Bis(trimethylsilyl)acetylene

[14630-40-1]  · C8H18Si2  · Bis(trimethylsilyl)acetylene  · (MW 170.40)

(nucleophile in Friedel-Crafts type acylations and alkylations; lithium trimethylsilylacetylide precursor; cycloaddition substrate)

Alternate Name: BTMSA.

Physical Data: mp 26 °C; bp 136-137 °C; d 0.752 g cm-3.

Solubility: sol all commonly used organic solvents.

Form Supplied in: clear liquid; widely available.

Preparative Method: from acetylene by treatment with n-Butyllithium followed by Chlorotrimethylsilane.1

Handling, Storage, and Precautions: the liquid is flammable and an irritant. Use in a fume hood.

Friedel-Crafts Alkylation/Acylation and Related Reactions.

Bis(trimethylsilyl)acetylene (BTMSA) can be added to a variety of Lewis acid-activated electrophiles. The most common variation which has been used in several total syntheses is the addition of BTMSA to acid chlorides in the presence of Aluminum Chloride to afford a,b-alkynic ketones in good yields (eq 1);2,3 this complements the method by which monosubstituted alkynes are added to carboxylic acid anhydrides, esters and tertiary amides (see n-Butyllithium-Boron Trifluoride Etherate). In addition to acid chlorides, BTMSA can be added to optically active acetals in the presence of Titanium(IV) Chloride to afford, after cleavage of the chiral template, a-hydroxyalkynes in excellent yield and high enantiopurity (eq 2).4 BTMSA can also be added to the oxonium ion intermediate resulting from the treatment of tri-O-acetyl-D-glucal with Tin(IV) Chloride to give the a-alkynylated pyranose in excellent yield as a single stereoisomer (eq 3).5 In a related example, it has been shown that BTMSA can be added to g-lactols in the presence of Boron Trifluoride Etherate to afford highly substituted tetrahydrofuran-3-carboxylates in high stereoselectivity.6

In addition, treatment of d-methoxyproline derivatives7 and g-methoxy-g-lactams8 under the Lewis acid/BTMSA conditions gives d-alkynic prolines and g-alkynic g-lactams, respectively. BTMSA will undergo a 1,4-addition to ethylenic acyl cyanides in the presence of TiCl4 to give g,d-alkynic acyl cyanides in good yield (eq 4).9 BTMSA will also add to tertiary10 or activated halides in the presence of Lewis acids (eq 5).11

Concerning noncarbon electrophiles, addition of BTMSA to arylsulfonyl chlorides in the presence of aluminum chloride affords ethynyl sulfones12 which have been used as Michael acceptors and Diels-Alder dienophiles.13 It is presumed that the Lewis acid catalyzed processes summarized above proceed via a silicon-stabilized vinyl cation, which then loses the trimethylsilyl moiety to afford the alkynic products.

Trimethylsilylacetylide Alkylation Reactions.

While BTMSA adds to a number of electrophiles under Lewis acid-catalyzed conditions, this reagent can also be used as a trimethylsilylacetylide precursor. In this regard, it has been reported that treatment of BTMSA with Methyllithium-LiBr complex in THF gives quantitative formation of lithium trimethylsilylacetylide (eq 6).14 The utility of this reagent lies in its ability to provide access to a diverse group of protected, terminal alkynes. For example, this reagent, which is formed in situ, can be added to aldehydes to give secondary a-hydroxy alkynes,14 ketones to afford tertiary a-hydroxy alkynes (eq 7),15 epoxides to form b-hydroxy alkynes,16 or alkyl halides to give monoalkylated alkynes.17 Lithium trimethylsilylacetylide can be brominated with Bromine and coupled with copper acetylides to give 1,3-diynes18 or iodinated with Iodine Monochloride19 and coupled with arylcopper reagents to afford aryl alkynes in good yields.20 This lithium acetylide intermediate has also been transmetalated with Zinc Bromide and coupled with a vinyl iodide in the presence of Pd0 to give a 1,3-enyne21 (eq 8) or with Diethylaluminum Chloride and coupled with an enone in the presence of a nickel catalyst to afford a g,d-alkynic ketone (eq 9).22

Cycloaddition Reactions.

