Trifluoroacetate side products

The cyclization of 1,19-dideoxybilene-i-dicarboxylic acid esters has been widely used for the synthesis of porphyrins. In this case, the use of tert-butyl esters which can be hydrolyzed with trifluoroacetic acid prior to the cyclization step is necessary. The cyclization step also requires trifluoroacetic acid and orthoformates. However, attempts to prepare porphyrins with /f-acceptor substituents can give rise to problems with side products and yields. 

Synthesis of a tricyclic core of marine alkaloid variolin B has been achieved in three steps. The key reaction involves tandem deoxygenation and cylization of a triarylmethanol 187 using a combination of trifluoroacetic acid (TFA) and triethylsilane (TES). The use of 4.3equiv of TFA and 8.1 equiv of TES minimizes the formation of side products 188, 189 and allows the formation of the desired product 190 in 34% yield (Scheme 5) <2005JOC6204>. 

Unsymmetrical ethers may be produced from the acid-promoted reactions of aldehydes and organosilicon hydrides when alcohols are introduced into the reaction medium (Eq. 173).327,328 An orthoester can be used in place of the alcohol in this transformation.327 335 A cyclic version of this conversion is reported.336 Treatment of a mixture of benzaldehyde and a 10 mol% excess of triethylsilane with methanol and sulfuric, trifluoroacetic, or trichloroacetic acid produces benzyl methyl ether in 85-87% yields.328 Changing the alcohol to ethanol, 1-propanol, 2-propanol, or 1-heptanol gives the corresponding unsymmetrical benzyl alkyl ethers in 45-87% yield with little or no side products.328 A notable exception is the tertiary alcohol 2-methyl-2-propanol, which requires 24 hours.328 1-Heptanal gives an 87% yield of //-lie ply I methyl ether with added methanol and a 49% yield of benzyl n-heptyl ether with added benzyl alcohol under similar conditions.328... 

Similar treatment of a trifluoroacetic acid solution of p-tolualdehyde with triethylsilane gives only a 20% yield of /7-xylene after 11 hours reaction time followed by basic workup. Use of 2.5 equivalents of dimethylphenylsilane enhances the yield to 52% after only 15 minutes. This reaction proceeds stepwise through the formation of a mixture of the trifluoroacetate and the symmetrical ether. These intermediates slowly form the desired /7-xylene product along with Friedel-Crafts side products under the reaction conditions (Eq. 192).73 Addition of co-solvents such as carbon tetrachloride or nitromethane helps reduce the amount of the Friedel-Crafts side products.73... 

Under certain conditions, the trifluoroacetic acid catalyzed reduction of ketones can result in reductive esterification to form the trifluoroacetate of the alcohol. These reactions are usually accompanied by the formation of side products, which can include the alcohol, alkenes resulting from dehydration, ethers, and methylene compounds from over-reduction.68,70,207,208,313,386 These mixtures may be converted into alcohol products if hydrolysis is employed as part of the reaction workup. An example is the reduction of cyclohexanone to cyclohexanol in 74% yield when treated with a two-fold excess of both trifluoroacetic acid and triethylsilane for 24 hours at 55° and followed by hydrolytic workup (Eq. 205).203... 

Trimethylsilyl-protected 1-isopropenylcyclobutanols were rearranged to cyclohexanones via a two-step reaction sequence.114 The vinylcyclobutanes 1 were first treated with mercury(II) trifluoroacetate. The crude products were then converted into chlorides (which can be isolated) and finally reduced with tributyltin hydride to give 2. Sometimes small amounts of five-mem-bered ring compounds, which are intermediates of this two-step ring enlargement, are formed as side products. 

The disadvantage of the Swern oxidation is the formation of side products from the Pum-merer rearrangement (see section 1.6.1, Scheme 1.26). To avoid the side reactions in the Swern oxidation, the temperature is kept at -78°C, but when trifluoroacetic anhydride instead of oxalyl chloride is used the reaction can be warmed to -30° C. The use of diisopropylamine as a base stops side reactions. 

Although most common carboxylic acids can be used successfully in this context (equation 57), formic acid gives the indole dimer derived side product (21 equation 58) and trifluoroacetic acid gives the condensation product (22 equation 59), ° in addition to the expected products. The particular prob-... 

