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Treatment of aryl sulfoxides and sulfonanilides with trifluoroacetic anhydride resulted in the dehydrative metal-free construction of the corresponding unsymmetrical biaryls. The reaction would proceed via (1) the activation of aryl sulfoxide with the anhydride, (2) interrupted Pummerer reaction of the resulting arylsulfonium with sulfonanilide, (3) [3,3] sigmatropic rearrangement to cleave the transient S–N bond and to form the prospective biaryl C–C bond, and (4) global aromatization. The choice of the amino protecting group is crucial, and only N-sulfonylanilines, i.e., sulfonanilides, could participate in the formation of biaryls.

Methods for generating tert-alkyl organoboron species are in high demand as they are invaluable intermediates for the synthesis of quaternary carbon centres. Herein we report investigations into generation of tert-alkyl organoboron species using imidoyl chlorides as reagents in the organoboron cyanidation reaction. Although alkenyl side-products predominate in particularly hindered cases, tert-alkyl organoboron species can be successfully generated for less hindered examples.

A Pummerer rearrangement of 2,3-dideoxy-3-alkyl/arylsulfinyl-arabino-hexopyranosides is reported. Treatment of sulfinyl-arabino-hexopyranoside derivatives, obtained through oxidation of the corresponding thio-derivatives, with trifluoroacetic anhydride (TFAA)/pyridine led to a facile formation of 2,3-dideoxy-3-alkyl/arylthio-hex-2-enopyranosides. Upon conversion of sugar vinyl sulfides to vinyl sulfoxides, conjugate addition reactions were conducted with alkoxides, to afford 3-deoxy-3-alkyl/arylsulfinyl pyranosides, in the manno-configuration exclusively. Whereas the conjugate addition reaction did not proceed with ether protecting groups, ester protecting groups and free hydroxyl groups in the sugar vinyl sulfoxide permitted the reaction. (C) 2012 Elsevier Ltd. All rights reserved.

By sulfonation of 3-R-1-adamantylacetic acids 1 with H2SO4 in trifluoroacetic anhydride (TFAA), the previously unknown α-(3-R-adamantyl)sulfoacetic acids 2 were obtained. In the case of 1-adamantylacetic acid 1a, the use of ∼1 equiv of H2SO4 led to only 1-adamantylacetic acid 2a, while with an excess of the reactant the hydroxylation of the adamantane tertiary C–H bond also occurred. It is assumed that the bis(trifluoroacetyl)sulfate generated in situ from H2SO4 and TFAA is responsible both for sulfonation and oxidation steps. The adamantylated sulfoacetic acids were used for the preparation of a series of derivatives by modifications of carboxylic, sulfonic acid, and tertiary adamantane OH-groups. Due to the use of TFAA as a medium, a series of derivatives of sulfoacetic acids was obtained directly from acids 1 within one-pot procedures. Some of the synthesized compounds possess anti-HSV activity.

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins react with electron-rich aminoheterocycles, dimethyl 1,3-acetonedicarboxylate, hydrazines, alkyl thioglycolates, and methyl sarcosinate to give a variety of 3,4-heteroannulated coumarins. The starting materials were prepared by the reaction of 4-hydroxycoumarin with trifluoroacetic anhydride and methyl 2-chloro-2-oxoacetate in the presence of trimethylsilylchloride. An NMR study and X-ray crystallographic analysis are reported.

The tandem reaction of cyanoacetanilides with triflic anhydride in DMF proceeded at room temperature to afford 3-formyl-4-hydroxyquinolin-2(1H)-ones in good to high yields. A detailed mechanistic study revealed that the tandem reaction proceeded via α-dimethylaminomethylenation, which promoted the subsequent Houben–Hoesch-type cyclization. Both α-functionalization and the cyclization steps were optimized, and a multi-gram scale synthesis of 3-formyl-4-hydroxyquinolin-2(1H)-one was achieved.

