Alkyl trifluoroacetates

Partial anodic oxidation of n-alkanes on a smooth Pt electrode in CF3COOH gives isomeric sec-alkyl trifluoroacetates in 50-80% yield.118... 

Oxalate and trifluoroacetate esters are reactive compounds, which are hydrolyzed in aqueous acid at rates which are not a great deal faster than the rates in neutral solution. Moffat and Hunt170, for example, studied the hydrolysis of a series of alkyl trifluoroacetates in 70% acetone-water, and found that the... 

These are best regarded as SN1 reactions, in which the leaving group is the carboxylate anion. The point is brought out very well by Moffat and Hunt s comparison79 of the solvolyses of /-alkyl trifluoroacetates in 70% aqueous acetone with the reactions of the corresponding /-alkyl halides (Table 26). The activation parameters, and the fate of the carbonium ion, as measured by the percentage of olefin formed by the parallel El reaction, are closely similar for the two types of substrate. 

The important generalizations which can be drawn from the data in Table 27 are that the entropy of activation is typically in or close to the region — 40 to — 50 eu, and that changes in reactivity due to substituents appear primarily in the enthalpy term. AS is particularly low for alkyl trifluoroacetates, and partially compensates, as so often, for particularly low values of A//. The rates of these reactions can be accounted for by a combination of polar and steric effects, and will not be discussed in detail. 

Reactions of this type are relatively few, in comparison to those of DIB. Alkyl benzyl ethers afforded benzaldehyde and alkyl trifluoroacetates in a potentially useful reaction for the deprotection of benzylated alcohols under oxidative conditions, since trifluoroacetates are hydrolysed very easily [53] ... 

Lead(IV)277 and silver(III)301 trifluoroacetates in TFA also oxidize alkanes at room temperature to give alkyl trifluoroacetates [see also Section III.D.3 for reactions of alkanes with Pd(II) trifluoroacetate]. The stoichiometric oxidation of cyclohexane to a mixture of cyclohexanol, cyclohexanone, and adipic acid by cobalt(III) perchlorate in aqueous acetonitrile has also been reported.240... 

Oxyfunctionalization of unactivated C-H bonds. 2,2,3,3-Tetramethylbutane affords a primary alkyl trifluoroacetate in 99% yield when it is oxidized with MefCFjlCOj in the presence of (CFjC0)20 in dichloromethane at 0°. Esters show a remarkable regioselectivity in their oxidation. ... 

A -(2 2-Diethoxyethyl)anilines are potential precursors of 2,3-unsubstituted indoles. A fair yield of 1-methylindole was obtained by cyclization of N-inethyl-M-(2,2-diethoxyethyl)aniline with BFj, but the procedure failed for indole itself[2], Nordlander and co-workers alkylated anilines with bromo-acetaldehyde diethyl acetal and then converted the products to N-trifliioro-acetyl derivatives[3]. These could be cyclized to l-(trifluoroacetyl)indoles in a mixture of trifluoroacetic acid and trifluoroacetic anhydride. Sundberg and... 

Fluoroalkjiations are frequentiy performed indirectly using tandem reactions. Arenes react with sodium borohydride in trifluoroacetic acid to afford otherwise difficult to obtain l,l,l-trifluoro-2,2-diarylethanes. Presumably sodium borohydride reacts initially with the trifluoroacetic acid to produce the trifluoroacetaldehyde or its equivalent, which rapidly undergoes Friedel-Crafts-type condensation to give an intermediate carbinol. The carbinol further alkylates ben2ene under the reaction conditions giving the observed product. The reaction with stericaHy crowded arenes such as mesitylene and durene... 

Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

Alkyl substituents. The steric effect of 1-alkyl substituents in the pyrrole series has been demonstrated in, for example, Vilsmeier formylation reactions. Thus as the bulk of the alkyl substituent on nitrogen is increased e.g. from Me to Bu ) so does the proportion of /3 substitution (70JCS(C)2573). A similar trend has been observed in a series of experiments on the trifiuoroacetylation of A-alkylpyrroles with trifluoroacetic anhydride (80JCR(S)42). 

