Boron trifluoride-Trifluoroacetic

A number of Lewis acids have been utilized in the Pomeranz-Fritsch reaction, including polyphosphoric acid and boron trifluoride-trifluoroacetic anhydride. Under the latter conditions yields were best when electron-donating groups were present in the 3- or 3, 4- position of imine 20, whereas unactivated aldehydes failed to cyclise at all. ... 

The hydrogen fluoride catalyzed fluorination of norbornene by xenon difluoride at room temperature leads to a mixture of at least seven components,39 but under milder conditions (— 78 to 26 C, 22 hours) the reaction affords a mixture of two main products 2-e,xo-5-cxo-difluoro-norbornane and 2-c-wfo-5- Yo-difluoronorbornane, ratio 2 1, in a total yield of 51-76%. If the same reaction is carried out in a limited temperature range between — 46 and — 39 C the yield of these products decreases, their ratio becomes equal, and the main product is 2-exo-l-ff //-difluoronorbornane (42 %).40 The structure dependence of the fluorination products of norbornene with xenon difluoride was studied. Solvent, temperature, reaction duration, catalyst (hydrogen fluoride, boron trifluoride, trifluoroacetic acid, pentafluorobenzenethiol) and the routes of product isomerization were analyzed.41-42... 

The Pomeranz-Fritsch method (boron trifluoride + trifluoroacetic anhydride) is not suitable 205 but polyphosphoric acid (PPA) at 100°... 

In the past decade, there has appeared only one report, which can be classified under this heading, on the monodeoxygenation of spiro-adamantane-l,2-dioxetanes induced by catalytic amounts of tris-(2,4-dibromophenyl)-aminium hexachloroantimonate <1998T6939>. An electron-transfer mechanism from the aminium salt has been proposed for the observed formation of various ketones. Reports citing the electrophilic ring opening of dioxetanes by boron trifluoride, trifluoroacetic acid, and various other Lewis acids have been summarized in CHEC-II(1996) <1996CHEC-II(1B)1041>. 

It has long been apparent that when the acid concentration is too low, the Schiff base is hydrolyzed back to its components and, when it is too high, extensive decomposition results. In order to obviate the decomposition problem, numerous acidic reagents have been tried. Some of these are polyphosphoric acid-phosphorus oxychloride,2 polyphosphoric acid,8 and boron trifluoride-trifluoroacetic anhydride.8 Some improvement has been observed, but many yields are still poor. 

POMERANZ-FRITSCH REACTION Boron trifluoride-Trifluoroacetic anhydride. 

One of the methylthio groups of a ketenedithioacetal is displaced by an anion derived from an active methylene group simultaneously, the other MeS and R (an activating group) are eliminated. A Pomeranz-Fritsch reaction, catalysed by boron trifluoride-trifluoroacetic anhydride (see also Section II. 1), is an attractive synthesis of some l-alkyl-2,3-unsubstituted indoles. Recent work on indoles has been reviewed [3893]. 

Cations like that present in (iv) exist in solutions of aromatic hydrocarbons in trifluoroacetic acid containing boron trifluoride, and in liquid hydrogen fluoride containing boron trifluoride. Sulphuric acid is able to protonate anthracene at a mero-position to give a similar cation. ... 

Methane sulfonic acid, trifluoroacetic acid, hydrogen iodide, and other Brmnsted acids can faciUtate 3 -acetoxy displacement (87,173). Displacement yields can also be enhanced by the addition of inorganic salts such as potassium thiocyanate and potassium iodide (174). Because initial displacement of the acetoxy by the added salt does not appear to occur, the role of these added salts is not clear. Under nonaqueous conditions, boron trifluoride complexes of ethers, alcohols, and acids also faciUtate displacement (87,175). 

The 5-isobutoxymethyl monothioacetal is stable io2N hydrochloric acid and to 50% acetic acid some decomposition occurs in 2 A sodium hydroxide. The monothioacetal is also stable to 12 A hydrochloric acid in acetone (used to remove an A -triphenylmethyl group) and to hydrazine hydrate in refluxing ethanol (used to cleave an A-phthaloyl group). It is cleaved by boron trifluoride etherate in acetic acid, by silver nitrate in ethanol, and by trifluoroacetic acid. The monothioacetal is oxidized to a disulfide by thiocyanogen, (SCN)2. ... 

Treatment of the indole derivative 290 with trifluoroacetic acid gave the addition product 291 that upon cyclization afforded the pyridoindole derivative 292 (81H713). Treatment of 290 which has a dioxopiperazine ring on C-3 with boron trifluoride etherate gave a mixture of pyrroloindole 293... 

