Electron-rich arenes acylation

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. 

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]. 

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. 

Electron-rich arenes are suitable nucleophiles for this reaction as well. Thus, the addition of arenes to imines has been described in both intra- (equation 121) and intermolecular (equation 122) fashion catalyzed by AuCb/AgOTf The yields were increased in the intramolecular version by acylation of the amide intermediate to give acylamides. In... 

Friedel-Crafts acylation. Electron-rich arenes undergo acylation with AcCl using Zn as promoter. 

In the presence of a stoichiometric amount of SbCls, Friedel-Crafts acylation proceeds with acyl hahdes and acid anhydrides [47], SbCls also promotes the Fries rearrangement of phenyl acetates [48], The electrophilic acylation of fluoro-olefins with acetyl fluoride or benzoyl fluoride is promoted by SbFs in liquid SOy [49], The Friedel-Crafts acylation of benzene and electron-rich arenes is successfully catalyzed by SbCl5-AgClO4 [50], SbCl, Ar.BCl [51], SbCl5-LiClO4 [52], or CaCI, AgSbFg [53] (Scheme 14,19), Acyl chlorides, acid anhydrides, and acyl enolates are used as sources of acyl groups. 

The mixed carboxylic-triflic anhydride produced between the acyl chloride and triflic acid has been earlier described to give electrophilic acylation without any catalyst.This acylation method is advantageous in terms of the mild conditions employed and the easy availability of acyl chlorides. The aromatic substrates are mainly limited to electron-rich arenes. However, the methodology can be applied to unactivated aromatics such as benzene and chlorobenzene under special conditions. 

Acylation of electron-rich arenes with AC, BC, and benzotrichloride can be performed in the presence of hydrated zirconia. The catalyst is prepared by treatment of an aqueous solution of zirconium(IV) oxychloride octahydrate (ZrOCl2 x 8H2O) with aqueous sodium hydroxide at room temperature, followed by heating the precipitate at 300°C for 5 h. The acetylation is performed in 1,2-dichloroethane at 60°C, whereas benzoylation is carried out under solventless conditions at 120°C (Table 4.16). It is remarkable that naphthalene is benzoylated selectively at the 1-position. The catalyst is recovered by filtration and reused three times with no loss of activity and selectivity in all cases. 

N-Acylanilines. When electron-rich arenes are treated with a carboxylic acid, hydroxylamine hydrochloride in PPA, several reactions occur in sequence. These are the Friedel-Crafts acylation, oxime formation, and Beckmann rearrangement. Anilides are obtained in 45-95% overall yields (11 examples). 

Fluoroamine reagents. The reaction of BF3 etherate with a-fluoroamines produces salts (1) that are similar to Vdsmeier reagents. These salts acylate electron-rich arenes. 

Toste observed the aromatization of the new cycle in a different type of reaction, in which the allene had been formed in situ by acyl migration of a propargyl carboxylate. In a similar vein, cyclizations of diynes bearing propargyl carboxylates have been described to synthesize dienes and pyrones (equation 90). In the last case, a new cascade allows the intermolecular addition of electron-rich arenes. ... 

Reaction of phenol derivatives with acyl chlorides in acidic conditions may result in O-acylation or C-acylation, either directly or via a Fries rearrangement. Studies of acylations in acetonitrile using trifluoromethanesulfonic acid (trifllc acid) have shown that O-acylation is favoured at a low acid concentration, while a high acid concentration favours C-acylation. It has also been shown that A-hydroxysuccinimidyl and phenyl esters of benzoic acids are activated by triflic acid and can be used to acylate electron-rich arenes such as ferrocene or pyrene the reactive acylating intermediate is likely to be an acyl triflate or its protonated form. In a polyphosphoric acid medium, the rearrangement of 1,5- 1,8- and 9,10-diacetylanthracenes leads to the formation of the ring-closed product (56). DFT calculations support the conclusion that the reaction involves the intermediacy of 1,9-diacetylanthracene formed under kinetic rather than under thermodynamic control. ... 

Palladium-catalyzed dehydrogenative cis double phosphorylation of 1-octyne with the /7-phosphonate (88) leading to (Z)-l,2-bisphosphoryl-octene (89) has been sueeessfully carried out by Han et al (Scheme 28). p-Aryl-p-ketophosphonates (90) have been efficiently prepared in good yields using the TBAA/H3P04-mediated acylation of electron-rich arenes with phosphonoacetic acids. The conditions enabled preparation of (90) without use of strong bases, cryogenics or anhydrous and inert atmosphere. 

In contrast to the acyl- and sulfonylnitrenes described in this section, arylnitrenes produced thermally or photolytically from aryl azides, including those bearing strongly electron-withdrawing substituents (e.g., CN, N02, CF3), fail to promote ring expansion of arenes to 1H-azepines, although intermolecular substitution of electron-rich substrates, e.g. mesitylene and A.TV-dimethylaniline, have been noted.167... 

As can be seen in the scheme below, a series of substituted 2-(2-aminothiazol-4-yl)-benzo[ ]furans with inhibitory activity for leukotriene B4 were made from benzofurans via acylation, followed by Hantzsch thiazole formation <070BC3083>. 2-Substituted benzo[ ]furans could also be generated via an aerobic oxidative coupling of 2-unsubstituted benzo[ ]furans with arenes through the palladium-catalyzed double C-H activation <07OL3137>. In addition, 2,3-diarylbenzo h I uran could be constructed by a palladium-catalyzed arylation of benzo[6]furan with an aryl chloride in the presence of a bulky, and electron-rich phosphine <07OL1449>. 

Bismuth(lll) salts such as BiCls, BiBrj, Bi(OCOR)3, and Bi (OTf), [166] have been widely used as Lewis acid catalysts to mediate C-C bond formation. Bi (OTf) 3, Bi2O3, and BiCl, catalyze Friedel-Crafts acylation with acyl chlorides or acid anhydrides [167]. Both electron-rich and electron-deficient arenes are acylated in high yields under catalysis by Bi(OTf)3 (Scheme 14.82). Under microwave irradiation the catalytic activity of BiX3 (X = C1, OTf) in the acylation of aromatic ethers is enhanced [168]. The N-acyl group of p-substituted anilides migrates to the ortho position of the aromatic nucleus under BiCls catalysis [169]. Treatment of 2,3-dichloroanisole with the ethyl glyoxylate polymer in the presence of a catalytic amount of Bi(OTf)3 affords an a,a-diarylacetic acid ester quantitatively (Scheme 14.83) [170]. 

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