BTMSA is a powerful substrate in a variety of cycloaddition reactions. The most common use of this reagent in that sense involves the transition metal-catalyzed [2 + 2 + 2] cycloaddition.23 BTMSA can be added to 1,5-hexadiyne in the presence of a cobalt catalyst to afford the highly strained, versatile synthetic intermediate 4,5-bis(trimethylsilyl)benzocyclobutene (eq 10).24 When this reaction is run on a diyne with a properly tethered vinyl group the initial adduct isomerizes to the corresponding o-xylylene and undergoes an intramolecular [4 + 2] cycloaddition to afford complex polycycles in high yields (eq 11);25 this method was used in a concise total synthesis of (±)-estrone.26 Varying the BTMSA acceptor in this reaction gives a number of polycyclic heterocycles including 2H-pyrans,27 2,3-dihydro-5(1H)-indolizinones,28 anthraquinones,29 tetrahydroisoquinolines (eq 12)30 and 1,3-diazabiphenylenes (eq 13).31

BTMSA can also be added to several dienes in Diels-Alder fashion. Pretreatment of hydrocarbon dienes such as 1,3-butadiene with catalytic Et2AlCl/TiCl4 followed by addition of BTMSA at 60 °C gives the corresponding bis(trimethylsilyl)cyclohexadienes in high yields.32 BTMSA can be added to a-pyrone in decalin at 165 °C to give 1,2-bis(trimethylsilyl)benzene in good yield,33 as well as to 6H-1,3-oxazin-6-ones in refluxing decalin to afford 3,4-bis(trimethylsilyl)pyridine in moderate yield.34 In addition, BTMSA can be added to 4-phenyloxazole in the presence of catalytic triethylamine at 250 °C to give 3,4-bis(trimethylsilyl)furan in excellent yield.35 BTMSA has also been used in other cycloadditions including cyclopropenation involving bis(methoxycarbonyl)carbene,36 [2 + 2] cycloaddition with dichloroketene to give silylated cyclobutenedione,37 1,3-dipolar cycloaddition with pyridinium dicyanomethylides to afford silylated indolizines,38 and with nitrile oxides to give isoxazoles.39

Miscellaneous Reactions.

In addition to BTMSA being used as an acetylide synthon, it can also be converted to the corresponding alkynyl(phenyl)iodonium tosylate40 and treated with nucleophiles such as 1,3-dicarbonyl compounds.41 1-Nitro-2-(trimethylsilyl)acetylene has been prepared from BTMSA and undergoes a series of cycloadditions analogous to BTMSA itself.42 In addition, BTMSA will undergo hydroboration with dialkylborane to afford 1-substituted 1,2-bis(trimethylsilyl)ethenes43 or with Borane-Dimethyl Sulfide to give an acylsilane.44 Finally, it was reported that BTMSA could be treated with cyclopropylcarbene-chromium complex to give silylated 3-methoxy-2-cyclopentenone in good yield.45

Related Reagents.

Trimethylsilylacetylene.