Hlasta and Deng have developed a two-step solid-phase method for the decoration of azoles at C-2 [188]. First, imidazole was loaded onto a polystyrene-bound carbamyl chloride via a benzaldehyde bridge (Fig. 40). The 2-substi-tuted imidazole was efficiently cleaved in good yields in the presence of various nucleophiles (i.e., water, alcohols, and amines), trifluoroacetic acid, and boron trifluoride under microwave irradiation in a closed vessel at 120 °C for 5 min. 

Thallium(III), particularly as the trifluoroacetate salt, is also a reactive electrophilic metallating species, and a variety of synthetic schemes based on arylthallium intermediates have been devised.75 Arylthallium compounds are converted to chlorides or bromides by reaction with the appropriate cupric halide.76 Reaction with potassium iodide gives aryl iodides.77 Fluorides are prepared by successive treatment with potassium fluoride and boron trifluoride.78 Procedures for converting arylthallium compounds to nitriles and phenols have also been described.79... 

Secondary Alkyl Alcohols. Treatment of secondary alkyl alcohols with tri-fluoroacetic acid and organosilicon hydrides results only in the formation of the trifluoroacetate esters no reduction is reported to occur.1,2 Reduction of secondary alkyl alcohols does take place when very strong Lewis acids such as boron trifluoride126 129 or aluminum chloride136,146 are used. For example, treatment of a dichlo-romethane solution of 2-adamantanol and triethy lsilane (1.3 equivalents) with boron trifluoride gas at room temperature for 15 minutes gives upon workup a 98% yield of the hydrocarbon adamantane along with fluorotriethylsilane (Eq. 10).129... 

Benzyl Alcohols. Benzyl alcohols of nearly all kinds undergo reduction when treated with acid in the presence of organosilicon hydrides. The most obvious exception to this is the behavior of benzyl alcohol itself. It resists reduction by the action of trifluoroacetic acid and triethylsilane, even after extended reaction times.26 Reducing systems consisting of triethylsilane and sulfuric acid/acetic acid or p-toluenesullonic acid/acetic acid mixtures also fail to reduce benzyl alcohol to toluene.134 As previously mentioned, substitution of boron trifluoride for trifluoroacetic acid results in the formation of modest yields of toluene, but only when a very large excess of the silane is used in order to capture the benzyl cation intermediate and suppress Friedel-Crafts oligomerization processes.129,143... 

An example of an alcohol that can undergo rapid skeletal rearrangement is 3,3-dimethyl-2-phenyl-2-butanol (Eq. 29). Attempts to reduce this alcohol in dichloromethane solution with l-naphthyl(phenyl)methylsilane yield only a mixture of the rearranged elimination products 3,3-dimethyl-2-phenyl-l-butene and 2,3-dimethy 1-3-phenyl-1 -butene when trifluoroacetic acid or methanesulfonic acid is used. Use of a 1 1 triflic acid/triflic anhydride mixture with a 50 mol% excess of the silane gives good yields of the unrearranged reduction product 3,3-dimethyl-2-phenylbutane, but also causes extensive decomposition of the silane.126 In contrast, introduction of boron trifluoride gas into a dichloromethane solution of the alcohol and a 10 mol% excess of the silane... 

A variety of para-substituted 2-phenyl-2-butanols undergo quick and efficient reductions to the corresponding 2-phenylbutanes when they are dissolved in dichloromethane and a 2-10% excess of phenylmethylneopentylsilane and boron trifluoride is introduced at 0° (Eq. 30).126 Several reactions deserve mention. For example, when R = CF3, use of trifluoroacetic acid produces no hydrocarbon product, even after two hours of reaction time. In contrast, addition of boron trifluoride catalyst provides an 80% yield of product after only two minutes. When R = MeO, both trifluoroacetic acid and boron trifluoride produce a quantitative yield of the hydrocarbon within two minutes. However, when R = NO2, attempts to promote the reduction with either trifluoroacetic acid or even methanesulfonic acid fail even after reaction periods of up to eight hours, only recovered starting alcohol is obtained. Use of boron trifluoride provides a quantitative conversion into 2-(/ -nitrophenyl)butane after only ten minutes. It is significant that the normally easily reducible nitro group survives these conditions entirely intact.126129 Triethylsilane may be used as the silane.143... 

Acids that are used in addition to trifluoroacetic acid include trifluoroacetic acid with added sulfuric acid203 or boron trifluoride etherate,210,211 perfluorobu-tyric acid,212 hydrogen chloride/aluminum chloride,136,146,213 perchloric acid in chloroform,214 p-loluenesull onic acid alone134 or with aluminum bromide or aluminum chloride,192 concentrated sulfuric acid in two-phase systems with dichloromethane, alcohol, or ether solvents,209,215 trifluoromethanesulfonic acid,216 chlorodifluoroacetic acid,134 and the monohydrate of boron trifluoride... 

