Sodium Tris(trifluoroacetoxy)borohydride1


[76791-24-7]  · C6HBF9NaO6  · Sodium Tris(trifluoroacetoxy)borohydride  · (MW 373.87)

(a reducing agent for many different functional groups and heterocycles;1 can serve as a source of trifluoroacetaldehyde or its equivalent;2 is similar to other ionic hydrogenation methods in the facile reduction of benzylic systems3)

Physical Data: mp 64-66 °C.4

Solubility: is rapidly destroyed by H2O and protic solvents; H2 is liberated. Common cosolvents for the reactions of this reagent are CH2Cl2, THF, toluene, and Et2O.

Form Supplied in: not commercially available.

Preparative Methods: normally prepared in situ by the reaction of excess Trifluoroacetic Acid with Sodium Borohydride.1,4

Analysis of Reagent Purity: has been characterized by elemental analysis and IR.4

Handling, Storage, and Precautions: the preparation of and all reactions involving this reagent should be conducted under an inert atmosphere because H2 may be liberated; this is particularly true when NaBH4 powder is used; NaBH4 pellets are particularly convenient and safe to use for the preparation of NaBH(OCOCF3)3.

Functional Group Reductions.

The combination of strong acid and hydride donor provides a unique and powerful reagent for the deoxygenation of benzylic alcohols and aryl ketones, the reduction of imines, enamines, oximes, and related double bonds, and the reduction of heterocycles (indoles, pyrroles, and some p-deficient heterocyclic systems). The deoxygenation of benzylic alcohols via carbocations is limited to diarylcarbinols,3,5 triarylcarbinols,3 and a few activated monobenzylic systems (eqs 1-3),6 but a wide range of functional groups is tolerated by the reaction conditions. Generally, excess CF3CO2H is employed and, in these cases, the reducing species is assumed to be NaBH(OCOCF3)3,2,3 although in some cases Sodium Trifluoroacetoxyborohydride may be involved.5,6 Recent examples abound.7

Diaryl ketones and a few aryl ketones are deoxygenated by NaBH4 in CF3CO2H and a wide range of functional groups may be present in the substrate (CO2Me, CN, NO2, halogen, CO2H, CONHPh, NMe2, OMe).8 Some examples are shown (eqs 4-8).9

1,1-Diphenylethylene is reduced to 1,1-diphenylethane in 93% yield,3 presumably via the carbocation.

Whereas indoles containing a second, basic nitrogen are normally not reduced by Sodium Triacetoxyborohydride, they are reduced by the combination NaBH4 or Sodium Cyanoborohydride and CF3CO2H (eqs 9-11).10-12

The combination of NaBH3CN-CF3CO2H, which smoothly reduces even deactivated indole rings (eqs 10 and 11),11 also reduces some pyrroles (eqs 12 and 13).13

Benzylic acetals are reductively cleaved with NaBH3CN-CF3CO2H14,15 (eq 14),15 as are arene 1,4-oxides16 and ozonides.17

Iminium ions, whether generated from imines, enamines, or carbinol amines, are readily reduced by NaBH4-CF3CO2H (eqs 15-18).18-21

Oximes are also reduced to amines (eqs 19 and 20).22-24

The N-trifluoroethylation of amines occurs with NaBH4-CF3CO2H (eq 21),25 presumably via CF3CHO or its equivalent,1,2 and has been observed by several groups.1 CF3CO2H can serve as a useful medium for the NaBH4-Paraformaldehyde methylation of amines (eq 22).26

In a reaction (Baeyer condensation) reminiscent of the classic DDT synthesis, the combination NaBH4-CF3CO2H leads to the formation of bis-arenes (eqs 23 and 24).2,25

A few p-deficient heterocycles, such as quinoxaline (eq 25)27 and pyrido[2,3-b]pyrazine (eq 26),27 are reduced by NaBH4-CF3CO2H.

