Acetals trifluoromethanesulfonate

The first member of the series, CF SO H, has been extensively studied. Trifluoromethanesulfonic acid [1493-13-6] is a stable, hydroscopic Hquid which fumes in air. Addition of an equimolar amount of water to the acid results in a stable, distillable monohydrate, mp 34°C, bp 96°C at 0.13 kPa (1 mm Hg) (18). Measurement of conductivity of strong acids in acetic acid has shown the acid to be one of the strongest protic acids known, similar to fluorosulfonic and perchloric acid (19). 

Considerable efforts have been devoted to the stereoselective introduction of a /(-methyl function in intermediates for the synthesis of 1 jS-methylcarbapenems. While the trimethylsilyl trifluoromethanesulfonate catalyzed reaction of a 4-acetoxyazetidinone derivative with ketene acetals shows no selectivity, ketene thioacetals lead to stereoselective formation of the a-methyl isomer108. The zirconium enolate, however, shows high /(-methyl selectivity. 

As an alternative to lithium enolates. silyl enolates or ketene acetals may be used in a complementary route to pentanedioates. The reaction requires Lewis acid catalysis, for example aluminum trifluoromethanesulfonate (modest diastereoselectivity with unsaturated esters)72 74 antimony(V) chloride/tin(II) trifluoromethanesulfonate (predominant formation of anti-adducts with the more reactive a,/5-unsaturated thioesters)75 montmorillonite clay (modest to good yields but poor diastereoselectivity with unsaturated esters)76 or high pressure77. 

High enantioselectivities may be reached using the kinetic controlled Michael addition of achiral tin enolates, prepared in situ, to a,/i-unsaturated carbonyl compounds catalyzed by a chiral amine. The presence of trimethylsilyl trifluoromethanesulfonate as an activator is required in these reactions236. Some typical results, using stoichiometric amounts of chiral amine and various enolates are given below. In the case of the l-(melhylthio)-l-[(trimethylsilyl)thio]ethene it is proposed that metal exchange between the tin(II) trifluoromethanesulfonate and the ketene acetal occurs prior to the 1,4-addition237,395. 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

The addition reactions discussed in Sections 4.1.1 and 4.1.2 are initiated by the interaction of a proton with the alkene. Electron density is drawn toward the proton and this causes nucleophilic attack on the double bond. The role of the electrophile can also be played by metal cations, and the mercuric ion is the electrophile in several synthetically valuable procedures.13 The most commonly used reagent is mercuric acetate, but the trifluoroacetate, trifluoromethanesulfonate, or nitrate salts are more reactive and preferable in some applications. A general mechanism depicts a mercurinium ion as an intermediate.14 Such species can be detected by physical measurements when alkenes react with mercuric ions in nonnucleophilic solvents.15 The cation may be predominantly bridged or open, depending on the structure of the particular alkene. The addition is completed by attack of a nucleophile at the more-substituted carbon. The nucleophilic capture is usually the rate- and product-controlling step.13,16... 

Addition reactions such as A-alkylation do not occur readily, and trimethylsilylmethylation of 3,4-diphenyl-l,2,5-thiadiazole 8 with trimethylsilylmethyl trifluoromethanesulfonate at 80°C occurred at N-2 < 1999J(P1) 1709>. The electron-rich 3-hydroxy-l,2,5-thiadiazole can be preferentially methylated on N-2 using trimethyl orthoacetate in toluene to afford the 2-methyl-l,2,5-thiadiazol-3-one in 69% yield <2002EJ01763>, although a mixture of 3-hydroxythiadiazole and neat trimethyl orthoacetate showed a 20 80 ratio of N- versus 0-alkylation products by H NMR. Treatment of 3-hydroxy-l,2,5-thiadiazole with /-butyl acetate under acid catalysis (Amberlyst 15) gave almost exclusively the A-alkylated compound <2002BMC2259>. 

There are relatively few entries in the non-fused dioxepin area, and most of these focus on reactions of these systems. For example the triflic acid-initiated polymerisation of 1,3-dioxepane in the presence of acetic acid and hexanedicarboxylic acid has been studied and mechanistic aspects discussed <00JPS(A)1232>. Biodegradable microspheres for the controlled delivery of drugs have been made from copolymers and homopolymer blends of L-lactide and l,5-dioxepan-2-one <00PP1628>. Ring contraction of 5-methylene-l,3-dioxepanes (eg. Ill) on reaction with trimethylsilyl trifluoromethanesulfonate in the presence of base afforded the exo tetrahydropyrans, in good yields <00TL2171>. 

A diastereoselective synthesis of /3-(iV-acylamino)aldehydes was accomplished via ruthenium-catalyzed isomerization of 0-vinyl-iV,0-acetals followed by rearrangement in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) (Scheme 36).63... 

The Schiff base derivatives 73 of the 3-hetaryl-substituted 4-amino-3-thiol-l,2,4-triazoles, on treatment with acetic anhydride, undergo cyclization to give the corresponding 3-substituted-5-acetyl-5,6-dihydro-6-phenyl[l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 76 (Equation 16) <1990IJB135>. Similar treatment of 4-(A-bcnzoylamino)-4,5-dihydro-l-methyl-3-mcthylthio-1 //-[ 1,2,4 triazolc-5-thione 77 leads to the [l,2,4]triazolo[3,4-4][l,3,4]thiadiazolium trifluoromethanesulfonate 78 (Equation 17) <1986LA1540>. 

To avoid the above mentioned problems, diazonium salts were synthesized by diazotizing amino compounds with isopentyl nitrite in acetic acid containing a strong acid such as trifluoromethanesulfonic acid. After completion of... 

