Trifluoroacetic acid catalysis with

Trimethylsilylation is adversely affected by moisture, and therefore, hydrolyzates should be evaporated to dryness as completely as possible. If trimethylsilylation is catalyzed by trifluoroacetic acid, instead of chlorotrimethylsilane, moderate proportions of water may be tolerated,117,127-129 but, even under these conditions, extra peaks may be obtained from partly trimethylsilylated derivatives.130 Catalysis with trifluoroacetic acid is useful when aqueous aliquots from a reaction are to be trimethylsilylated.131 A further advantage of this method, which has been used in the determination of 1,6-anhydro-jS-D-glucopyranose in corn syrup,132 for cycloamyloses,133 and for a series of malto-oligosaccharides,134 is that ammonium trifluoroacetate is soluble in pyridine. 

The effect of catalysis by trifluoroacetic acid on chlorination in carbon tetrachloride has also been determined272. For 1,2,4,5-tetramethylbenzene, with low concentrations of catalyst, the order in catalyst is three-halves, but for toluene (which requires a higher concentration) the order is mixed three- and five-halves the indication is, therefore, that a minimum of three catalyst monomers (or one monomer and one dimer) are necessary. Since trifluoroacetic acid is very likely to be dimeric in carbon tetrachloride, the concentration of monomer is pro-... 

Cleavage with an ensuing Heck reaction was developed by using the T1 triazene linker [51] (Scheme 6.1.20). On cleavage with trifluoroacetic acid a diazonium ion is first formed this can couple to an added alkene under the action of palladium catalysis. The coupling proceeds well with simple terminal alkenes, styrenes, and di- and even trisubstituted alkenes. The advantage of this process is clearly the possibility of using volatile alkenes (and alkynes) without contamination by any salt or other less volatile by-product, particularly with the use of palladium on charcoal as the catalyst. 

A spiroketal is also obtained in low stereoselectivity by addition of a hydroxy group to the double bond of a pyrone with acidic catalysis. Thus, treatment of 3 with 4-methylbenzenesulfonic acid in tetrahydrofuran/water at 65 C for 2 hours, and then with trifluoroacetic acid in benzene at 20 °C, gives a good yield of the corresponding spiroketals in a 67 33 diastereomeric mixture ". 

Chen and coworkers have reported a new domino Michael-Michael addition reaction between a,a-dicyanoalkene [26] derived from cyclohexanone and benzyli-deneacetone, resulting in a stepwise [4 + 2]-type cycloaddition to afford almost enantiopure bicyclic adduct 15. In contrast to the completely inert function of secondary ammonium salt, a primary amine, 9-amino-9-deoxyepiquinine lo [27], in combination with trifluoroacetic acid, was found to be highly efficient in the activation of the a, 3-unsaturated ketone by tandem iminium-enamine catalysis (Scheme 10.21) [28],... 

Stereoselectivity in the condensation reaction of 2-arylethylamines with carbonyl compounds to give 1,2,3,4-tetrahydroisoquinoline derivatives was somewhat dependent on whether acid catalysis or superacid catalysis was invoked. Particularly in the cases of 2-alkyl-N-benzylidene-2-phenethylamines, an enhanced stereoselectivity was observed with trifluorosulfonic acid (TFSA) as compared with the weaker acid, trifluoroacetic acid (TFA). Compound 43 was cyclized in the presence of TFA to give modest to good transicis product ratios. The analogous compound 44 was cyclized in the presence of TFSA to give slightly improved transicis product ratios. 

The use of trifluoroacetic acid has the additional advantage that the formed ester can easily be removed from the reaction mixture by distillation due to the difference in boiling point between the acid and the ester. After hydrolysis, the recovered acid together with unreacted methane can be transferred back into the reactor, the catalysis could be run as a cycHc process. 

The selective oxidation of C—H bonds in alkanes under mild conditions continues to attract interest from researchers. A new procedure based upon mild generation of perfluoroalkyl radicals from their corresponding anhydrides with either H2O2, m-CPBA, AIBN, or PbEt4 has been described. Oxidation of ethane under the reported conditions furnishes propionic acid and other fluorinated products.79 While some previously reported methods have involved metal-mediated functionalization of alkanes using trifluoroacetic acid/anhydride as solvent, these latter results indicate that the solvent itself without metal catalysis can react as an oxidant. As a consequence, results of these metal-mediated reactions should be treated with caution. The absolute rate constants for H-abstraction from BU3 SnH by perfluorinated w-alkyl radicals have been measured and the trends were found to be qualitatively similar to that of their addition reactions to alkenes.80 a,a-Difluorinated radicals were found to have enhanced reactivities and this was explained as being due to their pyramidal nature while multifluorinated radicals were more reactive still, owing to their electrophilic nature.80... 

