[1873-77-4]  · C9H28Si4  · Tris(trimethylsilyl)silane  · (MW 248.73)

(mediator of radical reactions;1,2 nontoxic substitute for tri-n-butylstannane in radical reactions; slower hydrogen donor than tri-n-butylstannane3)

Physical Data: bp 82-84 °C/12 mmHg; d 0.806 g cm-3; n20D 1.489.

Solubility: sol pentane, ether, toluene, THF; modestly sol acetone, acetonitrile; insol H2O; decomposes rapidly in methanol and other alcohols.

Form Supplied in: colorless liquid; commercially available.

Preparative Methods: easy to synthesize.4

Handling, Storage, and Precautions: is slightly sensitive to oxygen and should be stored under nitrogen.5 It showed no toxicity in several biological test systems.6

Functional Group Reductions.

Tris(trimethylsilyl)silane is an effective radical reducing agent for organic halides, selenides, xanthates, isocyanides,2 and acid chlorides (Table 1).7 The reactions are carried out at 75-90 °C in toluene in the presence of a radical initiator, i.e. Azobisisobutyronitrile. Chromatographic workup affords the products. The silicon-containing byproducts are easily separated. The silane can also be used catalytically when Sodium Borohydride is employed as the coreductand.8 If a halide (bromide or iodide) is treated under photochemical initiation conditions with an excess of sodium borohydride and a small amount of tris(trimethylsilyl)silane or its corresponding halide, the silane is continously regenerated from the silyl halide.

Iodides and bromides are reduced by tris(trimethylsilyl)silane to the corresponding hydrocarbons in high yield after a short reaction time (0.5 h). From tertiary to secondary and primary chlorides the reduction becomes increasingly difficult. A longer reaction time and periodic addition of initiator is required. Photochemical initiation can be used and is quite efficient.9 Tris(trimethylsilyl)silane is superior to Tri-n-butylstannane in replacing an isocyanide group by hydrogen. The reaction with tin hydride requires high temperatures (boiling xylene for primary isocyanides) and periodic addition of initiator. Using the silane, primary, secondary, and tertiary isocyanides are reduced at 80 °C in high yields. The reduction of selenides by tris(trimethylsilyl)silane proceeds with high yields; however, the corresponding reaction of sulfides is inefficient.

Acyl chlorides are converted by tris(trimethylsilyl)silane to the corresponding hydrocarbons. Tertiary and secondary acid chlorides react at 80 °C, while the reduction of primary derivatives requires higher temperatures.7 The radical deoxygenation of hydroxyl groups is carried out by conversion of the alcohol to a thionocarbonate, which can be reduced by tris(trimethylsilyl)silane (eq 1). This very mild method is especially useful in natural product synthesis. It has been utilized for the deoxygenation of lanosterol (eq 2)6 and the dideoxygenation of 1,6-anhydro-D-glucose (eq 3).10

Radical deoxygenation of the cis-unsaturated fatty acid derivative with tris(trimethylsilyl)silane gives methyl triacont-21-trans-enoate together with the saturated compound (eq 4). If the reaction is carried out with tri-n-butyltin hydride, the configuration remains unchanged.11

Hydrosilylation of Double Bonds.

Tris(trimethylsilyl)silane is capable of radical hydrosilylation of dialkyl ketones,12 alkenes,12,13 and alkynes.13 Hydrosilylation of alkenes yields the anti-Markovnikov products with high regio- and good diastereoselectivity (eq 5). By using a chiral alkene, complete stereocontrol can be achieved (eq 6).14 The silyl group can be converted to a hydroxyl group by Tamao oxidation.13

Monosubstituted alkynes give alkenes in high yield and stereoselectivity. The formation of (E)- or (Z)-alkenes depends on the steric demand of the substituents (eq 7). 1,2-Disubstituted phenylalkynes are attacked exclusively b to the phenylated alkyne carbon atom.13 The silyl moiety can be replaced by a bromine atom with overall retention of configuration (eq 8).13

The hydrosilylation of ketones is in general slower than the corresponding reaction of alkenes and alkynes. In the case of sterically hindered ketones, a catalytic amount of a thiol is necessary to carry out the reaction.15 The resulting silyl ethers can be easily desilylated by standard procedures. With 4-t-butylcyclohexanone the trans isomer is formed as the main product (eq 9). The hydrosilylation of a ketone bearing a chiral center in the adjacent position yields mainly the Felkin-Anh product (eq 10).15

Intramolecular Reactions.