An interesting case of ipso intramolecular alkylation has been observed in the case of the acid-promoted cyclization of the amino alcohols (61). With trifluoroacetic acid the major product was the rearranged thienopyridine (62), whereas with polyphosphoric acid the product formed exclusively was the non-rearranged thienopyridine (63) (82CC793). 

The change of mechanism with tertiary alkyl esters is valuable in synthetic methodology because it permits certain esters to be hydrolyzed very selectively. The usual situation involves the use of t-butyl esters, which can be cleaved to carboxylic acids by action of acids such as p-toluenesulfonic acid or trifluoroacetic acid under anhydrous conditions where other esters are stable. 

Conversely, when A-alkyl tryptophan methyl esters were condensed with aldehydes, the trans diastereomers were observed as the major products." X-ray-crystal structures of 1,2,3-trisubstituted tetrahydro-P-carbolines revealed that the Cl substituent preferentially adopted a pseudo-axial position, forcing the C3 substituent into a pseudo-equatorial orientation to give the kinetically and thermodynamically preferred trans isomer." As the steric size of the Cl and N2 substituents increased, the selectivity for the trans isomer became greater. A-alkyl-L-tryptophan methyl ester 42 was condensed with various aliphatic aldehydes in the presence of trifluoroacetic acid to give predominantly the trans isomers. ... 

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. 

In recent years the applicability of the Schmidt reaction for the synthesis of more complex molecules—especially the variant employing alkyl azides—has been further investigated. Cycloketones bearing an azidoalkyl side-chain at the a-carbon center have been shown to undergo, upon treatment with trifluoroacetic... 

In an alternate synthesis of the intermediate ketone, the benzylic halide, 69, is used to alkylate sodium phenoxide. Cyclization of the acid (70) obtained on hydrolysis of the ester by means of trifluoroacetic anhydride again gives 67... 

The aqua ion as a ligand is discussed in section 4.5. Silver forms a range of light-sensitive, insoluble carboxylates that find application in the synthesis of, for example, alkyl halides and esters. The benzoate, trifluoroacetate and perfluorobutyrate have dimeric structures others are polymers (Figure 4.6). 

Cationic polymerization of cyclosiloxanes is well known but used much less frequently than anionic reactions. The most widely used catalysts include sulfuric acid and its derivatives, alkyl and aryl sulfonic acids and trifluoroacetic acid1 2,1221. Due to their ease of removal, in industrial applications acid catalysts are generally employed on supports such as bentonite clay or Fuller s earth. 

In methylenechloride/trifluoroacetic acid or fluorsulfonic acid trifluoracetoxyl-ation (Eq. 44) [353] or fluorsulfonation[354] of the alkyl chain remote from the proton-ated carboxyl group occurs. 

Successive groups are replaced with increasing difficulty. Vinyl groups are replaced more readily than saturated alkyl groups, and, with trifluoroacetic acid, two vinyl groups are displaced exothermically at room temperature, and a third after several hours of heating... 

RNH2 (R=alkyl, but not aryl) are phenyliodosyl bis(trifluoroacetate), Phl(0-C0CF3)2 and hydroxy(tosyloxy)iodobenzene, PhI(OH)OTs. A mixture of NBS, Hg(OAc)2, and R OH is one of several reagent mixtures that convert an amide (RCONH2) to the carbamate (RNHCOOR ) (R=primary, secondary, or tertiary... 

B. Reactions.—(/) Halides. Whereas ylides are alkylated in the normal way on treatment with a-bromo- or a-iodo-esters, quite different reactions occur with a-fluoro- and a-chloro-acetates. When salt-free ylides were refluxed in benzene with ethyl fluoroacetate or trifluoroacetate normal Wittig olefin synthesis took place with the carbonyls of the ester groups to give vinyl ethers, e.g. (14). On the other hand, methyl chloroacetate with... 

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