Electron-rich arene

Chromium carbene complexes having electron-rich arenes tethered to the car-bene oxygen or carbon underwent photodriven intramolecular Friedel-Crafts acylation in the presence of zinc chloride (Eqs. 32 and 33) [118]. The process was highly regioselective, undergoing acylation exclusively para to the activating group. 

The FeCls-catalyzed Friedel-Crafts reactions of electron-rich arenes with imines or aziridines provide a facile and convenient route for the synthesis of p-aryl... 

Under Lewis-acid-catalyzed conditions, electron-rich arenes can be added to alkenes to generate Friedel-Crafts reaction products. This subject will be discussed in detail in Chapter 7, on aromatic compounds. However, it is interesting to note that direct arylation of styrene with benzene in aqueous CF3CO2H containing H2PtCl6 yielded 30-5% zram-PhCH CHR via the intermediate PhPt(H20)Cl4.157 Hydropheny-lation of olefins can be catalyzed by an Ir(III) complex.158... 

The arylation of electron-rich arenes, such as azulene (55)206 and heteroarenes, has been sporadically described. Under similar conditions phenols undergo arylation, which is preferably directed at the ort/zo-positions, probably due to the involvement of palladium phenolate intermediates.188,207 Polysubstitution occurs readily.208 The para-position can be attacked only with the sterically hindered 2,6-di-t-butylphenol.209 Similar ortho-diarylation of arenes bearing carbonyl groups (acetophenone, anthrone, benzanilide, etc.) shows that the or//zo-di reeling effect of the substituent is more important than its other electronic effects.189... 

Nucleophilic attack with electron-rich arenes and ethylene derivatives at C-7 of 5-methoxyfuroxano[3,4-d -pyrimidine 245 leads to 7-substituted 6,7-dihydro-5-methoxyfuroxano[3,4-r/]pyrimidines 246 (Equation 47) <2003JP0431>. 

However, the more important question of whether AN can be used in C,C-coupling reactions with nucleophiles remains open. It should be noted that Japanese researchers demonstrated in several studies that these transformations can be performed for benzene and certain electron-rich arenes (477). Just the same, this procedure requires severe conditions (the use of superacids at high... 

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... 

Furthermore, the first direct amination of benzene has been achieved and has generated the aniline derivative in an acceptable yield (Equation (103)). Recently, a cationic copper(i) complex 132-catalyzed nitrene transformation to the C-H bonds of the electron-rich arene was reported by Sadighi and co-workers (Equation (104)).285... 

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

Instead of stoichiometric amounts of Lewis acids (ZnCh, FeCh), small amounts of EGA (0.003-0.03 F) may catalyze acylation of electron-rich arenes when the electrophile precursor is used as solvent/co-solvent [40]. Yields in the range 22 to 95% are obtained, lowest when o-substitution has to take place as in 1,4-dimethoxybenzene. The regioselectivity is 75 to 98% [40]. 

The formation of six-membered or larger rings by intramolecular C-H bond insertion normally requires the attacked position to be especially activated towards electrophilic attack [1157,1158]. Electron-rich arenes or heteroarenes [1159-1162] and donor-substituted methylene groups can react intramolecularly with electrophilic carbene complexes to yield six- or seven-membered rings. Representative examples are given in Table 4.8. 

Instability of phenyl cation In case of haloarenes, the phenyl cation formed as a result of self-lonlsatlon will not be stabilised by resonance and therefore, S l mechanism Is ruled out. Because of the possible repulsion. It Is less likely for the electron rich nucleophile to approach electron rich arenes. Replacement by hydroxyl group... 

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. 

R = OAc). Besides benzene, electron-rich arenes as well as thiophenes were successfully benzylated. 

From a mechanistic point of view, it can be envisaged that this reaction proceeds via the desired benzylated pentanedione intermediate 14f. The subsequent intramolecular Friedel-Crafts alkylation of the electron-rich arene results in the quaternary benzyl alcohol II, which readily eliminates water to give the highly substituted indene 16 (Scheme 14). 