Efficient synthetic approaches to functionalized 5-(3-R-1-adamantyl)uracils and related compounds (R=OH, COOH, NH2, etc.) are described. The selective hydroxylation of the adamantane tertiary C–H bonds in 5-(1-adamantyl)uracils with H2SO4 in trifluoroacetic anhydride is used as the key step. Subsequent electrophilic reactions of 5-(3-hydroxy-1-adamantyl)uracils with N- and C-nucleophiles in CF3COOH, H2SO4 or H2SO4/AcOH media yielded derivatives with amide, amino, aryl, carboxy and thiourea groups in the adamantane core. The preliminary evaluation of the antiviral activity revealed that some of the synthesized species display moderate antiviral activity against HSV-1 (SI∼20) in Vero cells.

An easy route to the synthesis of 2-substituted-7-azaindole derivatives has been developed. The carbinol intermediate dissolved in DMF undergoes cyclization upon treatment with sodium hydride, trifluoroacetic anhydride, and trifluoroacetic acid at 120 °C in a straightforward and one-pot step. An alternative methodology using (CF3SO2)2O in acetonitrile in basic media followed by the addition of CF3COOH affords the expected 2-substituted azaindole in best yields.

When N -[2-(alkylsulfinyl)phenyl]-1 H -indole-2-carboxamides with varying degrees of indolic and amidic N-alkylation are heated in an inert solvent or treated with trifluoroacetic anhydride; only compounds in which the amidic nitrogen is methylated cyclize to indolo[3,2- b ]-1,5-benzothiazepinones ( 9 , 10 ). Successful cyclization is attributed to the ability of N -Me amides to readily adopt a conformation conducive to cyclization, which other derivatives are unable to achieve. The analogous 3-indoleanilide, N , N- dimethyl N -[2-(ethylsulfinyl)phenyl]-1 H -indole-3-carboxamide ( 17a ), undergoes SES/rearrangement to produce 10 upon heating in p -xylene. An intermediate 3 H -indolinium spirocyclic species is proposed to account for this result.

A trifluoroacetic anhydride-catalyzed opening of the oxirane system of glycidyl esters with a simultaneous migration of the acyl group provides a new, efficient entry to either 2-monoacylglycerols (2-MAG) or 1,3-symmetrical triglycerides (1,3-STG) as potential prodrug frameworks.

Pictet–Spengler condensation of 13 with tryptamine gave 14 , which was converted into 17 . Treatment of 17 with phenyl chloroformate resulted in 18 , which underwent transannular cyclization to give 19 . The more stable cyano-analog 22 was made by treating 18 with Tf2O/DMAP to generate 18f , and quenching the reaction with trimethylsilyl cyanide. Treatment of 22 with acryloyl chloride (excess) at 75°C gave 23 , which was directly treated with N-hydroxy-2-thiopyridone/Et3N to give 24 . Irradiation of 24 in the presence of t-BuSH resulted in reductive decarboxylation to give 26 and a small amount of the 2-thiopyridyl ether 25 . Protection of the aniline nitrogen in 26 required the use of triphosgene/pyridine followed by methanol. The final step for the conversion of 27 into 28 required conjugate reduction of the α,β-unsaturated ester followed by α-hydroxylation and gave 28 (11,12-demethoxy lahadinine B). Exposure of 26 to PhI(OAc)2/MeOH cleanly gave 26a , which was directly reduced with Zn/AcOH to 29 . Conversion of 29 into 30 proceeded as before, and when 30 was treated with AgBF4/THF followed by aqueous NaHCO3 it was converted into (±)-kopsidasine 2 , completely characterized as its derived N-oxide 2a . Treatment of 26 with AgBF4/THF followed by aqueous NaHCO3, gave 31 . Oxidation of 31 with m-chloroperoxybenzoic acid resulted in the N-oxide 32 which underwent fragmentation to give 33 when exposed to trifluoroacetic anhydride. When the diene 33 was treated with Mn(dpm)3 (cat)/PhSiH3/O2 in isopropyl alcohol at 0°C, it was converted into kopsijasminilam 4 . Peracetic acid in EtOAc (10%) was used to quench the AgBF4/THF conversion of 28 into 37 , and resulted in 42 / 42a (4:1, 65%) along with small amounts of 38 and 41c . Application of these procedures, with some modifications, to the 11,12-dimethoxy substituted systems gave (±)-lahadinine B 64 . Treatment of 64 with triethylsilane in the presence of trifluoroacetic acid cleanly converted it into 11-methoxykopsilongine 65 (93%). Treatment of (±)-lahadinine B 64 with AgBF4/THF followed by work-up with EtOAc/MeCO3H (10%) gave (±)-pauciflorine 6 and the double bond isomer 6a .

