Triflates Friedel-Crafts reaction

Indium trichloride349-351 is a mild Lewis acid that is effective for various kinds of Lewis-acid-catalyzed reactions such as Diels-Alder reactions (Scheme 85), aldol reactions, and Friedel Crafts reactions. Since indium trichloride is stable in water, several aqueous reactions have been investigated (Scheme 85) indium(III) triflate is also used as a Lewis acid. 

Enantioselective Michael-type indole Friedel-Crafts reaction with a,P-unsaturated acyl thiazole has been disclosed <07JA10029>. Reaction of indole 127 and 128 in the presence of 10% mol of bis(oxazolinyl)pyridine-scandium(III) triflate complex 129 in acetonitrile at -40 °C affords 130 with high level of enantioselectivity. 

There are few studies on the metal triflate-catalyzed addition of pyrroles to a, 1-unsaturated compounds <2001 AGE 160, 2001TL8063>. The Friedel-Crafts reaction of homochiral pyrrole derivatives 450 with a,P-unsatu-rated esters catalyzed by metal triflates furnished conjugated addition products 451 in good yields without racemiza-tion (Equation 107) <2004S2574>. The addition worked regioselectively at C-5 of pyrrole. The best yields were obtained by using yttrium triflate and methyl 4-phenyl-2-oxobut-3-enoate. The diastereoisomers were separated by column chromatography. 

Thio- and selenoacetals and esters are excellent substrates for mild Friedel-Crafts reactions, because of the affinity of sulfur and selenium for copper (Sch. 23). Anisole was readily acylated with methylselenoesters 94 at room temperature with activation by CuOTf to affordpnra-substituted (> 95 %) derivatives 95 [50,51]. Mercury(II) and copper(II) salts, which were effective for the activation of selenyl esters for reaction with alcohols, amines, and water, were not effective for the Friedel-Crafts reaction. Aromatic heterocycles 96 could be acylated in high yields, and the alkylation product 100 was obtained from dibutylthioacetal 99 and anisole. Vedejs has utilized this methodology in the cyclization of 101 to afford 102 in 77 % yield [52]. This intramolecular variant did not require the use of the more reactive bis copper triflate-benzene complex. 

Rare earth metal triflates are recognized as a very efficient Lewis acid catalysts of several reactions including the aldol reaction, the Michael reaction, allylation, the Diels-Alder reaction, the Friedel-Crafts reaction, and glycosylation [110]. A polymer-sup-ported scandium catalyst has been developed and used for quinoline library synthesis (Sch. 8) [111], because lanthanide triflates were known to be effective in the synthesis of quinolines from A-arylimines [112,113]. This catalyst (103) was readily prepared from poly(acrylonitrile) 100 by chemical modification. A variety of combinations of aldehydes, amines, and olefins are possible in this reaction. Use of the polymer-supported catalyst has several advantages in quinoline library construction. 

Friedel-Crafts reactions. For alkylation of arenes with secondary alkyl triflates at 80 the Sc(OTf)j catalyst can be reused without significant loss of activity. Direct acylation of 1-naphthol at C-2 and Fries rearrangement of 1-naphthyl esters are effected by... 

In older applications of aluminum species in the Friedel-Crafts reaction ADC 3 (X = C1, Br, I) have been used as catalysts [6], Effects of covalently-attached strongly electron-withdrawing groups on the reactivity of aluminum(III) were investigated. The tris(triflate) catalyst Al(OTf)3 was originally devised by Olah and coworkers (Scheme 6.74) [96]. As expected, tris(trifryl)imide catalyst 102 had more pronounced catalytic efficiency, because of its greater Lewis acidity (Scheme 6.75) [97]. 

Indium(III) chloride and indium(III) triflate have been introduced to organic syntheses as versahle Lewis acids. They are stable in water, and catalyze a variety of organic reachons, e.g. the Diels-Alder reaction, the aldol reaction, Michael addi-hon, the Friedel-Crafts reaction, and other organic transformations. 

Mixtures of CF3S03H and the triflates of B, A1 or Ga form a new superacid system, i.e. CF3S03H2 + [E(0S02CF3)4]- (E = B, A1 or Ga), which show superior catalytic activity in isomerization of alkanes, in trans-bromination and trans-alkylation of aromatics and in other related Friedel-Crafts reactions as compared with CF3S03H alone30-33. The relative reactivity sequence is B > Ga > Al. The triflates E(0S02CF3)3 were prepared from the reaction of EX3 (X = Br, Cl) with CF3S03H33. 

Influence of the Catalyst. Several different types of aromatic reactions are catalyzed by Lewis acids, including alkylation, polymerization, isomerization, acylation, and halogenation. The dependence of these reactions on various Lewis acids is shown in Table 12.11. This table shows a few common Lewis acids and the type of reaction(s) for which each is best suited. The relative strength of Lewis acids was discussed in Section 2.3. Olah gives a comprehensive list of Lewis acid catalysts, and includes several typical synthetic applications. Metal alkyl catalysts are also effective catalysts, but the aromatic substrate is usually converted to a mono-, di-, or trialkyl derivative. Both metal halides and their alkyl derivatives are effective Friedel-Crafts catalysts, as shown in Table 12.11,m as are common inorganic and organic acids. Triflate derivatives are trifluorosulfonate ester (—S02CF3 OTf) can be prepared with various metal counterions. Triflates are very effective catalyst in Friedel Crafts reactions. Some of the more common catalysts are B(OTf)3, Al(OTf)3, and Ga(OTf)3.ll3... 

