Boron Tris(trifluoroacetate)1


[350-70-9]  · C6BF9O6  · Boron Tris(trifluoroacetate)  · (MW 349.86)

(mild Lewis acid)

Alternate Name: tris(trifluoroacetoxy)borane.

Physical Data: mp 88 °C (dec).

Solubility: decomposes in water exothermically; sol organic solvents.

Preparative Methods: obtained in quantitative yield by the interaction of BCl3 or BBr3 with trifluoroacetic acid.2

Handling, Storage, and Precautions: extremely corrosive to the eyes and skin. If swallowed causes severe internal irritation and damage. Toxic irritating vapor. All work must be carried out in an efficient fume hood.

Deprotection of the N-Terminus of Amino Acids and Peptides.

The major use of tris(trifluoroacetoxy)borane has been to remove protecting groups used during the synthesis of peptides and a-amino acids.3 Although a number of boron-derived reagents, such as Boron Tribromide and Boron Triiodide, are good reagents for the removal of the Z-group (benzyloxycarbonyl) from N-terminal residues in dichloromethane, the partial removal of ester groups has been reported. A further disadvantage is that dichloromethane is not a good solvent for long peptides. On the other hand, the hydroxy groups of serine or threonine and the thiol residue of cysteine are reported not to be attacked by the boron halides. The original communication indicated that a number of important functional groups were unaffected by tris(trifluoroacetoxy)borane.3 The groups included methyl and ethyl esters, methyl ethers, and the amide bond. Benzyl esters were reported, however, to be deprotected. An example is shown in eq 1, in which it was pointed out that optical purity was maintained, but the presence of acid-sensitive groups precludes the use of this method.4

Since the first report, tris(trifluoroacetoxy)borane has been used in a number of peptide syntheses, for example the synthesis of the peptide fragment of the human myelin basic protein.5 The method has been particularly useful in the final removal of protecting groups in those syntheses using the Merrifield technique.6 The deprotection of side chains in peptides required in an investigation of human dihydrofolate reductase used the method successfully.7 Protection with the Z-group and eventual deprotection has been used in structure elucidation, for example in the case of the peptide antibiotics herbicolin A and B.8 In general, there have been few problems reported concerning the use of tris(trifluoroacetoxy)borane. However, although the deprotection shown in eq 2 was achieved very efficiently, the analog in which the unnatural tryptophan was present gave rise to a complex mixture.9

A synthesis of new inhibitors of enkephalin metabolism with improved protection from in vivo enzymic degradation has involved the modification of the C-terminal amino acid by the incorporation of a b-amino acid residue.10 For the N-methyl derivative shown in eq 3, the t-butyl ester was removed using tris(trifluoroacetoxy)borane with simultaneous deprotection of the hydroxyamino group.

In the total synthesis of the antitumor antibiotic acivicin, an a-amino acid, the protective group removal was effected in 56% yield by using Boron Trichloride.11a However, when tris(trifluoroacetoxy)borane was used to remove the Z-group and to cleave the oxazolidinone ring, the yield in the final step was improved to 89% (eq 4).11b

Friedel-Crafts Reactions.

The other use of tris(trifluoroacetoxy)borane has been in Friedel-Crafts reactions.12 In principle the reagent can function as an acylating agent, but only in the case of a reaction using mesitylene (eq 5) did the reaction stop at that stage and afford 2,4,6-trimethyltrifluoroacetophenone (1). It is presumed that this effect is related to a steric problem. With benzene a low yield of 1,1,1-trifluoro-2,2,2-triphenylethane was obtained, but with a more nucleophilic aromatic compound such as anisole, a 90% yield of 1,1,1-trifluoro-2,2,2-tris(p-methoxyphenyl)ethane (2) was obtained (eq 6). With even more nucleophilic substrates, such as 1,3-dimethoxybenzene and phenol, the 1,1-diaryl-2,2,2-trifluoroethanol derivative was obtained. In the example shown, the product (3) was isolated in 82% yield (eq 6).

Related Reagents.

Boron Trifluoride-Acetic Anhydride.

1. (a) Bhatt, M. V.; Kulkarni, S. U. S 1983, 249. (b) Meerwein, H. MOC 1965, 6/3, 143.
2. Gerrard, W.; Lappert, M. F.; Shafferman, R. JCS 1958, 3648.
3. Pless, J.; Bauer, W. AG(E) 1973, 12, 147.
4. Garcia-López, M. T.; González-Muñiz, R.; Molinero, M. T.; Naranjo, J. R.; Del Rio, J. JMC 1987, 30, 1658.
5. Pasaribu, S. J. AJC 1980, 33, 2427.
6. (a) Kagan, H. M.; Williams, M. A.; Williamson, P. R.; Anderson, J. M. JBC 1984, 259, 11 203. (b) Fry, D. C.; Kuby, S. A.; Mildvan, A. S. B 1985, 24, 4680.
7. Tan, X.; Ratnam, M.; Huang, S.; Smith, P. L.; Freisheim, J. H. JBC 1990, 265, 8022.
8. Aydin, M.; Lucht, N.; König, W. A.; Lupp, R.; Jung, G.; Winkelmann, G. LA 1985, 2285.
9. Garcia-López, M. T.; González-Muñiz, R.; Molinero, M. T.; Del Rio, J. JMC 1988, 31, 295.
10. Xie, J.; Soleilhac, J. M.; Schmidt, C.; Peyroux, J.; Roques, B. P.; Fournié-Zaluski, M. C. JMC 1989, 32, 1497.
11. (a) Mzengeza, S.; Yang, C. M.; Whitney, R. A. JACS 1987, 109, 276. (b) Mzengeza, S.; Whitney, R. A., JOC 1988, 53, 4074.
12. Briody, J. M.; Marshall, G. L. S 1982, 939.

Harry Heaney

Loughborough University of Technology, UK

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