Triethylsilane-Trifluoroacetic Acid1

Et3SiH-CF3CO2H

[617-86-7]  · C6H16Si  · Triethylsilane-Trifluoroacetic Acid  · (MW 116.31)

[599-00-8]  · C2HF3O2  · Triethylsilane-Trifluoroacetic Acid  · (MW 114.03)

(useful reducing agent combination for ionic hydrogenation of many functional groups1)

Physical Data: see Triethylsilane and Trifluoroacetic Acid.

Solubility: Et3SiH: insol H2O; sol hydrocarbons, chlorocarbons, ethers. CF3CO2H: sol H2O, chlorocarbons, ethers.

Form Supplied in: both are colorless liquids; widely available in pure form.

Purification: simple distillation, if needed.

Handling, Storage, and Precautions: triethylsilane is a flammable, nonpyrophoric liquid, physically similar to comparable hydrocarbons. Proper precautions should be taken to vent possible hydrogen buildup when opening vessels in which triethylsilane is stored. As with all organosilicon hydrides, it is capable of releasing hydrogen gas upon storage, particularly in the presence of acids, bases, or fluoride-releasing salts. Trifluoroacetic acid is a corrosive, toxic acid that produces serious chemical burns upon contact with skin.

Introduction.

The reagent combination of Triethylsilane as a hydride donor and Trifluoroacetic Acid (TFA) as a proton donor constitutes a powerful, yet selective, means for the hydrogenation of many functional groups. Many acetals, alcohols, aldehydes, alkenes, cyclopropanes, hemiacetals, ketones, and thiophenes and some alkynes, dihydropyridines, disulfides, enamines, ethers, furans, imidazolones, imines, indoles, O-acyl oximes, sulfides, thiopyrans, p-quinones, and a,b-unsaturated ketones are reduced by this reagent system. Functionalities which are generally unaffected by these reductive conditions include most amide, arene, carboxylate, ester, ether, halide, nitrile, nitro, sulfonate, and phenolic and primary aliphatic hydroxy groups.

The reactions are sometimes run without solvent, but most often a solvent such as MeNO2, CCl4, CHCl3, or, preferably, CH2Cl2 is used. Reactions are performed at room temperature or below and are worked up by careful addition of a base such as solid, anhydrous Potassium Carbonate followed by filtration and distillation to separate the product from the solvent and residual reagents and byproducts.2 Only a slight stoichiometric excess of the silane is normally used, but often several equivalents of acid are used in order to conduct the reductions at reasonable rates.

Specific Functional Group Reductions.

Alcohols capable of producing carbenium ions spanning a range of stabilities of more than 24 pKR+ units are reduced to hydrocarbons when treated with trifluoroacetic acid in the presence of triethylsilane.2 Cyclopropylcarbinols may be reduced to cyclopropane hydrocarbons without ring opening.3 Use of deuteriated silane yields deuterium-labeled hydrocarbons (eq 1).4 Stereospecific reduction of metal-complexed alcohols can be effected without concomitant reduction of isolated terminal C=C bonds (eq 2).5

Sequential treatment of amides, lactams, or ureas with aqueous, basic Formaldehyde followed by triethylsilane and trifluoroacetic acid causes the intermediate methylols to be reduced to the corresponding N-methylated products, generally in very high yields (eq 3).6 Cyclic hemiacetals may be reduced to cyclic ethers with a high degree of stereoselectivity (eq 4).7

Alkenes that yield carbenium ions no more stable than secondary alkyl cations upon protonation do not normally undergo reduction by the action of triethylsilane and trifluoroacetic acid: thus isolated terminal -CH=CH2 groups and simple vicinal 1,2-disubstituted alkenes are normally unaffected, while conjugated or more highly substituted alkene functions are reduced to alkanes.8 Substituted cyclopropanes undergo reductive ring opening,9 but alkynes are nearly inert to these conditions.10 Only the isolated trisubstituted C=C bond is reduced when an unsaturated chroman derivative is treated with a 2-nitropropane solution of triethylsilane and trifluoroacetic acid containing Lithium Perchlorate (eq 5).11

The reagent combination of triethylsilane and trifluoroacetic acid reduces electron-rich or aromatic aldehydes and ketones to a methyl or methylene group, respectively.12 Addition of a catalytic amount of LiClO4 or Boron Trifluoride Etherate to the reaction mixture permits regioselective reduction of the side chain carbonyl group even in polyfunctional enones (eq 6).13 Many aldehydes and ketones react to give symmetrical ethers in the absence of external alcohols14 and unsymmetrical ether products when the reductions are run in the presence of added alcohols (eq 7).15 Reduction of a,b-unsaturated ketones using a ketone:silane:acid ratio; = 1:1:10 gives products with the C=C bond reduced, whereas changing the ratio to 1:3:10 gives products with both the C=C and C=O bonds reduced (eq 8).16

Reduction of O-benzoyl oximes gives O-benzoyl amines (eq 9).17 Tryptophan is reduced and other indoles undergo stereoselective transformations into cis-indolines (eq 10).18

For related discussions, see also the entry on Triethylsilane.


