Lithium (Trimethylsilyl)acetylide

Me3SiC&tbond;CLi

[54655-07-1]  · C5H9LiSi  · Lithium (Trimethylsilyl)acetylide  · (MW 104.17)

(synthesis of unsymmetrically disubstituted alkynes, where use of the silyl protecting group ensures selective monofunctionalization of the acetylide anion; the reaction products can be deprotected by cleavage of the Si-C bond, or the silicon group can be displaced with other electrophiles)

Form Supplied in: solution in THF (0.5 M).

Preparative Methods: most often prepared in situ by treatment of Trimethylsilylacetylene1 with n-Butyllithium,2 Lithium Diisopropylamide,3 or Ethyllithium-Lithium Bromide.4 It can also be prepared by monodesilylation of Bis(trimethylsilyl)acetylene with MeLi-LiBr complex (see Methyllithium).5

Transmetalation.

Lithium (trimethylsilyl)acetylide can be transmetalated to enhance reactivity. Reaction with CuBr.SMe2 (see Copper(I) Bromide) provides the lithium (trialkynyl)cuprate, which can undergo electrophilic amination to provide 1-alkynylamines.6 Transmetalation to cerium using Cerium(III) Chloride allows superior yields of addition products with cyclic ketones (eq 1).7,8

Addition to Carbonyl Compounds.

The title compound reacts with a variety of aldehydes5,9-12 and ketones13,14 to provide propargylic alcohol derivatives. Other carbonyl compounds used as substrates include quinones2a and quinone monoacetals,15 alkynyl aldehydes16 and ketones,17 and dialkyl squarates (eq 2).18 The propargylic alcohol products can be stereospecifically reduced to (E)-vinylsilanes, with Sodium Bis(2-methoxyethoxy)aluminum Hydride (Red-Al®).19

The reagent has been added to a-chiral aldehydes20,21 and ketones,22-25 with moderate to good stereoselectivity, although in one case the Grignard reagent proved superior to the lithium acetylide.23a Alternatively, optical activity can be introduced by employing a chiral ligand.26

Addition to Epoxides.

Lithium (trimethylsilyl)acetylide has been used to open terminal epoxides in the presence of Lewis acids such as GaMe327 or Boron Trifluoride Etherate (eq 3).28

Alkynyl Ketones.

Treatment of a Weinreb amide29 (see N,O-Dimethylhydroxylamine) or an isoxazolidide30 with the title compound provides good to excellent yields of a,b-ynones (eq 4).

Miscellaneous.

Lithium (trimethylsilyl)acetylide has been employed in the nucleophilic displacement of bromides10 and iodides31 and the Grignard analog in aryl chloride substitution.32 The reaction of lithium (trimethylsilyl)acetylide with 2-chloroethyl thiocyanate is an efficient route to 1-vinylthioacetylene.33 Trisubstituted vinylsilanes can be prepared from the reaction of lithium (trimethylsilyl)acetylide with trialkylboranes and electrophiles.34 The title reagent has been added to N-acyl imines to form a,a-disubstituted amino acid bis-amides.35 Excellent stereocontrol has been observed in addition reactions of lithium (trimethylsilyl)acetylide to 3-thiazolines (eq 5)3 and b-aminocyclopentenyl sulfones (eq 6).36

Related Reagents.

Dilithium Acetylide; Ethynylmagnesium Bromide; Lithium Acetylide; Lithium Chloroacetylide; Propynyllithium.


