or alkynes or isomerization of hydrocarbons. These reactions generally require a cocatalyst, such as a hydrogen halide or other cationic species. 

The cationic polymerization of several para-substi-tuted a-methylstyrenes initiated by various Friedel-Crafts catalyst-cocatalyst combinations has been studied for the effects of catalyst type, monomer substituent and reaction solvent polarity on polymer structure and properties. By using solvent mixtures, the tacticity of the resulting polymers could be varied over a wide range, the syndiotactic form being favored in the more polar mixtures. 

In 2008, Chi et al. reported a tandem reaction of indoles, a,P-unsaturated aldehydes, and methyl vinyl ketone (MVK) for the synthesis of chiral indole derivatives with two stereogenic centers [ 19]. To avoid the interference of the two secondary amine catalysts and cocatalyst acid, the soluble star polymer-based site isolatbn method was adopted, whereby the supported imidazolidinone catalyst promoted initial Friedel-Crafts alkylation and the supported pyrrolidine derivative promoted the following Michael addition to MVK (Scheme 9.19). Notably, simple combination of these catalysts in one pot didn t mediate the cascade reaction efficiently despite the fact that the MacMillan imidazolidinone and pyrrolidine catalyst can efficiently promote separate Friedel-Crafts reaction and Michael addition, respectively. Moreover, when the pyrrolidine catalyst was replaced by its enantiomer, a diaste-reomer of the product could be obtained with high enantioselectivity. This smdy presented a novel solution to the efficient combination of incompatible substrates and catalysts. 

The three-component synthesis of benzo and naphthofuran-2(3H)-ones from the corresponding aromatic alcohol (phenols or naphthols) with aldehydes and CO (5 bar) can be performed under palladium catalysis (Scheme 16) [59,60]. The mechanism involves consecutive Friedel-Crafts-type aromatic alkylation and carbonylation of an intermediate benzylpalla-dium species. The presence of acidic cocatalysts such as TFA and electron-donating substituents in ortho-position (no reaction with benzyl alcohol ) proved beneficial for both reaction steps. 

Under similar oxidative conditions, with activation of the aromatic C-H bond, some arenes could be used directly as aryl sources [41]. Unfortunately, by analogy with the Friedel-Crafts acylation, this reaction is regioselective for very few substrates only. High regioselectivity was, however, obtained if coordinating substituents on the arenes facilitate an orthopalladation reaction by a Pd(II) species [42]. After carbometallation and reductive elimination, Pd(0) is released, which has to be converted into the initial Pd(II) species in an extra oxidation step. Usually, quinines are used for this purpose, but in combination with certain heteropolyacids as cocatalysts even molecular oxygen can be employed as the oxidant. 

Thus it appears that carbonium ion reactions of the Friedel-Crafts type can only proceed in ternary or three component systems, i.e., in the presence of a suitable third component commonly called the cocatalyst. Consequently, it must be assumed that either the Bronsted acid or the Lewis acid forms a primary complex with the substrate — otherwise carbonium ion reactions would become termolecular which is extremely unlikely (58). Apparently the active ion pair is formed by either a bimolec-ular reaction between "primary complexes and the third component (a, b and c) or by a unimolecular rearrangement from a ternary complex... 

The polymerisation of benzene through repeated nucleophilic substitutions on the rings was studied by Kovacic et al. using ferric chloride as catalyst and water as cocatalyst. This system is of course outeide the realm of cationic polymerisation throu the double bcmd of an olefin, but illustrates well the role of water in Friedel-Crafts polycondensations. The authors showed that the rate of this reaction went throu a maximum at a catalyst/cocatalyst ratio of one and attributed this observation to the high activity of ferric chloride monohydrate ... 

Polymer Tacticity. Our initial results on the polymerization of several different p-substituted-a-methylstyrene monomers indicated that there was some relationship between polymer stereoregularity and both the type of initiator and substituent in these monomers ( ). However, our recent investigations with a much wider variety of monomers, catalysts and cocatalysts revealed that the classical approach to analyzing substituent effects in organic reactions, the use of the Hammett pa relationship, gave no simple and self-consistent relationship between tacticity and the a (or a ) constant for the para-substituent. These results are summarized in the data in Table I for the cationic polymerization of a-methylstyrene and a series of five p-substituted-a-methylstyrene monomers initiated with two different Friedel-Crafts catalysts, TiCl and SnCl, either alone or with a cocatalyst benzyl chloride (BC) or t-butyl chloride (TBC), in methylene chloride at -78°C. Where a cocatalyst was used, the initiator was presumably a carbonium ion formed by the following reaction ... 

