Ethyl trifluoroacetate, acylation with

Figure 2.43 Acylation reactions with ethyl trifluoroacetate.

The imidazole by-product is relatively inert and does not cause decomposition of the derivatives [69]. As with the use of ethyl trifluoroacetate as an acylating agent, the unfavourable properties of trifluoroacetic acid produced are eliminated [70]. With the addition of hexamethylenediamine the reaction proceeds rapidly at 60—70°C and the yield is about 70%. If dry ammonia is added to the reaction mixture, the reaction proceeds quantitatively. Ammonia probably neutralizes the residues of trifluoroacetic acid produced by the hydrolysis of the ester and in this way eliminates a competitive acylation reaction. 

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>. 

Selective trifluoroacetylation of primary amines in the presence of secondary amines can be accomplished by reaction with a stoichiometric amount of ethyl trifluoroacetate (bp 60-62 °C) in THF, acetonitrile or dioxane at 0 °C. The product is simply isolated by evaporation of the solvent and liberated ethanol,45-47 Perhaps the most common method entails acylation of the amine with trifluoro-acetic anhydride in the presence of a suitable base such as trie thy lamine or pyridine in dichloromethane [Scheme 8.26],40 New reagents for the N-trifluoro-acetylation of amines include Af-ftrifluoroacetyOsuccinimide,48 a solid and storable reagent, W-(trifluoroacetoxy)succinimide,49 which must be stored in a frozen benzene matrix, and l-(trifluoroacetyl)-l,2,3-benzotriazole.50 The latter reagent is a stable, crystalline reagent (mp 89-91 °C) prepared in quantitative... 

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]. 

Two variants of this basic strategy were developed the first route is shown in Scheme 13. Starting with ethyl 3-furancarboxylate, acylation with monomethylglutarate was effected with trifluoroacetic anhydride (TFAA) and phosphoric acid in acetonitrile to provide keto-furan 37 in 64% yield. Reduction of the ketone to 38 was achieved by treatment with EtaSiH and BFa EtaO (82%... 

On heating with sodium borohydride in glacial acetic acid. 5//-dibenz[/t,/ azepine (5) undergoes sequential acylation and reduction to yield 5-ethyl-5/7-dibcnz[A,/ ]azepine (8, R = Et).192 Similarly, reduction in trifluoroacetic acid produces the trifluoroethyl derivative 8 (R = CF3CH2 61% mp 69-70 C).193... 

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

The 2-(trimethylsilyl)ethyl thioethers are stable towards trifluoroacetic acid under conditions typically used to cleave acetals. The standard acylation and trans-esterification reactions are also fully compatible. Many Lewis acids are tolerated but halogenating agents react. Mild conditions for the cleavage of 2-(trimethyl-sily )ethyl sulfides, which are compatible with many of the standard transformations in carbohydrate chemistry, entails treatment of the thioether in dichloro-... 

A simple procedure for the preparation of trifluoromethylated vinyl- and dienyl-phosphonates with y-alkoxycarbonyl moiety of exclusively or predominantly (Z)-configuration (201) has been described. It involves acylation of ethyl-1,1-bisphosphonate (202) with trifluoroacetic anhydride, addition of selected Reformatsky reagents to the resulting 1-trifluoroacetyl-1,1-ethyl bisphos-phonates (203) and finally spontaneous Horner-Wadsworth-Emmons (HWE) olefination of the adducts (Scheme 55). " ... 

Chen et al. reported a more environmentally friendly version of the Pictet-Spengler reaction <06H1651>. In this report, a series of 2-phenylsulfonyl-l,2,3,4-tetrahydroisoquinoline-1-carboxylic acid ethyl ester derivatives 114 were synthesized in good yields through the cyclization of A-phenylsulfonyl-P-phenethylamines 115 with a-acyl sulfide 116 using phenyliodine(III) bis(trifluoroacetate) (PIFA) in ionic liquid ([bminjPFJ. The use of the ionic liquid allows for a simple purification and [bmin]PF can conveniently be recycled. 

Jacobi s synthesis of ( )-paniculide-A involves an intramolecular Diels-Alder reaction of the alkynic ketone (31). This compound was prepared in >90% yield (Scheme 9) by acylation of a lithium alkynide with the A7-methoxy-A7-methylamide (30). Addition of the anion to other derivatives related to (30) such as an acid chloride, a trifluoroacetic mixed anhydride, an acyl imidazole, S-(2-pyridyl) thiolates and a mixed carbonic anhydride (from ethyl chloroformate) led to either bis-addition or to proton abstraction. Notice should be made of the stability exhibited by the A7-methoxy-A7-methylamide group while the oxa-zole moiety was being introduced. ... 

---