The chloride formed thereby may react as nucleophile or may be oxidized at the anode to chlorine, which leads to unwanted chlorinated side products. This reductive cleavage can be avoided by addition of strong acids, such as trifluoroacetic acid, methanesulfonic acid, or trifluoromethanesulfonic acid [2], These acids effectively suppress the chlorination, because is reduced at the cathode rather than dichloromethane. However, they also decrease the yield of biaryl products and increase the yield of diphenylmethanes. 

For the oxidation of unsubstituted 1-aminopyrazole, the highest yield (46%) of 1,2,3-triazine is obtained with sodium periodate, which also provides high yields (82-93%) for other triazines (89H1809). 1,2,3-Triazine can be obtained in 20% yield on oxidation of N-aminopyrazole with nickel peroxide or lead dioxide in methylene chloride in the presence of acetic or trifluoroacetic acid (85JOC5520, 85LA1732) however, these results are not always reproduceable [86JCS(P1 )1249], As side products, cis- and zra/i.s-isomers of N./V -azopyrazoles are often isolated in yields of 35-45%. 

Another resin-capture approach has been pubhshed in relation to the synthesis of tetrasubstituted ethylenes via Suzuki coupling reactions (Scheme 20) [42, 53]. A 25-member hbrary was synthesized using five alkynes, five aryl halides, and a polymer-bound aryl iodide. The alkynes 55 were converted into bis(boryl)alkenes 56 in solution, and the crude intermediates were used in Suzuki reactions with an excess of aryl halide. When all of the bis(boryl)alkene 56 had been consumed, the aryl iodide resin 59 was added to the reaction mixture and the reaction continued on the solid support. Side products such as 58, arising from a double Suzuki reaction, remained in solution and could be washed away. Compounds 60 were cleaved from the polymer using trifluoroacetic acid and products 61 were obtained in > 90% purity. 

Oximes were cleaved by tetraphenylbismuthonium trifluoroacetate under basic conditions to regenerate the ketone, but stable O-triphenylbismuth bisoximates were obtained from the reaction of an oxime with triphenylbismuth dichloride under basic conditions.59 Imides were phenylated in moderate yields by tetraphenylbismuthonium trifluoroacetate. In the reaction of indole with tetraphenylbismuthonium trifluoroacetate under neutral conditions, 3,A diphenylindole was isolated as a very minor side product (2%).33... 

Arylthallium bis(trifluoroacetate)s are converted by successive treatment with KF and BF3 into aryl fluorides.Thallium(iii) nitrate (TTN) readily oxidizes dialkyl sulphides and selenides to the corresponding sulphoxides or selenoxides, and 2-(alkylthio)-l-arylethanones (37) into compounds (38) in methanolic solution.In a modification of the TTN oxidative conversion of aryl alkyl ketones into arylacetic acids, enol ethers derived from the ketones are used instead of the ketones themselves. This reduces the formation of side products. Cyclic aralkyl ketones (39) may be ring-expanded and alkylated to give compounds (40) via treatment of their Wittig-derived alkenes with TTN/ an extrapolation of the basic reaction discovered previously. 

Furthermore, the oxidizing strength of fluorine can lead to the formation of side products. To reduce side reactions, the reactivity of [ F]p2 is moderated by dilution with inert gas (neon) at low temperatures (Casella et al. 1980). The solvent has to be inert as well. Freon, trifluoroacetic acid, carbon tetrachloride, and hydrogen fluoride are used. 

Trifluroroacetates (100) are prepared by dissolving the bile acid methyl ester (o> the partial silyl ether) in trifluoroacetic anhydride, 15 min, 35 °C (101). The reagent is removed under a stream of nitrogen. Milder conditions yield partial derivatives. Enol esters of 3-keto-J- bile acids may be formed as side products. Trifluoroacetates should be analyzed within 1-2 days since signs of decomposition may appear on storgae for more than 48 hr at room temperature (7, 102). 

Rathke and coworkers found that combining this bulky alkoxide again with trifluoroacetic acid leads to a highly efficient catalytic system for the Oppenauer oxidation. For instance, cyclohexanol could be oxidised, at 0 °C within a couple of minutes, to give cyclohexanone in 88% yield, in the presence of 5 mol% of aluminium tri-tert-butoxide activated with 2.5 mol% of trifluoroacetic acid as shown in Scheme 18.5. However, the control provided by this catalytic system in the MPV/Oppenauer reactions leaves some room for improvement and the aluminium-catalysed formation of side products via concurrent aldol reactions (Scheme 18.2) could be observed when enolisable substrates were used. ... 

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