Trimethylsilylacetonitrile

[18293-53-3]  · C5H11NSi  · Trimethylsilylacetonitrile  · (MW 113.26)

(a-carbanion is a useful alternative to LiCH2CN for nucleophilic cyanomethylation; (Z)-selective Peterson alkenation)

Physical Data: bp 84-85 °C/54 mmHg,1 66 °C/35 mmHg,2 65-70 °C/20 mmHg;3 d 0.827 g cm-3.

Solubility: sol most common organic solvents.

Form Supplied in: liquid; commercially available.

Preparative Methods: from Chlorotrimethylsilane, Zinc, and XCH2CN, (X = Cl, 61% yield; X = Br, 81% yield).3

Handling, Storage, and Precautions: is an organic cyanide and should be handled with due care in a fume hood.

Metalation.

Exposure to Lithium Diisopropylamide or n-Butyllithium in ether3 or THF at -78 °C generates lithiotrimethylsilylacetonitrile [70980-14-2], which is stable at -78 to -20 °C.3-5

Peterson Alkenation (Cyanomethylenation).

The anion, typically lithiotrimethylsilylacetonitrile, undergoes Peterson alkenations with aldehydes to furnish a,b-unsaturated nitriles, principally as the (Z) isomer (eq 1),6-9 in contrast to the Horner-Emmons-Wittig condensation, which gives predominantly the (E) isomer.9 Use of the boronate-stabilized anion of trimethylsilylacetonitrile, especially in the presence of HMPA, increases the (Z) selectivity (eq 1) but no effect is observed in the case of benzaldehyde.6,7 Acyclic a-chlorocarbonyl compounds8 exhibit poor (E/Z) stereoselectivity. Other trialkylsilylacetonitriles (e.g. Ph3SiCH2CN, t-BuMe2SiCH2CN)6,7 exhibit similar (E/Z) stereoselectivity, but higher homologs of trimethylsilylacetonitrile (e.g. Me2PhSiCH(Me)CN, Me2PhSiCH(Et)CN) give 1:1 (E/Z) mixtures.10

Michael Addition.

The reaction of a,b-unsaturated aldehydes3,6 and ketones11,12 with trimethylsilylacetonitrile proceeds with 1,2- and 1,4-regioselectivity, respectively. A synthesis of (+)-sesbanimide11,13 highlights the utility of trimethylsilylacetonitrile in a Michael addition to an a,b-unsaturated ester: lithiotrimethylacetonitrile gives exclusively the 1,4-addition product, whereas Lithioacetonitrile gives mainly the 1,2-addition product. Desilylation of the former adduct results in the product of overall 1,4-addition of lithioacetonitrile.

Reactions with Other Electrophiles.

The anion of trimethylsilylacetonitrile reacts with allylic, propargylic, and benzylic bromides,14 with some alkyl bromides and iodides,5,14 with epoxides to afford g-(trimethylsilyloxy)nitriles,3 and with Me3GeCl,15 Me3SiCl,16 and (Me3SiO)217 to afford the expected a-substitution products. Trimethylsilylacetonitrile also reacts with (n-Bu)3SnOMe18 to afford (n-Bu)3SnCH2CN.

Cyanomethylation.

Trimethylsilylacetonitrile is a useful synthetic equivalent for the anion of acetonitrile in condensation reactions with carbonyl compounds19-21 and glycosyl fluorides,22 leading to b-(trimethylsilyloxy)nitriles (eq 2)21 and cyanomethyl glycosides, respectively. However, the addition of trimethylsilylacetonitrile to hindered ketones using cyanide catalysis fails;20b enolizable ketones may form silyl enol ethers;19,20b and the b-(trimethylsilyloxy)nitriles derived from cyclic ketones undergo spontaneous elimination to give a,b-unsaturated nitriles.19

Related Reagents.

t-Butyl Trimethylsilylacetate; N,N-Dimethyl-2-(trimethylsilyl)acetamide; Ethyl Lithio(trimethylsilyl)acetate; Ethyl 2-(Methyldiphenylsilyl)propanoate; Ethyl Trimethylsilylacetate; Lithioacetonitrile.


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2. Ekouya, A.; Dunogues, J.; Duffaut, N.; Calas, R. JOM 1978, 148, 225 (CA 1978, 88, 190 961b).
3. Matsuda, I.; Murata, S.; Ishii, Y. JCS(P1) 1979, 26.
4. Kanemoto, N.; Inoue, S.; Sato, Y. SC 1987, 17, 1273.
5. Wells, G. J.; Yan, T.-H.; Paquette, L. A. JOC 1984, 49, 3604.
6. Haruta, R.; Ishiguro, M.; Furuta, K.; Mori, A.; Ikeda, N.; Yamamoto, H. CL 1982, 1093.
7. Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto, H. BCJ 1984, 57, 2768.
8. Mauzé, B.; Miginiac, L. SC 1990, 20, 2251.
9. Zimmerman, H. E.; Klun, R. T. T 1978, 34, 1775.
10. Ojima, I.; Kumagai, M. TL 1974, 15, 4005.
11. Tomioka, K.; Koga, K. TL 1984, 25, 1599.
12. Paquette, L. A.; Friedrich, D.; Pinard, E.; Williams, J. P.; St. Laurent, D.; Roden, B. A. JACS 1993, 115, 4377.
13. Tomioka, K.; Hagiwara, A.; Koga, K. TL 1988, 29, 3095.
14. Mauzé, B.; Miginiac, L. JOM 1991, 411, 69 (CA 1991, 115, 136 175m).
15. Inoue, S.; Sato, Y. OM 1986, 5, 1197.
16. Palomo, C.; Aizpurua, J. M.; García, J. M.; Ganboa, I.; Cossio, F. P.; Lecea, B.; Lopez, C. JOC 1990, 55, 2498.
17. Dembech, P.; Guerrini, A.; Ricci, A.; Seconi, G.; Taddei, M. T 1990, 46, 2999.
18. Nair, V.; Turner, G. A.; Buenger, G. S.; Chamberlain, S. D. JOC 1988, 53, 3051.
19. Palomo, C.; Aizpurua, J. M.; López, M. C.; Lecea, B. JCS(P1) 1989, 1692.
20. (a) Gostevskii, B. A.; Kruglaya, O. A.; Albanov, A. I.; Vyazankin, N. S. JOU 1979, 15, 983. (b) Gostevskii, B. A.; Kruglaya, O. A.; Albanov, A. I.; Vyazankin, N. S. JOM 1980, 187, 157.
21. Csuk, R.; Glänzer, B. I. J. Carbohydr. Chem. 1990, 9, 809.
22. Nicolaou, K. C.; Dolle, R. E.; Chucholowski, A.; Randall, J. L. CC 1984, 1153.

David Watt & Miroslaw Golinski

University of Kentucky, Lexington, KY, USA



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