Carboxylic-triflic anhydrides

Acylation of electron-rich aromatics is reported to occur efficiently and very easily through mixed carboxylic-triflic anhydrides without any catalyst. The reaction can be applied to methoxy- and alkylarenes and thiophene, with acetic and benzoic acid, in a neat mixture, or in nitromethane (65%-98% yield) at room temperature or at 45°C. 

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. 

An efficient and ecofriendly procedure for the small-scale acylation of ferrocene with carboxylic acids is based on the in situ production of the mixed carboxylic-triflic anhydride (Table 4.15 see also Chapter 3). The reaction is simply performed by adsorbing ferrocene on the surface of activated alumina (preheated at 150°C for 3 h) and adding a mixture of carboxylic acid and trifluoroacetic anhydride (TFAA) at room temperature for a selected time. Products 40 are recovered in 55%-98% yield simply by elution with diethyl ether. 

The chloride of triflic acid (trifluoromethanesulfonyl chloride) is an effective sulfonylating agent Like triflic anhydride, it usually reacts with alcohols and other nucleophiles with the formation of the corresponding derivatives of tnflic acid [69] However, in some reactions, it acts as a chlorinating reagent [98] The reactions of tnfluoromethanesulfonyl chloride with 1,3-dicarbonyl compounds or some carboxylic esters in the presence of a base result m the formation of chlonnated products in high yields (equation 49)... 

Several different nucleophilic displacement reactions of ring substituents were utilized in the synthesis of 3-azido-oxetane-2-carboxylates (Scheme 12) <2001TL4247>. The triflate ester 66, prepared from the corresponding trans-/3-hydroxy ester and triflic anhydride, was displaced by reaction with sodium azide, and inversion of configuration, to... 

Recently, some modified reaction conditions have been proposed to improve yields, particularly for aromatic carboxylic acids. A phosphonium anhydride reagent (11) made from triphenylphosphine oxide and triflic anhydride appears to induce reaction at low temperatures in common solvents giving high yields of 2-arylbenzi midazoles in 30-60 min at room temperature (Scheme 3.1.12) [78]. 

Polymer-supported triphenylphosphine ditriflate (37) has been prepared by treatment of polymer bound (polystyrene-2% divinylbenzene copolymer resin) triphenylphosphine oxide (36) with triflic anhydride in dichloromethane, the structure being confirmed by gel-phase 31P NMR [54, 55] (Scheme 7.12). This reagent is effective in various dehydration reactions such as ester (from primary and secondary alcohols) and amide formation in the presence of diisopropylethylamine as base, the polymer-supported triphenylphosphine oxide being recovered after the coupling reaction and reused. Interestingly, with amide formation, the reactive acyloxyphosphonium salt was preformed by addition of the carboxylic acid to 37 prior to addition of the corresponding amine. This order of addition ensured that the amine did not react competitively with 37 to form the unreactive polymer-sup-ported aminophosphonium triflate. 

Related anchored l,l,3,3-tetraphenyl-2-oxa-l,3-diphospholanium bis-triflate (39) has been prepared by reaction of brominated poly(styrene-co-divinylbenzene) resin 38 with the phosphorous anion generated from l,2-bis(diphenylphosphino)ethane and sodium naphthalenide followed by further oxidation and reaction with triflic anhydride (Scheme 7.13) [55]. This supported reagent has also been employed, to a lesser extent than 37, for the formation of esters and amides by reaction of carboxylic acids with primary alcohols and amines, respectively. 

Trifluoroacetic and triflic anhydrides can be utilized to promote acylation of aromatics with carboxylic acids without any metal catalyst. Thus, the trifluoroacetic anhydride (TFAA)-promoted cycloacylation of conveniently functionalized carboxylic acids prepared from Baylis-Hillman adducts... 

Optically active 2-(l-aminoalkyl)-thiazole-4-carboxylate (242), a precursor for the syntheses of dolastatin 3 isomers, is readily prepared from 227 according to the series of reactions outlined in Scheme 34 [84]. In the pivotal reaction, 238 239, it is crucial to use ethyloxirane as an additive in order to trap the liberated hydrobromic acid and thereby stop the reaction at the intermediate 239. Dehydration with triflic anhydride forms optically pure thiazole 240. Without ethyloxirane, thiazole 240 is produced directly from 238 with 40-60% ee. 

