Friedel-Crafts type addition

During the same year, both an acid-catalyzed [60] and a TiCl4-catalyzed [61] ortho-alkylation of anilines with styrene were published, but offering only a very low selectivity. The reaction of anisole and styrene catalyzed by Mo(CO)6 [62] afforded the corresponding branched diaryl product with a comparable yield and selectivity as shown by our protocol. Furthermore, Michelet and coworkers successfully employed substituted styrenes in a gold-catalyzed tandem Friedel-Crafts-type addition-carbocyclization reaction [63]. 

Catalytic enantioselective Friedel-Crafts type addition reactions of electron-rich arenes (indoles, pyrroles etc.) with Michael acceptors have been well developed in the past years. These reactions generally are enabled by chiral Lewis acids or organocatalysts (Scheme 6.24). Chiral Lewis acid-catalyzed processes usually require bidentate substrates (chelating a,p-unsatu-rated compounds) for strong chelation activation. Monodentate compounds (simple a,p-unsaturated compounds) prove to be less selective. With chiral... 

Scheme 14.7 Catalytic asymmetric conjugate Friedel-Crafts-type addition of indoles to enones catalysed by primaiy amine Cinchona catalysts, and reaction transition state.

Whereas closely related catalysts allowed the Friedel-Crafts-type additions to be expanded to other carbonyl acceptors, such as isatins, the same reactions depicted in Schemes 14.17 and 14.18 have also been achieved in an environmentally more benign solvent, namely Solkane 365 mfc, a liquid hydrofluorocarbon (CF3CH2CF2CH3) that is nontoxic with no impact on the ozone layer, and is used as an insulating and blowing agent for polyurethane foams. To achieve useful yields and enantioselectivities in this fluorinated reaction medium, perfluorinated CPN and CPD Cinchona alkaloid derivatives, able to dissolve in it, were designed and synthesised by Shibata and coworkers (Figure 14.4). 

Scheme 1.6 Gold-catalyzed Friedel-Crafts-type addition of heteroarenes to alkynes...

Axially chiral bis-arylthiourea-based organocatalyst (6) has been developed and subjected to Friedel-Crafts type addition of indole and N-methyl pyridine to nitroalkenes (Scheme 2.31) [82]. 

Li and Wang et al. made use of 5 mol% In(OTf)3 in the Friedel-Crafts type addition of electron-rich aryl compounds to methyl trifluoropyruvate in water [48] (Figure 8.24). 

Activation of the alkyne functionality by In(III) was also implicated in the Friedel-Crafts type addition of arenes to alkynes in the study done by Shirakawa et al. [99]. Several different metal triflates were investigated and efficiencies were comparable. The authors proposed the formation of an intermediate alkenyl carbocation, instead of an In(OTf)3-alkyne complex, to account for the mandatory presence of an aryl group attached to the alkyne and the observation of both cis and trans addition products (Figure 8.49). Song and Lee et al. had found improvements in yields and reaction rates by performing the same reaction in ionic liquids, but with a clear advantage of Hf(OTf)3 over In(OTf)3 in their reaction system [100]. 

An intramolecular tpio-Friedel-Crafts-type addition of phenols to 3-alkylidene indole-nium cations and formation of iminium cations through rearomatization of the spirocy-clohexadienone units followed by an intramolecular Pictet-Spengler reaction has been reported to give tricyclic indoles (Scheme 166). ... 

Unusual cyclocarbonylation of allylic acetates proceeds in the presence of acetic anhydride and an amine to afford acetates of phenol derivatives. The cinnamyl acetate derivative 408 undergoes carbonylation and Friedel-Crafts-type cyclization to form the a-naphthyl acetate 410 under severe condi-tions[263,264]. The reaction proceeds at 140-170 under 50-70 atm of CO in the presence of acetic anhydride and Et N. Addition of acetic anhydride is essential for the cyclization. The key step seems to be the Friedel-Crafts-type cyclization of an acylpalladium complex as shown by 409. When MeOH is added instead of acetic anhydride, /3,7-unsaturated esters such as 388 are... 

