Acylation, with acyl trifluoroacetates

In an interesting analogy to the penicillin series, acylation of 7-ACA with the phenylglycine moiety affords a compound with oral activity. Thus, phenylglycine is first protected as the carbo tertiary butyloxy derivative (45). Reaction of this with isobutyloxy chloroformate affords the mixed anhydride (46). Condensation of that with 7-ACA gives the intermediate, 47. Treatment with either trifluoroacetic or formic acid provides the free amine cephaloglycin (48). ... 

Rice and Nuss report that the Argopore MB-CHO polymer-supported amidoximes 282 (readily available from the nitrile 281), shown in Scheme 46, can be acylated with acid chlorides in the presence of excess pyridine to give the O-acylamidoximes 283. Cyclization was carried out with TBAF in THF at ambient temperature, to give the polymer-supported 1,2,4-oxadiazoles 284. Release of the 1,2,4-oxadiazoles 285 from the polymer support was achieved by treatment with 95% trifluoroacetic acid <2001BML753>. 

Figure 2.43 Acylation reactions with ethyl trifluoroacetate.

Both the experimental and calculated equilibrium constants indicate the great thermodynamic instability of hemiorthoesters with respect to the corresponding esters and show why it is normally impossible to detect the tetrahedral intermediates in acyl-transfer reactions. On going from intermolecular to intramolecular reactions the tetrahedral intermediate becomes relatively more stable, and if the structure is more rigid (cf. [120], [121] in Table 17) or more sterically crowded (cf. [119]) the tetrahedral intermediate is more stable still. However, it is only with structues as rigid as tetrodotoxin or with the trifluoroacetate of pinacol that the hemiorthoester is more stable than the ester (see Section 1). ... 

Roberts and Wells354 were the first to use triflic acid in the acylation of phospha-ferrocenes with acetic anhydride and benzoic anhydride to afford ketophosphaferro-cenes in good yields (62-78%). Recently, acyl trifluoroacetates in excess triflic acid have been shown to be even more effective reagents355 [Eq. (5.141)]. 

DIB, BTI and perfluoro-DIB were suitable precursors the last was most effective under photochemical conditions, whereas DIB and BTI were used either thermally or photochemically for DIB, best results were obtained with added trifluoroacetic acid, photochemically. Not only alkyl but other more complex free radicals could also be introduced, notably acyl radicals. Products derived from acids bearing sugar moieties were obtained in low to moderate yield. In the case of acetonides complete retention of the initial configuration was observed. This high diastereoselectivity... 

Acylsilanes serve as acyl donors in the Pd-catalyzed cross-couplings with allyl trifluoroacetates,243 aryl halides,244 and alkenyl halides.2 Intramolecular acylation of alkynes with acylsilanes proceeds under catalysis by [RhCl(CO)2]2.246... 

When carboxylic acids are treated with trifluoroacetic anhydride, mixed anhydrides (acyl trifluoroacetates) are formed. These compounds are useful acylating agents. What is the product of the reaction of an alcohol with acyl trifluoroacetate ... 

In mixed trifluoroacetic anhydrides, the strong electron-withdrawing tri-fluoroacetyl group polarizes the bonds to the anhydride oxygen in such a way that it tends to split to acylium cation and trifluoroacetate anion [/0/. Generally, the products of the reaction of hydroxy compounds with acyl trifluoroacetates are esters of carboxylic acids and trifluoroacetic acid, because the acyl carbonyl is better fit for a nucleophilic attack than the carbonyl next to the trifluoromethyl group [707]. 

Several acylation transformations of 1,4,7-triazonane were reported. Benzoylation of 1,4,7-triazonane under kine-tical control, that is, through formation of dianion with 2 equiv of -BuLi in THF, led to an 85% yield of mono- and disubstituted compounds in 20 1 ratio <1999JOC7661>. Reaction of triazonane with ethyl trifluoroacetate is a facile method of incorporation of two protecting groups and results in 94% yield of the product when reaction is performed in methanol in the presence of triethylamine <2003TL2481>. 

The Reaction of Acyl Trifluoroacetates with Hydroxy Compounds. 81... 