The title compounds have been prepared by treatment of 4-methoxy-3-phenylsulfinylmethyl-2 H -pyrone derivatives with trifluoroacetic anhydride, followed by basic work-up.

Titanium tetrachloride mediated dialkylation of acetic anhydride, trifluoroacetic anhydride or difluorochloroacetic anhydride by 1,8-bis(trimethylsilyl)-2,6-octadiene (BISTRO) leads, respectively, to dl -1-methyl-2,5-divinylcyclopentan-1-ol, dl -1-difluoromethyl-2,5-divinylcyclopentan-1-ol or dl -1-trifluoromethyl-2,5-divinylcyclopentan-1-ol. Esterification of these compounds with 4-methoxybenzocyclobutene-1-carboxylic acid and then pyrolysis led to 3-methoxy-12-oxa-17-vinylestra-1,3,5(10)-trien-11-one and to corresponding 18,18-difluoro or 18,18,18-trifluoro derivatives. Further transformations give rise to 3-methoxy-12-oxa-17-(2-oxoethyl)-18,18-difluoroestra-1,3,5(10)-trien-11-one and to the corresponding 18,18,18-trifluoro derivative.

Addition of trifluoroacetic anhydride to isocyanides proceeds smoothly to give after treatment trifluoropyruvamide derivatives in high yield.

The systematic studies of the reaction of aldonitrones with the NaI-TFAA system were performed. The reaction engaged was recognised as a previously known process called ‘the Beckmann rearrangement of nitrones’. Some mechanistic considerations on this transformation and competitive nucleophilic additions are presented in order to explain the origin of iodine release and its observed stoichiometry as well as of some products isolation. The intermediacy of C- and N-iodo species (including iodonium cations) in the presence of iodide anions, is postulated.

Various trifluoromethylated heterocycles can be prepared in good yield from carboxylic acid chlorides by reaction with pyridine and trifluoroacetic anhydride followed by capture of the intermediate trifluoroacyl ketene with suitable reagents.

Dimesitylboron stabilised carbanions react with diarylketones to give the corresponding alkenes in mild conditions with good yields. Reactions with aromatic aldehydes are more complex, but in all cases E-alkenes are available in good yields by trapping the intermediates with chlorotrimethylsilane followed by treatment with aq. HF/CH3CN. Treatment of the same intermediates with trifluoroacetic anhydride gives mainly the Z-alkenes. The design and mechanisms of these important processes are considered.

Treatment of β-monosubstituted vinylic sulfoxides 1 with trifluoroacetic anhydride in dichloromethane gave excellent yields of 1,2-bis(trifluoroacetoxy)thioethers 6. Mildly basic methanolysis of 2-alkyl-substituted 6 gave α-hydroxyaldehydes 11 as monomer-dimer mixtures; similar treatment of the 2-aryl analogues afforded aryl (hydroxymethyl) ketones 12. Compounds 11 underwent Wittig reactions with methoxycarbonylmethylenetriphenylphosphorane to give high yields of γ-hydroxy-α,β-unsaturated esters 13, predominantly as the E-isomers. β-Monosubstituted vinylic sulfoxides 1 possessing a β-aryl group, and β-disubstituted vinylic sulfoxides 3 reacted with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride to give 2-(phenylsulfenyl)acylals 14. These gave 2-phenylsulfenyl aldehydes 15 upon basic methanolysis, and the corresponding primary alcohols 16 on reduction with sodium borohydride. Reaction of both geometric isomers of enantiomerically pure vinylic sulfoxide 1o with TFAA gave racemic 6o as a mixture of diastereomers. Reaction of optically pure (E)- and (Z)-1p with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride gave acylal 19 in 10.5 and 23% e.e., respectively.

