1,3-Bis(triisopropylsilyl)propyne

[82192-59-4]  · C21H44Si2  · 1,3-Bis(triisopropylsilyl)propyne  · (MW 352.75)

(precursor of a stereoselective bulky C3 nucleophile, functionalized Peterson reagent1)

Alternate Name: 1,3-bis(TIPS)propyne.

Physical Data: bp 130-135 °C/0.08 mmHg; d 0.846 g cm-3.

Solubility: both the reagent and its lithio derivative are soluble in ether or THF.

Analysis of Reagent Purity: GC at 210 °C on a glass capillary column coated with OV-17; TLC on silica (hexanes, Rf 0.75). 1H NMR (CDCl3, 80 MHz): d = 1.63 (s, CH2), 1.3-0.9 (m, 2 TIPS).

Preparative Method: 1,3-bis(TIPS)propyne is prepared in quantitative yield by silylation of 3-Lithio-1-triisopropylsilyl-1-propyne with Triisopropylsilyl Trifluoromethanesulfonate.2

Purification: by distillation or chromatography.

Handling, Storage, and Precautions: no special precautions required; the reagent is not changed when stored for several months at ambient temperature. The Li derivative is handled under inert gas using simple syringe equipment.

Generation of Lithio-1,3-bis(triisopropylsilyl)propyne.

The main use of the title reagent is as a precursor of the lithium derivative. 1,3-Bis(triisopropylsilyl)propyne is cleanly lithiated by treatment with 1 equiv of n-Butyllithium in THF at -20 °C (15 min) to what is probably an equilibrium mixture of propargylic and allenic species (1) and (2) (eq 1).3 The bulky triisopropylsilyl (TIPS) group serves as a controlling group in the addition of (1/2) to electrophiles.

Formation of (Z)-enynes.

The lithio derivative reacts with aliphatic aldehydes (RCHO, -78 °C -> rt, few h) to form the (Z)-enynes R-CH=CH-C&tbond;C-TIPS (3) in good yield (57-79%) and high isomeric purity (Z:E &AApprox; 20:1, eq 2). The intermediate addition product formed by attack of (2) on the aldehyde has erythro configuration2 and undergoes syn elimination of silanolate to give (3) by the pathway generally observed in Peterson reactions in alkaline media.4

The method was used for attachment of the cis enyne side chain in a synthesis of gephyrotoxin,5 and for the preparation of (Z)-non-3-en-1-yne, a building block in the synthesis of prostaglandins and of 11-HETE methyl ester.6

Formation of (E)-Enynes.

The stereoselectivity of the reaction can be reversed simply by adding 5 equiv Hexamethylphosphoric Triamide to the solution of (1/2) prior to addition of the aldehyde. Under these conditions the reaction is complete within a few seconds at -78 °C, and (E)-enynes (4) are isolated in 60-65% yield with high E:Z selectivity (20:1 to 10:1, eq 3). Evidence has been presented that the action of HMPA is exerted in the addition to the aldehyde, not in the elimination step.2 A threo propargylic intermediate is presumably formed by attack of an ion pair similar to (1) onto the aldehyde. The method was used for the introduction of the trans enyne side chain in a synthesis of laurenyne.7

The stereochemical preferences of these reactions are less pronounced with aromatic aldehydes. For example, the reaction of (1/2) with benzaldehyde in THF gives a 2:1 mixture of Z:E enynes (-20 -> 0 °C, 1 h, 67%), whereas in the presence of 1 equiv HMPA mostly the (E)-enyne is obtained (1:9 selectivity, -78 °C, 10 s, 78%).

Enynes and Dienynes from Other Bis(silyl)propynes.

Corresponding Li reagents containing a less bulky silyl group at the propargylic carbon generally show lower selectivity for (Z)-enynes, e.g. the Li derivatives of 1,3-bis(trimethylsilyl)propyne, 1-trimethylsilyl-3-triethylsilyl-1-propyne, 1-trimethylsilyl-3-t-butyldimethylsilyl-1-propyne (TMS-C&tbond;C-CH2-SiR3 with R3 = Me3, Et3, t-BuMe2).8 Selectivity could be improved by using a Mg or Ti counterion instead of Li.8-10 Cinnamaldehyde, cyclohexanone, and cis- and trans-hydrindanones11 likewise underwent the reaction.