Tris(trimethylsilyl)silane is an effective mediator of radical cyclizations.16 In addition to halides and selenides, secondary isocyanides can be used as precursors for intramolecular C-C bond formation,17 which is impossible using the tin hydride (eq 11). Selective cleavage of the carbon-sulfur bond of a 1,3-dithiolane, 1,3-dithiane,18 1,3-oxathiolane, or 1,3-thiazolidine19 derivative is an efficient process to generate carbon-centered radicals, which can undergo cyclization (eq 12).

2-Benzylseleno-1-(2-iodophenyl)ethanol reacts smoothly with tris(trimethylsilyl)silane to give benzo[b]selenophene (eq 13).20 A similar homolytic substitution reaction at the silicon atom yields a sila bicycle.21

The silane is superior to the tin reagent in the radical rearrangement of glycosyl halides to 2-deoxy sugars (eq 14).16 Aromatization of the A-ring of 9,10-secosteroids can be achieved by a mild, radical-induced fragmentation reaction of 3-oxo-1,4-diene steroids (eq 15).22

Intermolecular Reactions.

Radical carbon-carbon bond formation can be carried out with tris(trimethylsilyl)silane.16 Again, it is possible to use isocyanides as precursors (eqs 16 and 17).17

Nonradical Reactions.

Tris(trimethylsilyl)silane reacts with carbenium ions to form a silicenium ion.23 In this case, tris(trimethylsilyl)silane is only slightly more reactive than trimethylsilane. The reaction of the silane with methyl diazoacetate in the presence of copper catalyst gives the a-silyl ester (eq 18).24

1. Chatgilialoglu, C. ACR 1992, 25, 188.
2. Ballestri, M.; Chatgilialoglu, C.; Clark, K. B.; Griller, D.; Giese, B.; Kopping, B. JOC 1991, 56, 678.
3. Chatgilialoglu, C.; Dickhaut, J.; Giese, B. JOC 1991, 56, 6399.
4. Dickhaut, J.; Giese, B. OS 1991, 70, 164.
5. Chatgilialoglu, C.; Guarini, A.; Guerrini, A.; Seconi, G. JOC 1992, 57, 2207.
6. Schummer, D.; Höfle, G. SL 1990, 705.
7. Ballestri, M.; Chatgilialoglu, C.; Cardi, N.; Sommazzi, A. TL 1992, 33, 1787.
8. Lesage, M.; Chatgilialoglu, C.; Griller, D. TL 1989, 30, 2733.
9. Chatgilialoglu, C.; Griller, D.; Lesage, M. JOC 1988, 53, 3641.
10. Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. C. TL 1992, 33, 6629.
11. Johnson, D. W.; Poulos, A. TL 1992, 33, 2045.
12. Kulicke, K. J.; Giese, B. SL 1990, 91.
13. Kopping, B.; Chatgilialoglu, C.; Zehnder, M.; Giese, B. JOC 1992, 57, 3994.
14. Smadja, W.; Zahouily, M.; Malacria, M. TL 1992, 33, 5511.
15. Giese, B.; Damm, W.; Dickhaut, J.; Wetterich, F.; Sun, S.; Curran, D. P. TL 1991, 32, 6097.
16. Giese, B.; Kopping, B.; Chatgilialoglu, C. TL 1989, 30, 681.
17. Chatgilialoglu, C.; Giese, B.; Kopping, B. TL 1990, 31, 6013.
18. Arya, P.; Samson, C.; Lesage, M.; Griller, D. JOC 1990, 55, 6248.
19. Arya, P.; Lesage, M.; Wayner, D. D. M. TL 1991, 32, 2853. Arya, P.; Wayner, D. D. M. TL 1991, 32, 6265.
20. Schiesser, C. H.; Sutej, K. TL 1992, 33, 5137.
21. Kulicke, K. J.; Chatgilialoglu, C.; Kopping, B.; Giese, B. HCA 1992, 75, 935.
22. Künzer, H.; Sauer, G.; Wiechert, R. TL 1991, 32, 7247.
23. Mayr, H.; Basso, N.; Hagen, G. JACS 1992, 114, 3060.
24. Watanabe, H.; Nakano, T.; Araki, K.-I.; Matsumoto, H.; Nagai, Y. JOM 1974, 69, 389.

Bernd Giese & Joachim Dickhaut

University of Basel, Switzerland

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