Table 1 summarizes the results of the reactions of ynoates (2a-c) with a silicon enolate (silyl ketene acetal) and a lithium enolate of methyl propionate (Eq. 1). Except for the reaction of 2c, Fe-Mont catalyzed exclusive 1,2-addition of silyl ketene acetal to 2a and 2b to give an adduct of 3 in high yields. However, even trimethyl silyl trifluoromethanesulfonate (TMSOTf), a generally applied homogeneous strong acid, failed to effect the addition reaction. 

Pyrazinyl ketones can be protected as the acetal by treatment with alkanediol in the presence of trifluoromethanesulfonic acid <1999JA8783> or 8-amino-l,3,6-pyrenetrisulfonic acid (APTS) <2005JOC2616>. 

A non-aqueous method for the titration of procaine and other drugs using trifluoromethanesulfonic acid was reported by Zakhari and Kovar [88]. Solutions of procaine hydrochloride in anhydrous acetic acid, acetic anhydride, their mixture, or in acetone, was titrated with an acetic acid solution of 0.1 M trifluoromethanesulphonic acid or 0.1 M perchloric acid. Titration was effected in the presence or in the absence of mercurous acetate. The end point was detected visually (using crystal violet as indicator) or potentiometrically. 

A special case is the ring-forming reaction in the lactone acetal 568,69. When 5 is treated with trimethylsilyl trifluoromethanesulfonate (trimethylsilyl triflate TMSOTf) in the presence of triethylamine at 0°C the cisjtrans mixture 6a and 6b is formed in ca. 50% yield. In this intramolecular aldol reaction the probable intermediate is the oxonium ion 7. 

A mixture of 1 (100 mg, 0.2 mmol) and ammonium trifluoromethanesulfonate (377 mg, 2.2 mmol) in THE (10 mL) was reacted with NaBH(OEh)3 (2 equiv) at room temperature under an argon atmosphere. The reaction was monitored by TLC analysis. After the reaction was complete, the solvent was removed by a rotary evaporator, the mixture extracted with ethyl acetate, dried over anhydrous Na2S04, and concentrated. 

A mixture consisting of the step 1 product (4.7 mmol), 4-(2-pyridyl) benzaldehyde (9.3 mmol), and 500 ml of toluene was stirred at ambient temperature for several hours and then treated with silver trifluoromethanesulfonate (9.3 mmol). The mixture refluxed for 3 hours and was then cooled to ambient temperature and filtered through Celite and then concentrated. The residue was purified by silica gel column chromatography using chloroform/ethyl acetate, 19 1, respectively, and then recrystallized in CH2CI2/methanol and 0.95 g of product isolated. 

F,MnO SC6, Manganese( I), pentacarbonyl-(trifluoromethanesulfonato)-, 26 114 F,0 CH, Acetic acid, trifluoro-tungsten complex, 26 222 F,02C,H, Acetic acid, trifluoro-ruthenium complex, 26 254 FjOjSCH, Methanesulfonic acid, trifluoro-iridium, manganese and rhenium complexes, 26 114, 115, 120 platinum complex, 26 126 F304PtSC,4H,5, Platinum(II), hydrido-(methanol)bis(triethylphosphine)-Irans-, trifluoromethanesulfonate,... 

Acetic acid, trifluoro-, anhydride with trifluoromethanesulfonic acid)... 

All these electrolytes are neutral in Bronsted acid-base properties. Although rather exceptional, an acid, a base, or a pH buffer may be added to the supporting electrolyte of neutral salts. The acid-base system to be selected depends on the purpose of the measurement. We often use trifluoromethanesulfonic acid (CF3S03F1) as a strong acid acetic acid, benzoic acid, or phenol as a weak acid an amine or pyridine as a weak base and tetraalkylammonium hydroxide (ILtNOH) as a strong base. Examples of buffer systems are the mixtures of picric acid and its R4N-salt and amines and their PlCl04-salts. Here, we should note that the acid-base reactions in aprotic solvents considerably differ from those in water, as discussed in Chapter 3. 

R)-(+)-2-Hydroxy-1,2,2-triphenylethyl acetate [(R)-HYTRA], To a mechanically stirred solution of (R)-(+)-1,1,2-triphenyl-1,2-ethanediol (35.0 g. 0.121 mol, Note 1) and acetic anhydride (17.1 mL, 0.181 mol, 1.5 eq, Note 2) in anhydrous acetonitrile (500 mL, Note 3) at room temperature under nitrogen is added a solution of scandium(lll) trifluoromethanesulfonate (1.23 g, 2.5 mmol, 2 mol%, Note 4) in anhydrous acetonitrile (125 mL) over approximately 35 min (Note 5). After about 8 min a white precipitate begins to appear, and the resulting mixture is stirred at room temperature under nitrogen for a total of 3 hr. The solid is filtered, washed with acetonitrile (2 x 25 mL), and dried under vacuum at 40°C overnight to afford (R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate (35.42 g, 0.107 mol, 88%) as a white solid (Note 6). 

TLC analysis on Silica Gel 60F-254 plates eluting with cyclohexane-ethyl acetate (7 3) showed the clean formation of product with Rf = 0.69, at the expense of the starting material with Rt = 0.3. If a small amount of starting material was still present at this time, more tert-butyldimethylsilyl trifluoromethanesulfonate (0.22 mL, 0.95 mmol) and 0.2 mL of triethylamine were added and the reaction mixture was stirred for a further 30 min, at which time the TLC analysis generally showed the reaction to be complete. 

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