Aromatic and heterocycHc compounds are formylated by reaction with dialkyl- or alkylarylformamides in the presence of phosphoms oxychloride or phosgene (Vilsmeier aldehyde synthesis) (125). The Vilsmeier reaction is a Friedel-Crafts type formylation (126), since the intermediate cation formed by the interaction of phosphoms oxychloride with formamide is a typical electrophilic reagent. Ionic addition compounds of formamide with phosgene or phosphoms oxychloride are also known (127). 

An interesting intramolecular Friedel-Crafts-type cyclization was developed by Pericas et al. Thus, aryl glycidyl ethers reacted to 3-chromanols as the only reaction product when treated with a catalytic amount of FeBr3 in the presence of AgOTf in CH2CI2 at room temperature (Scheme 9) [26]. The addition of a silver salt proved to... 

Protonic acid and Lewis acids can activate carbonyls to facilitate the addition of nucleophile attacks in aqueous media. The Prins reaction, reaction with alkyne, and Friedel-Crafts-type reactions have been discussed in related chapters in detail. 

An intermediate acylnickel halide is first formed by oxidative addition of acyl halides to zero-valent nickel. This intermediate can attack unsaturated ligands with subsequent proton attack from water. It can give rise to benzyl- or benzoin-type coupling products, partially decarbonylate to give ketones, or react with organic halides to give ketones as well. Protonation of certain complexes can give aldehydes. Nickel chloride also acts as catalyst for Friedel-Crafts-type reactions. 

Facile preparations of aryldichlorophosphines and their derivatives have been accomplished with aluminum chloride in a Friedel-Crafts-type reaction system. While the reaction system has been used for more than a century,55 significant modifications have been made for improvement of yield.56-59 Conditions have been investigated that allow the destruction of the aluminum chloride complex to generate the product aryldichlorophosphine without the addition of water (Equation 4.20),60-62 or with water to isolate the free phosph-onous acid.57 58... 

Gold-catalyzed direct C-H functionalizations enable the formation of polyalkylated arenes under mild conditions. In many cases, branched products are obtained. Two mechanisms are thought to operate with electron-rich arenes, an S si2-type mechanism via Au(lll) leads to the linear product. The branched product is obtained via a Friedel-Craft-type alkylation. A silver salt is often added and is believed to generate a more electrophilic Au(m) species. Often regioselectivities are poor and symmetric arenes are employed. Intramolecular variants as well as Michael additions are also known (Equations (72)-(74)).71,71a,71b... 

With halide catalysts of the Friedel-Crafts type (e.g., aluminum chloride or boron fluoride) in the presence of hydrogen halide the formation of the carbonium ion results in the addition of the proton from the promoter to the pi electrons ... 

The addition of BF3 OEt2 to a solution containing Ph3BiF2, allyltrimethylsilane and excess arenes induces a Friedel-Crafts-type allylation at low temperatures to yield allylarenes [36]. Benzene, toluene, anisole, p-xylene, and p-dimethoxyben-zene were all allylated with ease to give the corresponding allylation products, although diallylation could not be suppressed in the reaction with electron-rich... 

Typically, stoichiometric amounts of a Lewis acid such as AICI3 are required and produce stoichiometric amounts of salts and mineral acids (HX) as side products. Furthermore, undesired side reactions such as multiple alkylations and a low functional group tolerance are observed. With the need for more environmentally and economically benign processes, the development of Friedel-Crafts-type reactions using catalytic amounts of a Lewis acid catalyst is desirable. In addition, the substitution of benzyl halides for other environmentally friendly alkylating reagents constitutes an attractive goal. In particular, benzyl alcohols are suitable... 