1. (a) Kursanov, D. N.; Parnes, Z. N. RCR 1969, 38, 812. (b) Kursanov, D. N.; Parnes, Z. N.; Loim, N. M. S 1974, 633. (c) Nagai, Y. OPP 1980, 12, 13. (d) Pawlenko, S. MOC 1980, XIII/5, 350. (e) Hajós, A. MOC 1981, IV/1d, 67. (f) Kursanov, D. N.; Parnes, Z. N.; Kalinkin, M. I.; Loim, N. M. Ionic Hydrogenation and Related Reactions; Harwood: Chur, Switzerland, 1985.
2. (a) Carey, F. A.; Tremper, H. S. JACS 1968, 90, 2578. (b) Mayr, H.; Basso, N.; Hagen, G. JACS 1992, 114, 3060.
3. Carey, F. A.; Tremper, H. S. JACS 1969, 91, 2967.
4. (a) Carey, F. A.; Tremper, H. S. JOC 1971, 36, 758. (b) Badejo, I. T.; Karaman, R.; Fry, J. L. JOC 1989, 54, 4591.
5. Uemura, M.; Kobayashi, T.; Hayashi, Y. S 1986, 386.
6. Auerbach, J.; Zamore, M.; Weinreb, S. M. JOC 1976, 41, 725.
7. Kraus, G. A.; Molina, M. T.; Walling, J. A. CC 1986, 1568.
8. (a) Parnes, Z. N.; Beilinson, E. Yu.; Kursanov, D. N. JOU 1970, 6, 2579. (b) Bolestova, G. I.; Parnes, Z. N.; Belikova, N. A.; Kursanov, D. N. BAU 1979, 28, 741.
9. (a) Parnes, Z. N.; Khotimskaya, G. A.; Lukina, M. Y.; Kursanov, D. N. DOK 1968, 178, 88. (b) Parnes, Z. N.; Khotimskaya, G. A.; Kudryavtsev, R. V.; Lukina, M. Y.; Kursanov, D. N. DOK 1969, 184, 66. (c) Parnes, Z. N.; Khotimskaya, G. A.; Kudryavtsev, R. V.; Kursanov, D. N. BAU 1972, 21, 854. (d) Khotimskaya, G. A.; Kudryavtsev, R. V.; Mil'vitskaya, E. M.; Platé, A. F.; Parnes, Z. N. BAU 1972, 21, 1930.
10. Zdanovich, V. I.; Kudryavtsev, R. V.; Kursanov, D. N. BAU 1970, 19, 427.
11. Julia, M.; Roy, P. T 1986, 42, 4991.
12. (a) Kursanov, D. N.; Parnes, Z. N.; Bassova, G. I.; Loim, N. M.; Zdanovich, V. I. T 1967, 23, 2235. (b) West, C. T.; Donnelly, S. J.; Kooistra, D. A.; Doyle, M. P. JOC 1973, 38, 2675.
13. Lakhvich, F. A.; Lis, L. G.; Rubinov, D. B.; Rubinova, I. L.; Akhrem, A. A. JOU 1989, 25, 1493.
14. Doyle, M. P.; DeBruyn, D. J.; Donnelly, S. J.; Kooistra, D. A.; Odubela, A. A.; West, C. T.; Zonnebelt, S. M. JOC 1974, 39, 2740.
15. Doyle, M. P.; DeBruyn, D. J.; Kooistra, D. A. JACS 1972, 94, 3659.
16. (a) Parnes, Z. N.; Loim, N. M.; Baranova, V. A.; Kursanov, D. N. JOU 1971, 7, 2145. (b) Kursanov, D. N.; Loim, N. M.; Baranova, V. A.; Moiseeva, L. V.; Zalukaev, L. P.; Parnes, Z. N. S 1973, 420.
17. Sternbach, D. D.; Jamison, W. C. L. TL 1981, 22, 3331.
18. (a) Pearson, D. A.; Blanchette, M.; Baker, M. L.; Guindon, C. A. TL 1989, 30, 2739. (b) Lanzilotti, A. E.; Littell, R.; Fanshawe, W. J.; McKenzie, T. C.; Lovell, F. M. JOC 1979, 44, 4809.

James L. Fry

The University of Toledo, OH, USA



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