1. (a) Brandsma, L. Preparative Acetylenic Chemistry, 2nd ed.; Elsevier: Amsterdam, 1988; pp 114-116. (b) Holmes, A. B.; Sporikou, C. N. OS 1987, 65, 61. (c) Brandsma, L.; Verkruijsse, H. D. Synthesis of Acetylenes, Allenes, and Cumulenes; Elsevier: Amsterdam, 1981; pp 55-56.
2. (a) Chow, K.; Moore, H. W. JOC 1990, 55, 370. (b) Ref 1(c); pp 60-61.
3. Meltz, C. N.; Volkmann, R. A. TL 1983, 24, 4503.
4. Ref 1(a); pp 102-103.
5. Holmes, A. B.; Jennings-White, C. L. D.; Schulthess, A. H. CC 1979, 840.
6. Boche, G.; Bernheim, M.; Niessner, M. AG(E) 1983, 22, 53.
7. Tamura, Y.; Akai, S.; Kishimoto, H.; Sasho, M.; Kirihara, M.; Kita, Y. CPB 1988, 36, 3897.
8. The reaction shown in eq 1 was incomplete (49%) when run with lithium (trimethylsilyl)acetylide; Suzuki, M.; Kimura, Y.; Terashima, S. CL 1984, 1543.
9. Exon, C.; Magnus, P. JACS 1983, 105, 2477.
10. Trost, B. M.; Matsubara, S.; Caringi, J. J. JACS 1989, 111, 8745.
11. Toyota, M.; Terashima, S. TL 1989, 30, 829.
12. Taylor, E. C.; Goswami, S. TL 1991, 32, 7357.
13. Corey, E. J.; Wess, G.; Xiang, Y. B.; Singh, A. K. JACS 1987, 109, 4717.
14. Eguci, S.; Ikemoto, T.; Kobayakawa, Y.; Sasaki, T. CC 1985, 958.
15. Stern, A. J.; Swenton, J. S. CC 1988, 1255.
16. Wadsworth, D. H.; Geer, S. M.; Detty, M. R. JOC 1987, 52, 3662.
17. Alberts, A. H.; Wynberg, H. CC 1988, 748.
18. (a) Reed, M. W.; Moore, H. W. JOC 1987, 52, 3491. (b) Reed, M. W.; Pollart, D. J.; Perri, S. T.; Foland, L. D.; Moore, H. W. JOC 1988, 53, 2477.
19. Jones, T. K.; Denmark, S. E. OS 1984, 64, 182.
20. Lewis, M. D.; Duffy, J. P.; Heck, J. V.; Menes, R. TL 1988, 29, 2279.
21. Guanti, G.; Banfi, L.; Narisano, E. TL 1989, 30, 5511.
22. Nakatani, K.; Arai, K.; Hirayama, N.; Matsuda, F.; Terashima, S. TL 1990, 31, 2323.
23. (a) Tamura, Y.; Ko, T.; Kondo, H.; Annoura, H.; Fuji, M.; Takeuchi, R.; Fujioka, H. TL 1986, 27, 2117. (b) Tamura, Y.; Annoura, H.; Fuji, M.; Yoshida, T.; Takeuchi, R.; Fujioka, H. CPB 1987, 35, 4736.
24. Blazejewski, J. C.; Haddad, M.; Wakselman, C. TL 1992, 33, 1269.
25. White, J. D.; Somers, T. C.; Yager, K. M. TL 1990, 31, 59.
26. (a) Mukaiyama, T.; Suzuki, K.; Soai, K.; Sato, T. CL 1979, 447. (b) Mukaiyama, T.; Suzuki, K. CL 1980, 255.
27. Utimoto, K.; Lambert, C.; Fukuda, Y.; Shiragami, H.; Nozaki, H. TL 1984, 25, 5423.
28. Magnus, P.; Becker, D. P. JACS 1987, 109, 7495.
29. Jacobi, P. A.; Blum, C. A.; DeSimone, R. W.; Udodong, U. E. S. JACS 1991, 113, 5384; TL 1989, 30, 7173.
30. Cupps, T. L.; Boutin, R. H.; Rapoport, H. JOC 1985, 50, 3972.
31. Curran, D. P.; Rakiewicz, D. M. JACS 1985, 107, 1448.
32. Katz, H. E. JOC 1989, 54, 2179.
33. Verboom, W.; Meijer, J.; Brandsma, L. S 1978, 577.
34. Colvin, E. Silicon in Organic Synthesis; Butterworths: London, 1981; p 53.
35. Lipshutz, B. H.; Huff, B.; Vaccaro, W. TL 1986, 27, 4241.
36. Hutchinson, D. K.; Fuchs, P. L. JACS 1985, 107, 6137.

Mary Ann M. Fuhry

University of Cambridge, UK



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