It is apparent to the authors that the presence in a catalyst of a strong Brpnsted acid as such is not a required intermediate for carbonium-ion formation. It is only necessary that the catalyst has the ability to form stable carbonium ions. In reactions involving Friedel-Crafts catalysts, the aluminum halides and boron trifluoride do not form stable Brpnsted acids but they do form stable carbonium ions in the presence of certain cocatalysts and substrates. The formation of carbonium ions from ole-... 

Friedel-Crafts Acylation, Alkylation, and Related Reactions. While a stoichiometric amount of AICI3 is needed in Friedel-Crafts acylations, a small amount of Sc(OTf)3 smoothly catalyzes the same reaction. In the acetylation of thioanisole and o- or m-dimethoxybenzene, a single acetylated product is formed in an excellent yield. In the benzoylation of anisole, both benzoic anhydride and benzoyl chloride are effective, while benzoic anhydride gives a slightly higher yield. Addition of lithium perchlorate (LiC104) as a cocatalyst improves the yield dramatically (eq 13). ... 

Furans represent an important class of electron-rich heterocycles which are useful intermediates in synthetic chemistry and are broadly found as structural motifs of many natural products and pharmaceutically important substances [333]. Since furans are generally less nucleophilic than indoles and pyrroles, their catalytic enantioselective Friedel-Crafts-type conjugate addition has been much less developed so far. Very recently Harada et al. have developed a catalytic system able to achieve good enantioselectivities in the Friedel-Crafts alkylation of electron-rich furans with acychc a,p-unsaturated ketones [334]. As depicted in Scheme 2.117, a//o-threonine-derived oxazaborolidinone 190 (10 mol%) in the presence of V,V-dimethyl benzylamine (10 mol%) as cocatalyst in ether at -40°C, is an efficient catalytic system for the reaction affording the corresponding functionalized furans with good yields and enantioselectivities. 

The use of such catalysts is justified by the fact that acidic halides (e.g., ZnCl2), which are typically Lewis acids, have little or no activity for alkylation reactions when they are used in a pure state. Nevertheless, they can be activated by the addition of low concentrations of cocatalysts (e.g., HCl) that interact with the Lewis acids generating strong Brpnsted sites [93] (note that HCl as such has a low cataljdic activity when the Friedel-Crafts alkylation is performed with alcohols). 

Cationic polymerization of unsaturated compounds proceeds through the stage of carbanion cations, called also carbocations. Typical catalysts for this reaction are strong protic acids such as sulfuric acid, perchloric and trifluoroctane or the Lewis acids, which include halides of elements III, IV and V groups of the periodic table (Friedel-Crafts catalysts), such as boron trifluoride, aluminum trichloride, tin tetrachloride and titanium tetrachloride. The activity of Friedel-Crafts catalysts increases significantly the presence of small quantities of cocatalysts, that is, ihe compounds which most often are the source of protons. 

As a result of the reaction of a Friedel-Crafts catalyst with a cocatalyst a complex compound is formed which dissociates into ions according to the scheme ... 

Pure, anhydrous Lewis acids do not catalyze the polymerization of alkenes or the Friedel-Crafts alkylation of aromatics by alkenes. Cocatalysts, such as water or a protic acid, react with the Lewis acid to produce a very strong Br0nsted acid that will pro-tonate a double bond. Therefore, use of strictly anhydrous conditions should minimize side reactions in Lewis acid-catalyzed ene, Diels-Alder, and [2 + 2] cycloaddition reactions. Unfortunately, it is difficult to prepare anhydrous, proton-free AICI3, BFj, etc. Alkylaluminum halides are easily prepared and stored in anhydrous form and, more importantly, scavenge any adventitious water, liberating an alkane and generating a new Lewis acid in the process. 

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