The fragmentation-coupling of catharanthine and vindoline by trifluoroacetic anhydride has been carried out under conditions which allow observation of intermediates and comparison of reactivity by low temperature NMR. These studies have confirmed or revealed the following facets of the mechanism of the reaction: (1) fragmentation of an intermediate derived from catharanthine-N-oxide which otherwise is stable at −40°C occurs rapidly on addition of vindoline; (2) other bases including tri-n-butylamine, N,N-dimethyl- 3-methoxyaniline, N,N-dimethyl-2-(2,4-dimethoxyphenyl)ethylamine and 10-trifluoroacetyl- vindoline also accelerate fragmentation; (3) the stereoselectivity of coupling is controlled in part by the different rates of reaction of vindoline with separate precursors of anhydrovinblastine and 16′ -epi-anhydrovinblastine; (4) Na-methylcatharanthine-Nb-oxide undergoes fragmentation in a manner analogous to catharantine-N-oxide but there is an observable intermediate which can not be detected in the latter case; (5) the rate of fragmentation of Na-methylcatharanthine-Nb-oxide is also subject to some acceleration by base; (6) several products formed from the final fragmentation with the previous representation of the fragmentation-coupling mechanism but contribute new details.

A large-scale synthesis of 3,4,5-tri-0-acetyl-2,6-anhydro-L-mannono-and-D-gulonothioamides (5, 6) has been achieved from the corresponding nitriles. The Hantzsch reaction of (5) or (6) with ethyl bromopyruvate afforded the expected thiazoles (7.8) only in a low yield along with furan derivatives (9-11), the formation of which is rationalized by an acid-catalysed rearrangement-elimination process. The some Hantzsch reaction in the presence of barium carbonate yielded hydroxythiazolines (16,17). Attempted dehydration of (16) or (17) with trifluoroacetic anhydride or trifluoroacetic anhydride/pyridine resulted in the formation of pent-1′-enopyranosylthiazoles (18-20). Deprotected thioamides (24,25) furnished with ethyl bromopyruvate thiazoles (27,28). The obtained thiazole esters (7,8, 18-20. 27,28) were transformed into new tiazofurin analogues (12, 13, 21- 23).

Acylation of methyl and benzylethers of orcinol with the same ethers of phloroglucinol carboxylic acid using trifluoroacetic anhydride (TFAA) in chloroform or dichloro methane afforded both unsymmetrical and symmetrical benzophenones. Magnetic resonance measurements were performed on the reactions between various deuterium labelled methylethers of phloroglucinol and phloroglucinol carboxylic acid. The reaction was found to proceed via several equilibria resulting in a total scrambling of the aromatic rings around the carbonyl function. The occurrence of an intermediate in the reaction was observed and is thought to consist of an ion pair between a protonated benzophenone and trifluoroacetate ion which rapidly catalyses an exchange between TFAA and TFA.

Reaction of various sulfoxides 9 , with nitriles 10 in presence of trifluoroacetic anhydride and trifluoroacetic acid gave the corresponding amides 11 via a Ritter reaction on Pummerer intermediate derived from the sulfoxides.