To prepare 4-iodooxazoles, Vedejs protocol with DMPU cosolvent allows for efficient synthesis. When DMF is used as the solvent, 2,4-unsubstituted oxazoles can be regioselectively brominated at the 4-position widi NBS on kilogram scale. Hunsdiecker reaction of a C4-carboxylic acid also provides the C4 bromide. With a substituted C2 position, Nicolaou and co-workers achieved chlorination of the C4 position using NCS to prepare an intermediate in the partial synthesis of diazonamide Similar to C2 trifloyloxazole synthesis, trapping of 4-oxazolones with triflic anhydride yields 4-trifloyloxazoles. These triflates, in contrast to 2- or 5-trifloyloxazoles are stable and can generally be utilized in cross-coupling reactions. 

Carboxylic acid anhydrides. A soln. of triflic anhydride in ethylene dichloride added dropwise to a soln. of Ph3PO in the same solvent at 0° under N2 after 15 min a soln. of / -toluic acid in ethylene dichloride added followed by EtjN, and stirred for 15 min - p-toluic anhydride. Y 93%. Redox side reactions are avoided, and ketones, esters and ethers unaffected. F.e. inch ketenes, carboxylic acid esters (incl. aryl esters) and amides, amidines from carboxylic acid amides, benzimidazoles, and intramolecular ar. acylation, also using N-diphenylphosphinyl-N -methylpiperazine (without the need for an additional base), s. J.B. Hendrickson, M.S. Hussoin, J. Org. Chem. 54, 1144-9 (1989) alternative prepn. of reagents cf. D. Crich, H. Dyker, Tetrahedron Letters 30, 475-6 (1989). 

Carboxylic acids are more convenient as acylating reagents in comparison to acid chlorides or anhydrides [30]. The formation of ketones in the reaction of thiophene with acetic or benzoic acid in the presence of triflic anhydride, without involving a metallic catalyst, was complete at room temperature in only minutes with high yields. Acetylatitm with acetic acid proceeded in solvent-free conditions, but benzoic acid needed nitromethane as the solvent. The reaction mechanism is believed to involve the formation of a mixed anhydride between the carboxylic acid and triflic anhydride which then reacts with thiophene. Triflic acid is formed as a side product (Scheme 10) [30]. 

Nitronium triflate (Tf0N02) which is readily generated in dichloromethane from tetramethylammonium nitrate (McqN NOa") and triflic anhydride, can be used as a nitrating agent. Its application for the nitration of methyl thiophene-2-carboxylate afforded 5-nitro- and 4-nitro-substituted isomeric products in 91% combined yield (Scheme 89) [137]. 

One-carbon Homologation of Carboxylic Acids. l-[(Tri-methylsilyl)methyl]benzotriazole converts benzoyl chlorides to the corresponding (benzotriazol-l-yl)methyl aryl ketones in high yields (see eq 1). Treatment with triflic anhydride and 2,6-lutidine in CH2CI2 converts these ketones into their enolate triflates in 83-95% yields (eq 4). In the subsequent steps, the triflates are treated with sodium methoxide and then with ethanolic HCl to afford ethyl esters of the corresponding arylacetic acids in 89-98% yields (eq 5). The proposed reaction mechanism involves elimination of trifluoromethanesulfonic acid with sodium methoxide and final alcoholysis of the obtained l-(arylethynyl)benzotriazole intermediates with ethanolic HCl. A comparable classical method for one-carbon homologation of carboxylic acids, the Amdt-Eistert reaction, involves difficult to handle diazomethane and Q -diazoketones. ... 

Later a modified procedure for the preparation of 3,6-bis(trifluoromethyl) phthalodinitrile 83b was elaborated [67] (Scheme 23), which starts from 2,5-bis(trifluoromethyl)benzoyl chloride 86 and includes its conversion to N,N-diethylamide 87, carboxylation of the latter in the presence of 2,2,6,6-tetramethylpiperidine, followed by direct formation of the imide 81b ( 59 % overall yield). The diamide 82b obtained with liquid NH3 treatment (28 % yield), was then converted to dinitrile 83b with triflic anhydride in dioxane (yield... 

Mixed anhydrides of a carboxylic acid and trifluoroacetic or triflic acids... 

New Soluble Catalysts. Trifluoromethansulfonic acid (triflic acid, TfOH)42 and acyl triflates, that is mixed anhydrides of carboxylic acids and triflic acid,43 44 were first reported to be effective for Friedel-Crafts acylation in 1972. Significantly lower yields (<30%) were obtained with other Brpnsted acids. High activities were also observed for perfluorobutanesulfonic acid.37... 

Studies on mixed anhydrides of carboxylic acids and triflic acid have shown them to be extremely powerful acylating agents.350 Similarly, higher perfluoroalkanesulfonic acids also form mixed anhydrides.351... 

---