Non-chloroaluminate ILs, which are in general poor nucleophiles, have proven to be attractive alternative media for Lewis acid catalyzed reactions. ILs may have a reaction rate accelerating effect, and they may improve selectivity and facilitate catalyst recovery. This is the case for scandium triflate catalyzed Diels-Alder cycloaddition [8,9], three-component (aldehyde, aniline, triethylphosphite) synthesis of a-aminophosphonates [10], Claisen rearrangement and cyclization reactions [11], or Friedel-Crafts reactions [12, 13]. 

Huorous compounds are also potentially useful as additives to promote organic reactions in carbon dioxide. For example, a fluorous alcohol RfCH20H assists asymmetric hydrogenations with non-fluorous ruthenium BINAP catalysts, and a fluorous aryl alkyl ether (C8F17C6H4-P-OC12H25) does so in scandium-triflate-catalyzed aldol and Friedel-Crafts reactions. These additives are presumed to act as solubilizers or emulsifiers to promote contact among the various reaction components. Since they are fluorous, they can be readily recovered from the otherwise organic reaction mixtures for reuse. 

There has been a review of asymmetric Friedel—Crafts reactions. It has been shown that the rhodium-catalysed reaction of potassium phenyltrifluoroborate with A-tosyl ketimines may lead to products such as (18) with high enantioselectivity. (g) The reaction of A-t-butanesuUinylimino esters with arenes to give products (19) is catalysed by Lewis acids, such as indium triflate, and may lead to enantio-metrically enriched a-glycines. The intramolecular alkylation of hydrogenated 0 tetralins, shown in Scheme 2, using iron(III) or aluminium(III) catalysts yields cis-hexahydrobenzophenanthridines. Formation of a stabilized carbocation intermediate is... 

Highly enantiosele ctive annulation reactions of (tert-butyldiphenylsilyl)allenes with ethyl glyoxylate using bis(oxazolinyl)pyridine-scandium triflate complex was described [120]. This [3 + 2] cycloaddition gave the corresponding dihydrofurans in moderate to high yields with high enantioselectivities (Scheme 12.54). The vinyl-silane functionality was acylated in Friedel-Crafts reaction with acetyl chloride to produce a-alkoxyenone. 

Regioselective Friedel-Crafts reaction with unsymmetrical alkynes was reported. A reaction of phenylacetylene with p-xylene afforded gem-diarylethylene (71) selectively (Equation 30) [35]. Zirconium triflate showed much higher catalytic activity than that of chloride. Hf-catalyzed reaction of benzene with 1-phenylpropane in ionic liquid produced 1,1-diphenylpropene (72) in excellent yield with excellent regioselectivity (Equation 31) [36]. 

Chiral Cu(II)/bisoxazoline complexes have proven efficient in catalyzing Friedel-Crafts reactions to a number of substrates. Cu(OTf)2/t-Bu-bisoxazoline (13) promotes addition of a variety of electron-rich aromatic compounds (11) to ethyl glyoxylate (12) (Scheme 17.2) [5]. An interesting detail in this work was the importance of triflate as the counterion. When Cu(Sbp6)2 was employed as the Lewis acid, the yield and enantioselectivity was dramatically decreased. Furthermore, the choice of solvent had a significant effect on reactivity and selectivity. CH2CI2 generally led to improved chemical yield, while THF provided optimal enantioselectivities. 

Aliphatic nitriles react slowly with phenols and phenyl ethers in the presence of trifluoromethanesulphonic acid to give ketones after hydrolysis, in a variation of the Houben-Hoesch reaction. The crystalline complex of copper(i) triflate and benzene induces the acylation of aromatic substrates with selenol esters, affording a transition-metal mediated version of the Friedel-Crafts reaction. Aromatic carboxylic acids can be converted into symmetrical diaryl ketones in good yield by treatment of their 5-(2-pyridyl)thioesters with bis-(l,5-cyclo-octadiene)nickel [equation (15)]. In contrast to other methods for preparing symmetrical aromatic ketones, this method allows their preparation from a single starting material. 

Friedel-Crafts reactions of the trichlorocyclopropenium cation (79) with unsaturated substrates are very sensitive to the nature of the counterion. The triflate salt is ideal with aromatic substrates to give triarylcyclopropenium systems. Hexa-chloroantimonate is the ion of choice with olefinic and acetylenic systems. This opens up a pathway to the previously unknown di- and tri-vinylcyclopropenium... 

Y(OTf)3, as all other metal triflates, is able to catalyze Friedel-Crafts reactions in the presence of water. But it may also exhibit activity in more particular Friedel-Crafts reactions. For example, it showed activity in the acetylation at the 4-position of 3-phenylsydnone (Equation (8.25)) with acetic anhydride using either acetonitrile or acetic anhydride, in excess, as solvent [53]. 

Although the Lewis acids used as co-reagents in Friedel-Crafts acylations are often referred to as catalysts, they are, in fact, consumed in the reaction, with the generation of strong acids. There has been considerable interest in finding materials which could function as true catalysts. Considerable success has been achieved using lanthanide triflates. ... 

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