The role of trifluoroacetic anhydride in these acylations was indicated by the diminished yield of acylation product obtained when the ratio of trifluoroacetic anhydride to hydroxy compound lay below unity, optimum conditions requiring a slight excess of this reagent. A catalytic function was, therefore, excluded, and the view was advanced that trifluoroacetic anhydride serves the purpose of converting the added carboxylic acid into the corresponding acyl trifluoroacetate. Later work on the nature of the equilibria between acyl anhydrides and acids in the presence of trifluoroacetic anhydride showed that the acylating capacity of a mixture of a carboxylic acid and trifluoroacetic anhydride is enhanced by the trifluoroacetic acid liberated when the unsymmetrical anhydride is formed. Further, cryo-scopic studies on solutions in acetic acid of the pure, unsymmetrical anhydride, acetyl trifluoroacetate, have shown that, contrary to an earlier conclusion that acetic anhydride is not formed to any appreciable extent, acetyl trifluoroacetate is, in fact, almost completely converted into acetic anhydride in excess acetic acid. In carrying out an acylation with trifluoroacetic anhydride and a carboxylic acid, it is, therefore, important to avoid an excess of the acid, so that the maximum concentration of the unsymmetrical anhydride is present in the equilibrium system. Extensive studies made on the action of acyl trifluoroacetates on hydroxy compounds under different conditions, with the simultaneous formation of the acyl and trifluoroacetyl derivatives, will be discussed later. 

The rate of acetylation of 0-(hydrox3Tnethyl)cellulose (and other hydroxy compounds) by mixtures of carboxylic acids and their anhydrides has been found to increase greatly in the presence of trifluoroacetic acid. The acceleration is very much less with mono- and tri-chloroacetic acids, presumably because they form unsymmetrical anhydrides which are less effective acylating agents than acyl trifluoroacetates. The exceptional acylating power of the latter anhydrides is shown by their use in the synthesis of alkyl aryl ketones from polyalkylbenzenes, phenyl ethers, furan, and thiophene under mild conditions. The principle has been extended to include acids... 

Oxymercuration of simple alkyl- and acyl-substituted cyclopropenes generally results in ring opening.Addition of mercury(II) acetate to 3-methyl-3-phenylcyclopropene, however, gave a low yield of a cyclopropane containing organomercury compound (15-20%), which was converted into an isomeric mixture of 1 -methoxy-2-methyl-2-phenylcyclopropanes by reduction with lithium aluminum hydride. Reaction of 5 with mercury trifluoroacetate in methanol and then sodium hydroxide led predominantly to one cylopropane. ... 

Studies of Trifluoroacetic Acid. Part XIV, Reaction of Acyl Trifluoroacetates with l 6-Di-0-benzoyl-2 4-3 5-di-0-methylene-D-glucitol, E. J. Bourne, J. Burdon, and J. C. Tatlow,/. Chem. Soc., 1274-1279 (1958). 

The formation of the A-oxide was avoided when trifluoroperacetic acid was reacted with the trifluoroacetate of acetyltropenol (67a, b). Recently it has been shown that hydrogen peroxide in formic acid gave a still better yield of epoxides without detectable A-oxides (67b). Acetylscopine (LXV) has been isolated as the picrate, (m.p. 212°) (67a), identical with the sample obtained from scopine (XLa) (75) hydrochloride by acetyl chloride (67a). The conversion of acetylscopine into ( ) scopolamine (LXV->XLb) has been realized (67b). Hydrolysis with A NaOH in acetone led to scopine (XLa), the hydrochloride of which was acylated, in turn, with acetyltropoyl chloride in nitrobenzene to acetylscopolamine besides a number of by-products. Separation was achieved using cellulose powder chromatography in butanol-A HCl. Acid hydrolysis of this ester with 2A HCl led to ( ) scopolamine hydrochloride (XLb) (67b) identical with the natural... 

Galli, C. 1979. Acylation of arenes and heteroarenes with in situ generated acyl trifluoroacetates. Synthesis 303-304. 

Methyl- and 2,3-dimethylquinoxalines have been acylated with benzoate, trifluoroacetate, oxalate, and phthalate esters using sodium hydride as the condensing agent. Both mono- and diacyl derivatives are obtained from 2,3-dimethylquinoxaline with excess of methyl benzoate and diethyl oxalate the products 55 and 56 are obtained, respectively. Compound 57 is produced by condensation of the dimethyl compound with diethyl phthalate. ... 

The introduction of the tiifluoroacetyl moiety into aromatics and heteroaromatics has been generally realized by Friedel-Crafts acylation and by reaction of organomagnesium or organolithium reagents with ethyl trifluoroacetate, trifluoroacetic acid, or its salts [4—10 and Refs, therein]. 

Allyl ketones are prepared by cross-coupling of allyl esters with acyl metals. For the coupling, allyl trifluoroacetate (306) and the acylstannane 307 were used to provide the ketone 308 [112]. Similarly, acylsilanes such as 310 are used for the coupling with allyl trifluoroacetate 309 to give 311 [113]. For these couplings, use of allyl trifluoroacetate is important. No reaction occurred with allyl acetate. While ligandless palladium trifluoroacetate is most effective, Pd(OAc)2 shows low activity. 

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