1. (a) Gribble, G. W.; Nutaitis, C. F. OPP 1985, 17, 317. (b) Nutaitis, C. F. J. Chem. Educ. 1989, 66, 673.
2. Nutaitis, C. F.; Gribble, G. W. S 1985, 756.
3. Gribble, G. W.; Leese, R. M.; Evans, B. E. S 1977, 172.
4. Oklobdzija, M.; Fajdiga, T.; Kovac, T.; Zonno, F.; Sega, A.; Sunjic, V. Acta Pharm. Jugosl. 1980, 30, 121.
5. Nutaitis, C. F.; Patragnoni, R.; Goodkin, G.; Neighbour, B.; Obaza-Nutaitis, J. OPP 1991, 23, 403.
6. Nutaitis, C. F.; Bernardo, J. E. SC 1990, 20, 487.
7. (a) Lai, Y.-H.; Peck, T.-G. AJC 1992, 45, 2067. (b) Bauder, C.; Ocampo, R.; Callot, H. J. SL 1990, 335. (c) Osuka, A.; Zhang, R. P.; Maruyama, K.; Yamazaki, I.; Nishimura, Y. BCJ 1992, 65, 2807. (d) Kotha, S.; Kuki, A. CC 1992, 404. (e) Nicholas, K. M.; Siegel, J. JACS 1985, 107, 4999.
8. Gribble, G. W.; Kelly, W. J.; Emery, S. E. S 1978, 763.
9. (a) Lee, C.-M.; Parks, J. A.; Bunnell, P. R.; Plattner, J. J.; Field, M. J.; Giebisch, G. H. JMC 1985, 28, 589. (b) Daich, A.; Decroix, B. JHC 1992, 29, 1789. (c) Kurokawa, M.; Uno, H.; Itogawa, A.; Sato, F.; Naruto, S.; Matsumoto, J. JHC 1991, 28, 1891.
10. (a) Gribble, G. W.; Johnson, J. L.; Saulnier, M. G. H 1981, 16, 2109. (b) Gribble, G. W.; Lord, P. D.; Skotnicki, J.; Dietz, S. E.; Eaton, J. T.; Johnson, J. L. JACS 1974, 96, 7812.
11. Ketcha, D. M.; Lieurance, B. A. TL 1989, 30, 6833.
12. Takayama, H.; Seki, N.; Kitajima, M.; Aimi, N.; Seki, H.; Sakai, S. H 1992, 33, 121.
13. Ketcha, D. M.; Carpenter, K. P.; Zhou, Q. JOC 1991, 56, 1318.
14. Nutaitis, C. F.; Gribble, G. W. OPP 1985, 17, 11.
15. Johansson, R.; Samuelsson, B. CC 1984, 201.
16. Gribble, G. W.; Kelly, W. J.; Sibi, M. P. S 1982, 143.
17. Fujisaka, T.; Nojima, M.; Kusabayashi, S. JOC 1985, 50, 275.
18. Henrie, R. N., II; Lazarus, R. A.; Benkovic, S. J. JMC 1983, 26, 559.
19. Comins, D. L.; Weglarz, M. A. JOC 1991, 56, 2506.
20. Basha, A.; Orlando, J.; Weinreb, S. M. SC 1977, 7, 549.
21. Jefford, C. W.; Wang, J. B. TL 1993, 34, 2911.
22. Umino, N.; Iwakuma, T.; Ikezaki, M.; Itoh, N. CPB 1978, 26, 2897.
23. Branchaud, B. P. JOC 1983, 48, 3531.
24. Wu, P.-L.; Chu, M.; Fowler, F. W. JOC 1988, 53, 963.
25. Gribble, G. W.; Nutaitis, C. F.; Leese, R. M. H 1984, 22, 379.
26. Gribble, G. W.; Nutaitis, C. F. S 1987, 709.
27. Bugle, R. C.; Osteryoung, R. A. JOC 1979, 44, 1719.

Gordon W. Gribble

Dartmouth College, Hanover, NH, USA

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