1-Trimethylsilyl-3-triisopropylsilyl-1-propyne (TMS-C&tbond;C-CH2-TIPS, 5) was found to give essentially the same results (yield and stereoselectivity) as bis(TIPS)propyne in two cases of direct comparison (crotonaldehyde, cinnamaldehyde).12 Scrambling of the silyl groups did not occur. Compound (5) is available from TMS-C&tbond;C-CH2Br by reaction with Magnesium in the presence of 0.5% Mercury(II) Chloride followed by silylation with TIPS-OTf (76%). Silane (5) can also be prepared from propargyl bromide by reaction with (1) Mg/0.5% HgCl2, (2) TIPS-OTf, (3) n-BuLi, (4) TMS-Cl (two-pot procedure, 63% overall).12

Using the lithio reagent obtained from (5) in THF, (Z)-dienynes were prepared in good yield and stereoselectivity from several a,b-unsaturated aldehydes (eq 4) (Table 1).12,13 In the corresponding Wittig reactions, the yields and isomeric purity of enynes were far lower. Oxirane and aziridine groups are compatible with the reaction conditions (eq 5) (Table 2).12

The preparation of (Z)-enynes by alternative methods (Wittig-Horner and others) is possible;14-16 and is also possible for (E)-enynes (Wittig).17-19

Epoxide Opening.

The lithio propyne derivative (1/2) adds to epoxides in spite of its bulkiness. The TIPS group near the reaction center is useful for preventing secondary reactions in a polyepoxide substrate. Thus while the simple monoadduct (6a) from cis-benzene trioxide and 3-lithio-1-TIPS-1-propyne was formed as a minor product only (always accompanied by products (7a), (8a), (9a)), the monoadduct (6b) was isolated in 48% yield (two diastereomers) from the reaction with (1/2) along with 10% (7b); bisadducts (8b/9b) were not formed (eq 6).20


1. FF 11, 63.
2. Corey, E. J., Rücker, Ch. TL 1982, 23, 719.
3. Peterson, P. E.; Jensen, B. L. TL 1984, 25, 5711.
4. (a) Ager, D. J. S 1984, 384. (b) Ager, D. J. OR 1990, 38, 1.
5. Overman, L. E.; Lesuisse, D.; Hashimoto, M. JACS 1983, 105, 5373.
6. (a) Corey, E. J.; Shimoji, K.; Shih, C. JACS 1984, 106, 6425. (b) Corey, E. J.; Shih, C.; Shih, N.-Y.; Shimoji, K. TL 1984, 25, 5013.
7. Overman, L. E.; Thompson, A. S. JACS 1988, 110, 2248.
8. Yamakado, Y.; Ishiguro, M.; Ikeda, N.; Yamamoto, H. JACS 1981, 103, 5568.
9. Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto, H. BCJ 1984, 57, 2768.
10. Palazón, J. M.; Martín, V. S. TL 1988, 29, 681.
11. Peterson, P. E.; Leffew, R. L. B.; Jensen, B. L. JOC 1986, 51, 1948.
12. Schulz, D. Diploma Thesis, Universität Freiburg, 1985.
13. (a) Eberbach, W.; Laber, N. TL 1992, 33, 57. (b) Laber, N. Thesis, Universität Freiburg, 1991.
14. Gao, L.; Murai, A. TL 1992, 33, 4349.
15. Holmes, A. B.; Pooley, G. R. T 1992, 48, 7775.
16. Gibson, A. W.; Humphrey, G. R.; Kennedy, D. J.; Wright, S. H. B. S 1991, 414.
17. (a) Marshall, J. A.; Grote, J.; Shearer, B. JOC 1986, 51, 1633. (b) Marshall, J. A.; Salovich, J. M.; Shearer, B. G. JOC 1990, 55, 2398.
18. (a) Luh, T.-Y.; Wong, K.-T. S 1993, 349. (b) Stadnichuk, M. D.; Voropaeva, T. I. RCR 1992, 61, 1091.
19. Wang, K. K.; Wang, Z.; Gu, Y. G. TL 1993, 34, 8391.
20. Rücker, Ch. unpublished results.

Christoph Rücker

Universität Freiburg, Germany



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