5-(2'-Benzamidoacyloxy)thiazoles are formed by the reaction of N-thiobenzoyl-α-amino-acids with trifluoroacetic anhydride. Corresponding esters on similar treatment undergo isosteric S-O exchange, giving N-benzoyl-α-amino-acid esters. While these are further examples of the differences shown in the reactions of N-(2-carboxyalkyl)thiobenzamides compared with their benzamide analogues, Nα-thiobenzoyl-α-amino-acid amides are found to undergo cyclisation in trifluoroacetic anhydride to give 5-trifluoroacetamido-thiazoles, following the same reaction path as their N-benzoyl analogues. Terminal N-thiobenzoyl dipeptides give 5-(N-2-carboxyalkyl) trifluoroacetamido-thiazoles on treatment with trifluoroacetic anhydride, and it is established that trifluoroacetic anhydride fails to cleave the amide group of terminal N-thioacyl dipeptides, and is therefore not a suitable reagent for Edman-type sequence analysis of polypeptides. The present work completes a project establishing routes from α-amino-acids to thiazoles carrying a heteroatom (O, N or S) at the 5-position.

Diacylimidazolium ions yield adducts with aromatic compounds. Thus the N,N'-diacetylimidazolium ion and indole gives 1,3-diacetyl-2-(3-indolyl)-4-imidazoline. Less reactive substrates such as thiophene, anisole and 1,3-dimethylbenzene fail to react with this reagent but do form adducts (e.g. 1,3-bis-(trifluoroacetyl)-2-(2-thienyl)-4-imidazoline) with an imidazole/trifluoroacetic anhydride reagent. All of the adducts could be converted to the corresponding aldehyde under mild conditions. The synthetic scope of the new synthesis is similar to that of the Vilsmeier-Haack reaction.

Interaction of the pyrrolizine 3 with cyanogen bromide in a tetrahydrofuran/water mixture affords addition to the enamine double bond with formation of 5 which can be aromatized to 6 by silica gel. Reaction of 6 with cyanogen bromide in the same solvent mixture yields the indoline 8a which structure is proved in a chemical way by conversion of the product into the aldehyde 8d. The different reaction pathway is discussed in terms of steric hindrance by the ester groups. Treatment of 6 with trifluoroacetic anhydride gives the trifluoroacetylated compound 11. Removal of the sterically hindered ester groups in 6, with acetic acid in quinoline at 200°, is accompanied by the simultaneous decarboxylation to yield the pyrrolo[1,2-a]indole 13

Pomeranz-Fritsch cyclisations are reported using a new reagent boron trifluoride-trifluoroacetic anhydride. Isoquinolines carrying 7-OMe groups have been prepared in good yields and the method extended to the formation of N-substituted indoles and of benzthiophen from the corresponding acetals. Benzofuran could not be obtained by this procedure nor could a Bischler-Napieralski type cyclisation be induced. In the latter case the aromatic ring of the starting amide was acetylated when suitably activated.

Study of the racemization of α-phenyl butyric acid in the (CF3CO)2O-CF3CO2H system, indicates that loss of optical activity occurs at the α-phenyl butyric trifluoroacetic mixed anhydride formed in these systems. Kinetic results indicate bifunctional catalysis and the structure of the intermediate complex [mixed anhydride, trifluoroacetic] is discussed.

Lichen depsides have now been synthesized by making use of two reagents, dicyclohexyl-carbodiimide (DCC) and trifluoroacetic anhydride. Methyl evernate, methyl lecanorate and evernic acid have been prepared in satisfactory yields. Altranorin has been synthesized for the first time.

Resume The reaction of trifluoroacetic anhydride on the N-oxide derived from N-methyl 5α-dihydroparavallarine 6 , leads to the immoniums 8 and 9 which can respectively be hydrolysed to furnish the ketone 2 and the secondary amine 1 , and hydrogenated to a mixture of amines 6 and 7 . This reaction has been studied with the help of NMR spectrography and the presence of an unstable intermediate 3 ′ proved.

The relative rates for the reaction of thiophene (1), selenophene (6·5), furan (1·4 × 10 2 ) and pyrrole (5·3 × 10 7 ) with trifluoroacetic anhydride at 75° in 1,2-dichloroethane have been determined using a competitive procedure.