[5908-40-7]  · C6H14OSi  · Trimethylsilylacetone  · (MW 130.29)

(reacts with Grignard or organolithium reagents to provide, after elimination, 2-substituted 2-propenes;2 in combination with fluoride ion, gives chemistry of the corresponding enolate ion;3 can direct electrophilic substitution to either side of the carbonyl group3b,4)

Physical Data: clear liquid; bp 74 °C/96 mmHg; d 0.8274 g cm-3 (26 °C), n26D 1.4188.

Preparative Methods: the best procedure for the preparation of trimethylsilylacetone is the reaction of Trimethylsilylmethylmagnesium Chloride or bromide with Acetic Anhydride.5 Other useful preparative methods for a-trimethylsilyl ketones involve the reaction of trimethylsilylmethylmagnesium chloride with acid chlorides,6 or with aldehydes followed by oxidation of the resulting b-hydroxysilane to the ketone.2e When the trialkylsilyl group is very large, particularly the triisopropylsilyl group, a rearrangement from the silyl enol ether to the a-silyl ketone is possible.7

Handling, Storage, and Precautions: a-trimethylsilyl ketones thermally rearrange to the more stable silyl enol ethers at temperatures above approximately 100 °C and normally within 1 h at 140 °C or above; they hydrolyze to the parent ketone upon treatment with acid or base and are difficult to purify by chromatography due to desilylation; use in a fume hood.

Preparation of 2-substituted a-Alkenes.

The reaction of trimethylsilylacetone with Grignard and organolithium reagents has been employed in the synthesis of 2-substituted propenes via the formation of a b-hydroxysilane, which is then subjected to a Peterson elimination (eq 1).2 It was also used to prepare b,g-unsaturated esters, nitriles, and amides (eq 2).2b

The reaction of acid chlorides with 2 equiv of a trimethylsilylmethyl organometallic reagent, where the metal can be chloromagnesium, lithium, or, best, dichlorocerium, proved to be an excellent direct synthesis of allylsilanes via the intermediacy of an a-trimethylsilyl ketone (eq 3).2d By reaction of a-trimethylsilyl ketones with Vinylmagnesium Bromide, one can prepare 2-substituted 1,3-butadienes (eq 4).2c,2f

Reaction with Electrophiles.

The electrophilic substitution of a-silyl ketones gives the same products as those derived from the corresponding silyl enol ether. Thus reaction with Bromine or Thionyl Chloride gives the a-bromo (or chloro) ketone, with the halogen replacing the trimethylsilyl group (eq 5).4a,b

The Lewis acid-catalyzed reaction with aldehydes results in aldol condensation to give the b-hydroxy ketone with substitution on the side of the trimethylsilyl group as would be the case with the silyl enol ether. One potential advantage of this reaction is the ability to control the regioselectivity through the synthesis of the a-silyl ketone (eq 6).3b

Electrophilic reaction with acetals is also possible, as shown with the optically active acetal (eq 7), which gives very high diastereoselectivity.8 This has been employed in an approach to aklavinone9 and cis-2-substituted 6-methylpiperidines.4e

Reaction with Fluoride Ion.

The reaction of a-trimethylsilyl ketones with fluoride ion results in attack of the fluoride ion on the trimethylsilyl group and formation of the corresponding enolate ion. This represents an in situ method for regioselective generation of the enolate ion in the presence of the electrophile (eqs 8 and 9). This can be especially advantageous when the more substituted enolate ion is desired.3

Reaction with Strong Bases.

Trimethylsilylmethyl ketones that do not carry another a-substituent can be regioselectively deprotonated on the side bearing the trimethylsilyl group (eq 10). This can lead to a,b-unsaturated ketones when the resulting enolate reacts with aldehydes (eq 11).10

The enolate chemistry of a-substituted a-trimethylsilyl ketones can be directed to either side of the ketone. Thus deprotonation with LDA occurs away from the trimethylsilyl side for steric reasons (eq 12), whereas Lewis acid-catalyzed reactions occur on the trimethylsilyl side of the molecule (eq 13).10

Related Reagents.

t-Butyl Trimethylsilylacetate; N,N-Dimethyl-2-(trimethylsilyl)acetamide; Ethyl 2-(Methyldiphenylsilyl)propanoate; Ethyl Trimethylsilylacetate; Trimethylsilylacetic Acid.

1. For a review of a-silyl ketones and a-silyl carbonyl compounds consult: (a) Brook, A. G. ACR 1974, 7, 77. (b) Larson, G. L. PAC 1990, 62, 2021.
2. (a) Hudrlik, P. F.; Peterson, D. TL 1972, 1785. (b) Ruden, R. A.; Gaffney, B. L. SC 1975, 5, 15. (c) Brown, P. A.; Bonnert, R. V.; Jenkins, P. R.; Selim, M. R. TL 1987, 28, 693. (d) Anderson, M. B.; Fuchs, P. L. SC 1987, 17, 621. (e) Hudrlik, P. F.; Peterson, D. JACS 1975, 97, 1464. (f) Brown, P. A.; Jenkins, P. R.; Fawcett, J.; Russell, D. R. CC 1984, 253.
3. (a) Fiorenza, M.; Mordini, A.; Papaleo, S.; Pastorelli, S.; Ricci, A. TL 1985, 26, 787. (b) Inoue, T.; Sato, T.; Kuwajima, I. JOC 1984, 49, 4671. (c) Paquette, L. A.; Blankenship, C.; Wells, G. J. JACS 1984, 106, 6442.
4. (a) Sato, S.; Matsuda, I.; Izumi, Y. TL 1985, 26, 1527. (b) Benneche, T.; Christiansen, M. L.; Undheim, K. ACS 1986, B40, 700. (c) Kuwajima, I.; Inoue, T.; Sato, T. TL 1978, 4887. (d) Pellon, P.; Hamelin, J. TL 1986, 27, 5611. (e) Ryckman, D. M.; Stevens, R. V. JOC 1987, 52, 4274. (f) McNamara, J. M.; Kishi, Y. JACS 1982, 104, 7371. (g) Trost, B. M.; Schneider, S. JACS 1989, 111, 4430.
5. Hauser, C. R.; Hance, C. R. JACS 1952, 74, 5091.
6. Chan, T. H.; Chang, E.; Vinokur, E. TL 1970, 1137.
7. Corey, E. J.; Rücker, C. TL 1984, 25, 4345.
8. Johnson, W. S.; Edington, C.; Elliot, J. D.; Silverman, I. R. JACS 1984, 106, 7588.
9. Pearlman, B. A.; McNamara, J. M.; Hasan, I.; Hatakeyama, S.; Sekizaki, H.; Kishi, Y. JACS 1981, 103, 4248.
10. Matsuda, I.; Okada, H.; Sato, S.; Izumi, Y. TL 1984, 25, 3879.

Gerald L. Larson

Hüls America, Piscataway, NJ, USA

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