The first systematic investigations of the catalytic Friedel-Crafts-type reaction with alcohols and olefines were performed by Yamamoto and colleagues. After reporting the development of a Pd-catalyzed method for the allylation of different naphthol derivatives [24], the authors used Mo(CO)g for the Friedel-Crafts-type alkylation of electron-rich arenes with allyl acetates [25], The same molybdenum catalyst was additionally used for a Friedel-Crafts-type alkylation of arenes using 1-phenylethanol and styrene as alkylating reagents [26], However, Mo(CO)g is toxic and must be handled under strictly inert conditions. Thus, more stable Lewis acids were necessary. 

Besides the high efficiency of this route, many styrenes are readily available. This widens the product scope for 1,1-diarylalkanes and would additionally complement the previously described benzyl-alcohol-based Friedel-Crafts-type alkylations. 

A Friedel-Crafts-type reaction can be carried out with hexachlorofullerene and, e.g., benzene, fluorobenzene, anisol or toluene, but due to steric hindrance not with mesitylene [85, 86]. Upon stirring benzene solutions of CgoClg with ferric chloride for 20 min, CgoPh5Cl can be obtained (Scheme 9.12). Replacement of the sixth chlorine is prevented by steric hindrance. This hindrance can be overcome by addition of the more reactive toluene to CgoPhsCl to give C6oPh5(C6H4CH3) [86]. 

Olefins are formed by dehydrogenation of the n-paraffin feed over the metallic hydrogenation-dehydrogenation function and are adsorbed on the acidic surface of the catalyst as carbonium ions by proton addition. After skeletal isomerization they are desorbed as isoolefins and subsequently hydrogenated to the corresponding isoparaffins. The net result (i.e., the formation of carbonium ions) of the action of metal and acid in dual function catalysis is, on pure Friedel-Crafts type catalysts, described by the scheme ... 

Benzyl acetate was prepared by addition of benzyl chloride (containing 0.6% pyridine as stabiliser) to preformed sodium acetate at 70°, followed by heating at 115°, then finally up to 135°C to complete the reaction. On one occasion, gas began to be evolved at the end of the dehydration phase, and the reaction accelerated to a violent explosion, rupturing the 25 mm thick cast iron vessel. This was attributed to presence of insufficient pyridine to maintain basicity, dissolution of iron by the acidic mixture, and catalysis by ferric chloride of a Friedel-Craft type polycondensation reaction to polybenzyls, with evolution of hydrogen chloride, which at 130°C would produce an overpressure approaching 100 bar. Previously the chloride had been supplied in steel drums containing 10% sodium carbonate or 3% sodium hydroxide solutions as... 

Probably the two most generally useful methods for effecting intramolecular acylation are by the Friedel-Crafts type of reaction on the acid chloride and the action of anhydrous hydrogen fluoride on the free acid. In addition to these methods, cyclizations have been effected by the use of sulfuric acid and other reagents. 

The ene reaction,3 6360-365 the addition of a carbon-carbon or carbon-oxygen double bond with concomitant transfer of an allylic hydrogen, can allow for chirality transfer.366-369 The reaction has similarities to the Diels-Alder reaction in that a o-bond is formed at the expense of a 7t-bond. In addition, the use of a Lewis acid as a catalyst allows for control of the relative stereochemistry (Scheme 26.14).370-372 Large-scale reactions will be complicated by the need to use either high temperatures or Lewis acids. In addition, thermal and Friedel-Crafts-type degradation products may be problematic with the use of these conditions.361373... 

Indoles can be used as radical acceptors instead of 63 [120, 121]. Simple and twofold reactions giving either 3-alkylindoles [120] or l,l-bis(3-indolyl)alkanes [121] were observed in 16-72% and 54-90% yield, respectively. In both methods the indole is subject to radical addition in 3-position. The resulting a-amino radical undergoes a further oxidation and deprotonation to the 3-substituted indole. In the case of twofold additions, the second indole unit is introduced by a subsequent polar Friedel-Crafts-type alkylation. 

---