The behavior of members of the bicyclo[2.2.1]heptene family is also different from that of other common 1,2-disubstituted alkenes.230 The parent bicy-clo[2.2.1]heptene gives bicyclo[2.2.1]heptane in only 3.5% yield when it is treated with Et3SiH/TFA. The major product is reported to be a 2-bicyclo[2.2.1]heptyl trifluoroacetate of unspecified configuration (Eq. 70).230 The carbocation intermediate is presumably the 2-norbornyl cation. Addition of small amounts of boron trifluoride etherate to the reaction mixture causes the yield of hydrocarbon product to rise to 22% after a reaction time of 24 hours at room temperature. Further... 

Treatment of a pentacyclic la, I I -(2-oxethano) thioketal steroid with excess Et3SiH/TFA causes reduction of the carbon-carbon double bonds as well as the 17-carbonyl group to give a single reaction product (Eq. 213).368 Other work utilizes trifluoroacetic acid, triethylsilane, and anisole in the presence of a catalytic amount of boron trifluoride etherate to reduce the acetyl carbonyl of a 3-acetyl-2-azetidinone derivative with a dr of 8 1 (Eq. 214).395... 

In a similar way, a mixture consisting of 2% boron trifluoride etherate in trifluoroacetic acid and triethylsilane brings about the regioselective reduction of the acyclic carbonyl group of the diketovinyl chloride shown in Eq. 215 in high yield (>94%), but with formation of approximately equal amounts of the two possible diastereomers formed from the creation of a new chiral center.396... 

Thermolysis of 219a and 219b produced the benzofulvenes 221 as expected. However, the formation of 222 from 219c can best be accounted for by regarding the biradical 220a as the carbene 220b to allow an intramolecular C-H insertion reaction. The presence of a carbonyl group in 219 also permits the use of samarium(II) iodide, samarium(III) chloride, boron trifluoride and trifluoroacetic acid to promote the Schmittel cyclization reaction. 

Groves and Swan tried unsuccessfully to cyclize Af-2-(indol-3-yl)ethyl aminomethylenemalonate (1413) to tetrah ydro-/3-carboline-1 -acetate (1414) by the action of an acid or base. Instead of cyclization, hydrolysis of 1413 occurred to yield tryptamine (52JCS650). Later, Maclaren obtained 3,4-dihydro-/3-carboline when he treated 1413 with trifluoroacetic acid or boron trifluoride (87AJC1617). 

The reaction of allyltrimethylsilane with benzenetellurinyl trifluoroacetate, followed by a primary or secondary amine (octylamine, aniline, piperidine, etc.) and boron trifluoride... 

Triethylsilane in the presence of boron trifluoride [772] or trifluoroacetic acid [777] also reduced the aldehyde group to a methyl group. 

Method A A solution of 0.5 mmol of (2/ /S ,3R/S )-2,3-dialkyl-1,4-diarylbutane and 0.125 mL (1.0 mmol) of boron trifluoride-diethyl ether complex in 2 mL of trifluoroacctic acid is added to a suspension of 0.12 g (0.26 mmol) of thallium(III) oxide in 2 mL of trifluoroacetic acid at — 40°C to +25CC under an argon atmosphere. The dark colored solution is stirred until the reaction is complete, diluted with ethyl acetate, then washed successively with water (twice) and sat. aq NaCl. Evaporation of the dried extract gives the crude product. In a variant of this method the boron trifluoride-diethyl ether complex can be omitted. 

Method E To a suspension of 0.67 mM of ruthenium(IV) dioxide dihydrate in 0.8 mL of trifluoroacetic acid, 0.4 mL of trifluoroacetic anhydride, and 4 mL of CH2C12 at 0 C is added, with stirring and under argon, a solution of 0.33 mM of prestegane B in 4mL of CH2C12 and, immediately, 0.2 mL of boron trifluoride-diethyl ether complex. After 3 h. the suspended solid is removed by filtration. Evaporation and flash chromatography affords the pure crystalline product yield 84% mp 228-230°C. 

The ring enlargement of 2,3-divinylcyclobutanones has been catalyzed by boron trifluoride or trifluoroacetic acid.110 This acid catalysis, however, usually gives lower yields than the thermal reaction and favors rearrangement to five- or six-membered rings. 

The introduction of fluorine into activated arenes is achieved by the combination thallium(III) trifluoroacetate/potassium fluoride/ boron trifluoride. Thallium(III) is hereby an oxidative fluo-rinating reagent.910 Representative compounds prepared in this way are listed below. 

Tetrasubstituted 4//-pyrans 153 and 431 were found to disproportionate with trifluoroacetic acid359 and with boron trifluoride-hydrogen bromide reagent360 to mixtures of pyrylium salts 395a,b and tetrahydro-pyrans 432359 or 433,360 respectively. 

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