Friedel-Crafts conjugate acids

Brmnsted-Lewis Superacids. Conjugate Friedel-Crafts acids prepared from ptotic and Lewis acids, such as HCl—AlCl and HCl—GaCl ate, indeed, supetacids with an estimated value of —15 to —16 and ate effective catalysts in hydrocarbon transformation (217). 

Carbocations formed through protonation of alkenes by proton acids are usually assumed as intermediates in alkylation with alkenes. Metal halides, when free of protic impurities, do not catalyze alkylation with alkenes except when a cocatalyst is present. It was shown that no neat conjugate Friedel-Crafts acids such as HA1C14 or HBF4 are formed from 1 1 molar compositions in the absence of excess HC1 or HF, or another proton acceptor.163-166 In the presence of a proton acceptor (alkene), however, the Lewis acid halides—hydrogen halide systems are readily able to generate carbocations ... 

Positional isomerization occurs similarly as during alkylation with alkyl halides. HF and H2S04, which are weaker catalysts than the conjugate Friedel-Crafts acids, however, do not bring about ready positional isomerization of the alkylated products. Rearrangement in the side chain always takes place before the attachment of the substituent to the aromatic ring when these catalysts are used. 

Conjugate Friedel-Crafts Acids (HBr AIBr3, HCkAICb, Etc.)... 

When alkenes are used as the alkylating agent, the catalysts are metal halides with hydrogen halide or water as cocatalyst or protic acids. Similarly, conjugate Friedel-Crafts acids such as HAICI4 or HBF4 show catalytic activity only in the presence of excess HCl or HF (eq. 59). The transformation is usually assumed to take place with the participation of carbocations formed through protonation of alkenes by proton acids. 

In a generalized sense, acids are electron pair acceptors. They include both protic (Bronsted) acids and Lewis acids such as AlCb and BF3 that have an electron-deficient central metal atom. Consequently, there is a priori no difference between Bronsted (protic) and Lewis acids. In extending the concept of superacidity to Lewis acid halides, those stronger than anhydrous aluminum chloride (the most commonly used Friedel-Crafts acid) are considered super Lewis acids. These superacidic Lewis acids include such higher-valence fluorides as antimony, arsenic, tantalum, niobium, and bismuth pentafluorides. Superacidity encompasses both very strong Bronsted and Lewis acids and their conjugate acid systems. 

Nitroalkenes are not the only substrates employed as electrophiles in these conjugate Friedel-Crafts alkylations using chiral phosphoric acids as catalysts. In fact, the first reports in this field were focused on the reaction of indoles with p,y-unsaturated ot-ketoesters as Michael acceptors, which underwent clean... 

To end this section, it has to be mentioned that there is a single example of a conjugate Friedel Crafts alkylation involving enones as Michael acceptors. In particular, a camphor-based sulfonic acid (94) has been used as catalyst in the reaction of indoles with chalcones (Scheme 4.57). It has also to be noted that the best conditions involved the use of catalyst 94 together with an ionic liquid (l-butyl-3-methyl-l//-imidazolium bromide BmimBr). However, although excellent yields were obtained for a set of different substrates tested, the enantioselectivities remained in rather low values. 

The inactivity of pure anhydrous Lewis acid haUdes in Friedel-Crafts polymerisation of olefins was first demonstrated in 1936 (203) it was found that pure, dry aluminum chloride does not react with ethylene. Subsequentiy it was shown (204) that boron ttifluoride alone does not catalyse the polymerisation of isobutylene when kept absolutely dry in a vacuum system. However, polymers form upon admission of traces of water. The active catalyst is boron ttifluoride hydrate, BF H20, ie, a conjugate protic acid H" (BF20H) . 

The most important appHcation of metal alkoxides in reactions of the Friedel-Crafts type is that of aluminum phenoxide as a catalyst in phenol alkylation (205). Phenol is sufficientiy acidic to react with aluminum with the formation of (CgH O)2Al. Aluminum phenoxide, when dissolved in phenol, greatiy increases the acidic strength. It is beheved that, similar to alkoxoacids (206) an aluminum phenoxoacid is formed, which is a strong conjugate acid of the type HAl(OCgH )4. This acid is then the catalyticaHy active species (see Alkoxides, metal). 

Alkynes are readily acylated with acid chlorides under Friedel-Crafts conditions to form, in most cases, fram-p-chlorovinyl ketones through the corresponding vinyl cation intermediate [Eq. (8.16)]. The first study in 1935 reported low yields.11 Later in acylations with acyl triflates, p-keto vinyl triflates were obtained in satisfactory yields.123 When aroyl derivatives are used, the intermediate can undergo cyclization to form indenones. Chlorovinyl ketones formed from terminal alkynes may also react further losing hydrogen chloride to yield conjugated acetylenic ketones 11,13... 

A synthesis of this compound was devised by Ohmizu, Iwasaki and co-workers and featured a three-component tandem conjugate addition/enolate trapping as key step (Scheme 12.24) [82]. In this synthesis, the acyl anion equivalent cyanohydrin 165 was first treated with LDA and allowed to react with methyl crotonate 166. The resulting enolate was trapped with 2,3,5-trimethoxy benzylbromide 168 to afford crude intermediate 169, which was immediately deprotected in situ to afford ketone product 170. Both the ester and the ketone functionalities were then reduced at low temperature to afford the corresponding diol 171. Upon treatment with trifluoroacetic acid, the desired Friedel-Craft cyclization adduct 172 was obtained. The latter tricyclic compound was then further elaborated to the final target 164 through a short sequence of standard transformations. 

Aromatic compounds are good enough nucleophiles to add in conjugate fashion under Friedel-Crafts conditions so that no organo-metallic reagent is needed. Benzene adds to cinnamic acid 74 with AICI3 as catalyst to give 73 in one step.17... 

Electrophilic substitution of nitro and sulfonic acid groups occurs in strongly acid media and involves attack on the conjugate acid of imidazole—a system exhibiting pronounced deactivation. Electron density calculations294,296 297 predict the experimentally found substitution at positions 4 and 5. Acylation under Friedel-Crafts conditions does not occur in imidazoles. 

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