3-Trimethylsilyl-3-buten-2-one

[43209-86-5]  · C7H14OSi  · 3-Trimethylsilyl-3-buten-2-one  · (MW 142.30)

(methyl vinyl ketone homolog1 useful as a Michael acceptor in annulation reactions,2,3 g,d-unsaturated ketone formation,4 and Peterson condensations;5 precursor to a stabilized Diels-Alder diene6)

Physical Data: bp 72 °C/50 mmHg.

Analysis of Reagent Purity: 1H NMR (CCl4): d 6.53 (d, J = 2 Hz, 1H, CH), 6.18 (d, J = 2 Hz, 1H, CH), 2.23 (s, 3H, CH3), 0.14 [s, 9H, Si(CH3)3]. Analysis by gas chromatography on a 1.85m 3% silicon gum rubber (SE-30) column at 25 °C gives a single peak.

Preparative Methods: prepared by the reaction of (1-Bromovinyl)trimethylsilane with Acetaldehyde.1 An alternative synthesis from Acrolein has been published.7

Handling, Storage, and Precautions: shows no tendency to deteriorate when stored under an argon atmosphere at -20 °C.

Annulation.

3-Trimethylsilyl-3-buten-2-one has been employed as a Methyl Vinyl Ketone homolog in an improved method for the annulation of ketones.2 Based on work by Stork and Ganem,3 who employed 3-Triethylsilyl-3-buten-2-one as a Michael acceptor in the Robinson annulation reaction, Suzuki and co-workers8 prepared a functionalized bicyclic ketone via a silyl enol ether as shown in eq 1. In general, the annulation of 2-alkylcycloketones with methyl vinyl ketone and its homologs produces rather poor yields of the desired cyclized products.

The conjugate addition of enolate anions to activated 3-trimethylsilyl-3-buten-2-one helped solve another long-standing problem in organic synthesis by permitting the annulation reaction to be carried out in aprotic solvents under conditions where enolate equilibration is avoided. The annulation of thermodynamically unstable lithium enolates with MVK, where equilibration to the more stable enolate occurs prior to Michael addition, often yields a mixture of structural isomers.9 For example, Boeckman successfully employed 3-trimethylsilyl-3-buten-2-one in a Robinson annulation sequence (eq 2). Thus treatment of cyclohexenone with Lithium Dimethylcuprate in diethyl ether and then with 3-trimethylsilyl-3-buten-2-one gives the desired Michael adduct, which is converted into the functionalized octalone in 52% overall yield.10

Boeckman originally postulated that the enolate copper bond played a part in the success of this sequence. In 1974, however, Boeckman11 and Stork and Singh12 reported simultaneously that lithium enolates can be used under aprotic conditions for regiospecific annulation with 3-trimethylsilyl-3-buten-2-one (eq 3).

The most general annulation procedure is to first generate an enolate by lithium-ammonia reduction of an enone in the presence of t-butanol; the enolate is then trapped as the trimethylsilyl enol ether, which can be examined spectroscopically to establish homogeneity. The enolate is then regenerated with Methyllithium in dry glyme or diethyl ether at -78 °C prior to the addition of the a-silylated vinyl ketone. In this case, only traces of the linear tricyclic ketone are formed. The trimethylsilyl group helps stabilize the intermediate carbanion formed by conjugate addition, relative to that of the starting ketone, thus facilitating the forward reaction and at the same time discouraging equilibration of the enolate of the starting ketone.

Michael Condensation.

In 1988, Hagiwara and co-workers extended this annulation technology to include the two-fold Michael reaction of kinetic enolates derived from 1-acetylcyclohexenes (eq 4).13 The kinetic enolates of 1-acetylcyclohexenes are generated from the corresponding trimethylsilyl enol ethers by treatment with MeLi in THF prior to the addition of 3-trimethylsilyl-3-buten-2-one. This one-pot annulation produces the desired decalone as a single isomer in 39% yield.

1-Alkenyldialkoxyboranes also react with 3-trimethylsilyl-3-buten-2-one in the presence of Boron Trifluoride Etherate through a facile 1,4-addition to give g,d-unsaturated ketones in good yields with high regio- and stereoselectivity (eq 5). Without BF3 etherate this reaction does not occur and other Lewis acids, such as AlCl3, TiCl4, SnCl4, and ZnCl2, are less effective.4

Michael-Peterson Condensation.

3-Trimethylsilyl-3-buten-2-one also undergoes smooth Michael addition with Grignard reagents (R = Me, n-Pr, i-Pr, t-Bu, Ph), generating magnesium enolates which are then trapped with benzaldehyde to give (E)- and (Z)-enone isomers after Peterson condensation (eq 6).5 For example, treatment of the a-silyl vinyl ketone with methylmagnesium iodide followed by reaction with benzaldehyde yields a 7:1 mixture of (E)- and (Z)-isomers of 3-ethyl-4-phenyl-3-buten-2-one in 45% yield. (E)-Alkenes become the major products under thermodynamic control when the condensation with benzaldehyde is carried out at room temperature in diethyl ether. (Z)-Isomers are favored as kinetically controlled products at -78 °C in THF.

Diene Adduct.

3-Trimethylsilyl-3-buten-2-one undergoes a Shapiro reaction to give the 2,3-bis(trimethylsilyl)buta-1,3-diene in 32% yield (eq 7). This compound undergoes Diels-Alder reactions with a number of dienophiles (e.g. maleic anhydride, benzoquinone) in benzene at 60 °C to give silylated cycloaddition adducts.6


1. Boeckman, R. K., Jr.; Blum, D. M.; Ganem, B.; Halvey, N. OSC 1988, 6, 1033.
2. (a) Shishido, K.; Hiroya, K.; Fukumoto, K.; Kametani, T. JCS(P1) 1986, 837. (b) Bonnert, R. V.; Jenkins, P. R. CC 1987, 6. (c) Murai, A.; Tanimoto, N.; Sakamoto, N.; Masamune, T. JACS 1988, 110, 1985. (d) Rigby, J. H.; Kierkus, P. C.; Head, D. TL 1989, 30, 5073. (e) Paquette, L. A.; Sauer, D. R.; Cleary, D. G.; Kinsella, M. A.; Blackwell, C. M.; Anderson, L. G. JACS 1992, 114, 7375.
3. Stork, G.; Ganem, B. JACS 1973, 95, 6152.
4. Hara, S.; Hyuga, S.; Aoyama, M.; Sato, M.; Suzuki, A. TL 1990, 31, 247.
5. Tanaka, J.; Kobayashi, H.; Kanemasa, S.; Tsuge, O. BCJ 1989, 62, 1193.
6. Garratt, P. J.; Tsotinis, A. TL 1986, 27, 2761.
7. Okumoto, H.; Tsuji, J. SC 1982, 12, 1015.
8. Suzuki, T.; Sato, E.; Unno, K.; Kametani, T. CC 1988, 724.
9. Marshall, J. A.; Fanta, W. I. JOC 1964, 29, 2501, and references cited therein.
10. (a) Boeckman, R. K., Jr. JACS 1973, 95, 6867. (b) Boeckman, R. K., Jr.; Blum, D. M.; Ganem, B. OSC 1988, 6, 666. (c) See also: Takahashi, T.; Naito, Y.; Tsuji, J. JACS 1981, 103, 5261.
11. Boeckman, R. K., Jr. JACS 1974, 96, 6179.
12. Stork, G.; Singh, J. JACS 1974, 96, 6181.
13. Hagiwara, H.; Akama, T.; Okano, A.; Uda, H. CL 1988, 1793.

Bradley B. Brown

University of California, Berkeley, CA, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.