Trifluoroacetyl protecting group

Peptide synthesis. The reagent is used to prepare N-trifluoroacetyl derivatives of amino acids and peptides. The substrate is warmed with 1.2-2 equivalents of the reagent in molten phenol at 120-150° for 2-20 min. Excess reagent and phenol are removed under vacuum or by solution in petroleum ether or carbon tetrachloride, from which the amino acid derivative crystallizes. The main advantage of the N-trifluoroacetyl protective group is that it can be removed under very mild conditions. 1,. Benoiton, H. N. Rydon, andJ. E. Willett, Chem. Ind., 1060(1960)... 

As shown in Scheme 36, a Heck polyannulation reaction was realized between dibromo(indolyl)maleimide 209 and diacetylenyl trifluoroacetanilide 210 to assemble indolo[2.3-a]carbazole 211, the Af-prolecied aglycone of rebeccamycin (25). Four bonds were formed in one step from a single monocyclic 1,3-diacetylene precursor [101] and the trifluoroacetyl protecting groups were readily cleaved during the workup. 

Trifluoroacetyl protecting group, 135, 254 Triglycolic acid, JV.iV -biscarbonylimidazole derivative, 112... 

The final step in the synthesis of the target molecule, sulfanilamide, is the conversion of the sulfonyl chloride intermediate to a sulfonamide and the removal of the 2,2,2-trifluoroacetyl protecting group. These transformations are accomplished in one step because both reactions take place upon heating the protected sulfonyl chloride with aqueous ammonia. The reaction sequence is shown here ... 

Because of the strong electron-withdrawing effect of the trifluoromethyl group, trifluoroacetamides are subject to hydrolysis under mild conditions. This has permitted trifluoroacetyl groups to be used as amino-protecting groups in some situations. 

For modified nucleosides bearing trifluoroacetyl-protected amino groups, after step 3 of Protocol 10, add one volume of 33% aqueous ammonia solution to the reaction and stir at room temperature overnight. Then evaporate the solution to an oil, redissolve in 50 mM TEAB and purify by MPLC according to Protocol 19. 

Trifluoroacetic acid anhydride reacts exclusively with the amino moiety of the amino alcohol 5, The trifluoroacetyl group has long been known as a valuable protecting group. ... 

Complexation of dihydronaphthalene with chromium tricarbonyl facilitates the attack of a nucleophilic amine and stereoselectively directs the protonation "anti" to the metal atom. (+)-(l S,2 R)-, 2-Dihydro-7-methoxy-1,4-dimethyl-1 - 2 -[methyl(trifiuoroacetyl)amino]propyl -naphthalene [(+)-7] was treated with chromium hexacarbonyl to give a mixture of a- and /(-chromium tricarbonyl complexes in a 10 1 ratio ( H NMR). The complexes were separated and the a-isomer cyclized by base treatment and sonication. Dccomplexation gave the ben-zomorphan tricycle 8 in low yield [40%, based on recovered (+)-7]18. The trifluoroacetyl protection of the amino group was necessary to achieve both stereoselective complexation with chromium tricarbonyl and successful cyclization. 

More recently, the 2-(trifluoroacetyl)vinyl group (4,4,4-trifluoro-3-oxobut-l-enyl, 126) was proposed for the N-protection of amino acids.This enamine derivative is readily prepared with 4-ethoxy-l,l,l-trifluorobut-3-en-2-one and NaOH at room temperature in 1-3 hours. Acidic workup leads to the protected amino acids in yields ranging from 70-89% without racemization. Cleavage is achieved with 3 M HCl in dioxane at room temperature in 10 hours. 

The Af -acyl groups used in these protection schemes are the formyl and trifluoroacetyl groups. With the advent of alternative alkali-labile amine protecting groups that are cleaved via (3-elimination under milder basic conditions, e.g. 9-fluorenylmethoxycarbonyl (see Section 2.1.1.1.1.3) and substituted sulfonylethyloxycarbonyl groups (see Section 2.1.1.1.1.4), the... 

In this section, the protections and cleavages of seven protecting groups for amines and anilines aie presented benzyl BOC Cbz Fmoc phthaloyl sulfonamide and trifluoroacetyl. 

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