1. Walton, D. R. M.; Waugh, F. JOM 1972, 37, 45.
2. Treilhou, M.; Fauve, A.; Pougny, J.-R.; Prome, J.-C.; Veschambre, H. JOC 1992, 57, 3203.
3. For the conversion of the resulting a,b-alkynic ketones to a,b-unsaturated aldehydes, see: Newman, H. JOC 1973, 38, 2254.
4. Johnson, W. S.; Elliott, R.; Elliott, J. D. JACS 1983, 105, 2904. For a full procedural account of this method, see: Holmes, A. B.; Tabor, A. B.; Baker, R. JCS(P1) 1991, 3301. For an example of this type of addition with an acetal resulting from an unusual one-pot Beckmann fragmentation/acetalization, see: Fujioka, H.; Kitagawa, H.; Yamanaka, T.; Kita, Y. CPB 1992, 40, 3118.
5. (a) Tsukiyama, T.; Isobe, M. TL 1992, 33, 7911. (b) Ichikawa, Y.; Isobe, M.; Konobe, M.; Goto, T. Carbohydr. Res. 1987, 171, 193.
6. Bruckner, C.; Holzinger, H.; Reissig, H.-U. JOC 1988, 53, 2450.
7. Manfre, F.; Kern, J.-M.; Biellmann, J.-F. JOC 1992, 57, 2060.
8. Lundkvist, J. R. M.; Ringdahl, B.; Hacksell, U. JMC 1989, 32, 863.
9. Jellal, A.; Zahra, J.-P.; Santelli, M. TL 1983, 24, 1395.
10. Capozzi, G.; Romeo, G.; Marcuzzi, F. CC 1982, 959.
11. Casara, P.; Metcalf, B. W. TL 1978, 1581.
12. Bhattacharya, S. N.; Josiah, B. M.; Walton, D. R. M. Organomet. Org. Synth. 1971, 1, 145.
13. For the preparation of ethynyl p-tolyl sulfone using this method along with references regarding its use, see: Waykole, L.; Paquette, L. A. OS 1988, 67, 149.
14. Holmes, A. B.; Jennings-White, C. L. D.; Schulthess, A. H.; Akinde, B.; Walton, D. R. M. CC 1979, 840. For the preparation of dilithioacetylide from BTMSA, see: Ogawa, S.; Tajiri, Y.; Furukawa, N. TL 1993, 34, 839.
15. Takemoto, T.; Fukaya, C.; Yokoyama, K. TL 1989, 30, 723.
16. Negishi, E.; Boardman, L. D.; Sawada, H.; Bagheri, V.; Stoll, A. T.; Tour, J. M.; Rand, C. L. JACS 1988, 110, 5383.
17. Gorgen, G.; Boland, W.; Preiss, U.; Simon, H. HCA 1989, 72, 917.
18. Miller, J. A.; Zweifel, G. S 1983, 128.
19. (a) Walton, D. R. M.; Webb, M. J. JOM 1972, 37, 41. (b) Al-Hassan, M. I. JOM 1989, 372, 183.
20. Oliver, R.; Walton, D. R. M. TL 1972, 5209.
21. Alexakis, A.; Marek, I.; Mangeney, P.; Normant, J. F. T 1991, 47, 1677.
22. Aristoff, P. A.; Johnson, P. D.; Harrison, A. W. JOC 1983, 48, 5341.
23. For a review of this topic, see: Vollhardt, K. P. C. ACR 1977, 10, 1.
24. Aalbersberg, W. G. L.; Barkovich, A. J.; Funk, R. L.; Hillard III, R. L.; Vollhardt, K. P. C. JACS 1975, 97, 5600. For an example of this method in the synthesis of polycycles of theoretical interest, see: Schwager, H.; Spyroudis, S.; Vollhardt, K. P. C. JOM 1990, 382, 191.
25. Funk, R. L.; Vollhardt, K. P. C. JACS 1977, 99, 5483. For the full paper regarding this work, see: Funk, R. L.; Vollhardt, K. P. C. JACS 1980, 102, 5245.
26. Funk, R. L.; Vollhardt, K. P. C. JACS 1980, 102, 5253. For a synthesis of the phyllocladane diterpene skeleton using this methodology, see: Gotteland, J.-P.; Malacria, M. TL 1989, 30, 2541.
27. Harvey, D. F.; Johnson, B. M.; Ung, C. S.; Vollhardt, K. P. C. SL 1989, 15.
28. Earl, R. A.; Vollhardt, K. P. C. JOC 1984, 49, 4786.
29. Hillard III, R. L.; Vollhardt, K. P. C. JACS 1977, 99, 4058.
30. Hillard III, R. L.; Parnell, C. A.; Vollhardt, K. P. C. T 1983, 39, 905.
31. Bakthavachalam, V.; d'Alarcao, M.; Leonard, N. J. JOC 1984, 49, 289.
32. Mach, K.; Antropiusova, H.; Petrusova, L.; Turecek, F.; Hanus, V.; Sedmera, P.; Schraml, J. JOM 1985, 289, 331. For an example of a [6 + 2] cycloaddition involving BTMSA under these conditions, see: Mach, K.; Antropiusova, H.; Petrusovă, L.; Hanus, V.; Ture&cbreve;ek, F.; Sedmera, P. T 1984, 40, 3295.
33. Jones, P. R.; Albanesi, T. E.; Gillespie, R. D.; Jones, P. C.; Ng, S. W. Appl. Organomet. Chem. 1987, 1, 521.
34. Yamamoto, Y.; Morita, Y. H 1990, 30, 771.
35. Song, Z. Z.; Zhou, Z. Y.; Mak, T. C. W.; Wong, H. N. C. AG(E) 1993, 32, 432.
36. Wheeler, T. N.; Ray, J. JOC 1987, 52, 4875. Also see: Garratt, P. J.; Tsotinis, A. JOC 1990, 55, 84.
37. Zhao, D.-C.; Tidwell, T. T. JACS 1992, 114, 10980.
38. Ikemi, Y.; Matsumoto, K.; Uchida, T. H 1983, 20, 1009. Also see: Matsumoto, K.; Uchida, T.; Ikemi, Y.; Tanaka, T.; Asahi, M.; Kato, T.; Konishi, H. BCJ 1987, 60, 3645.
39. Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P. S 1987, 11, 998. Also see: Padwa, A.; MacDonald, J. G. JOC 1983, 48, 3189.
40. Stang, P. J.; Kitamura, T. OS 1991, 70, 215. For a review of this type of reagent, see: Stang, P. J. AG(E) 1992, 31, 274.
41. Bachi, M. D.; Bar-Ner, N.; Crittell, C. M.; Stang, P. J.; Williamson, B. L. JOC 1991, 56, 3912. Also see: Ochiai, M.; Ito, T.; Takaoka, Y.; Masaki, Y.; Kunishima, M.; Tani, S.; Nagao, Y. CC 1990, 118.
42. Bottaro, J. C.; Schmitt, R. J.; Bedford, C. D.; Gilardi, R.; George, C. JOC 1990, 55, 1916.
43. Hoshi, M.; Masuda, Y.; Arase, A. BCJ 1993, 66, 914.
44. Miller, J. A.; Zweifel, G. S 1981, 288.
45. Tumer, S. U.; Herndon, J. W.; McMullen, L. A. JACS 1992, 114, 8394. For a related example, see: Xu, Y.-C.; Wulff, W. D. JOC 1987, 52, 3263.

Michael L. Curtin

Abbott Laboratories, Abbott Park, IL, USA



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