On the basis of theoretical studies by Bach and co-workers,17 it was found that the nucleophilic 71-bond of the alkene attacks the 0-0 cr-bond in an Sn2 fashion with displacement of a neutral carboxylic acid. There are, however, some mechanistic anomalies. For example, a protonated peracid should be a much more effective oxygen transfer agent over its neutral counterpart, but experiments have shown only modest rate enhancements for acid catalysed epoxidation. Early attempts to effect acid catalysis in alkene epoxidation where relatively weak acids such as benzoic acid were employed proved unsuccessful.18 The picture is further complicated by contradictory data concerning the influence of addition of acids on epoxidation rates.19 Trichloroacetic acid catalyses the rate of epoxidation of stilbene with perbenzoic acid, but retards the rate of a double bond containing an ester constituent such as ethyl crotonate.20 Recent work has shown that a seven-fold increase in the rate of epoxidation of Z-cyclooctene with m-chloroperbenzoic acid is observed upon addition of the catalyst trifluoroacetic acid.21 Kinetic and theoretical studies suggest that the rate increase is due to complexation of the peroxy acid with the undissociated acid catalyst (HA) rather than protonation of the peroxy acid. Ab initio calculations have shown that the free energy of ethylene with peroxy-formic acid is lowered by about 3 kcal mol-1 upon complexation with the catalyst.21... 

The illustration of the process is provided in Figure 2.30.13d At first, pre-rotaxane 82 was generated in a manner similar to that of Figure 2.25. The prerotaxane was subsequently combined with 4,4/-dimethyl-3,3/-dihexyl-2,2/-dipyrrylmethane 83 (10 equiv), and 3,5-di-ter -butylbenzaldehyde 84 (8 equiv) using trifluoroacetic acid catalysis, followed by oxidation of the porphyrinogen intermediates with chloranil 85 to afford bis-copper(I)-complexed [3]-rotaxane 86 in 35% yield. Remarkably, a copper(I)-complexed [5]-rotaxane (87) could be isolated from the reaction mixture in 8% yield. 

During a synthesis of the protein kinase C inhibitor Balanol. Lampe and co-workers77 found that deprotection of the tert-butyl ester 30.1 [Scheme 6.30] with trifluoroacetic or formic acid was accompanied by substantial quantities of a debenzylated by-product. The same side reaction accompanied thermolytic cleavage of the terf butyl ester in neutral solvents presumably due to add catalysis by the carboxylic acid product 30.2. Thermolysis in quinoline at 205 °C led cleanly to the desired benzophenone carboxylic acid 30.2 in 68% yield. 

The use of Lewis acid catalysis is a powerful method of increasing the rates and diastereoselectivity of many IMDA reactions. Several examples involving terminally activated nona- and deca-trienes are summarized in Tables 1 and 2. Examples illustrating rate and stereoselectivity improvements in the cycliza-tions of functionalized decatrien-3-ones appear in Figure 5. The most striking of these is the cyclization of (12) when performed in the presence of trifluoroacetic acid at -78 "C, providing (13) with 94% stereoselectivity. ... 

Nitroethene is sufficiently electrophilic to substitute indole without the need for acid catalysis. Despite this, it has been shown that siUca-gel-supported CeCl3.7H20/NaI brings about such reactions at room temperature under solvent-free conditions or, to take another solvent extreme, the reaction occurs in water with a catalytic amount of a heteropoly acid (H3PWi204o). The employment of 2-dimethylamino-l-nitroethene in trifluoroacetic acid leads to 2-(indol-3-yl)nitroethene - the reactive species is the protonated enamine and the process is similar to a Mannich condensation (20.1.1.9). The use of 3-trimethylsilyl-indoles, with tpxo-substitution of the silicon, is an alternative means for effecting alkylation, avoiding the need for acid catalysis. 

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