Scheme 27 Diastereoselective alkylation of propargyl alcohols with silyl enol ethers, allyl silanes and electron-rich arenes...

Similar to Rueping s procedure, Hua and coworkers developed a BiCl3-catalyzed synthesis of 1,1-diarylalkanes also starting from electron-rich arenes and styrenes [68]. They found that styrenes 37 could be transformed to the substituted cyclopentanes 39 if catalytic amounts BiCl3 were applied (Scheme 30). This reaction is believed to proceed via an intermolecular ene-reaction between styrene and the carbocationic intermediate I, followed by an intramolecular Friedel-Crafts alkylation of the resulting intermediate II. 

MTO in the presence of H2O2 produces complex 1, which has been used for catalytic oxidations of electron-rich arenes . An interesting example is the synthesis of vitamin K3 compound 121 (equation 83), where the two isomeric 2-methylnaphthoquinones are formed in a 7 1 ratio and a chemical yield of 121 of 85%. 

Electron-rich arenes react with quinone monoacetal 194 at the carbon a to the quinone carbonyl group with ring opening of the heterocycle. The reaction was mediated by catalytic amounts of TMSOTf furnishing the aryl addition products in good to excellent yields (53-99%) (Equation 64) <2001CPB1658>. 

At the beginning of the new millennium, Hashmi et al. presented a broad research study on both intramolecular and intermolecular nucleophilic addition to alkynes and olefins [18]. One of the areas covered by these authors was the isomerization of co-alkynylfuran to phenols [19]. After that, Echavarren and coworkers identified the involvement of gold-carbene species in this type of process, thus opening a new branch in gold chemistry [20]. And subsequently, Yang and He demonstrated the initial activation of aryl —H bonds in the intermolecular reaction of electron-rich arenes with O-nucleophiles [21, 22]. 

Auration proposed in the first mechanism (Scheme 8.8) is possible in similar species, as Kharasch [68] and Fuchita [69] observed in stoichiometric reactions. In both pathways, the same intermediate was formed and no [3-hydrogen elimination was observed and not only furan but other electron-rich arenes could react [70]. Although AuCl3 was the precatalyst used, it was not possible to determine whether Au(III) or Au(I) were the real catalytic species (Scheme 8.9). 

Related studies have recently been reported by the same author on propargyl steres reactions with dicarbonyl compounds or electron-rich arenes [135], to provide an atom-economical functionalization of carbon nucleophiles under catalytic conditions, using a very different method of addition catalyzed by Lewis acids [136]. 

The iodination of cross-linked polystyrene has been achieved using iodine under strongly acidic reaction conditions [55] or in the presence of thallium(III) acetate [61], but this reaction does not proceed as smoothly as the bromination. More electron-rich arenes, such as thiophenes [45,62-64], furans [46], purines [65], indoles [66], or phenols [67,68] are readily halogenated, even in the presence of oxidant-labile linkers (Figure 6.2). Polystyrene-bound thiophenes have also been iodinated by lithiation with LDA followed by treatment with iodine [64],... 

Cross-linked polystyrene can be acylated with aliphatic and aromatic acyl halides in the presence of A1C13 (Friedel-Crafts acylation, Table 12.1). This reaction has mainly been used for the functionalization of polystyrene-based supports, and only rarely for the modification of support-bound substrates. Electron-rich arenes (Entry 3, Table 12.1) or heteroarenes, such as indoles (Entry 5, Table 15.7), undergo smooth Friedel-Crafts acylation without severe deterioration of the support. Suitable solvents for Friedel-Crafts acylations of cross-linked polystyrene are tetrachloroethene [1], DCE [2], CS2 [3,4], nitrobenzene [5,6], and CC14 [7]. As in the bromination of polystyrene, Friedel-Crafts acylations at high temperatures (e.g. DCE, 83 °C, 15 min [2]) can lead to partial dealkylation of phenyl groups and yield a soluble polymer. 

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