[82192-58-3]  · C12H23LiSi  · 3-Lithio-1-triisopropylsilyl-1-propyne  · (MW 202.38)

(functionalized nucleophilic C3 building block; forms C-C bonds with many carbon electrophiles1)

Alternate Name: 3-triisopropylsilyl-2-propynyllithium.

Physical Data: (precursor) bp 100-101 °C/5 mmHg; d 0.813 g cm-3.

Solubility: good sol ether, THF.


The title reagent (1) was conceived as an improved version of TMS-C&tbond;C-CH2Li.2,3 The bulky triisopropylsilyl (TIPS) group provides efficient screening of the carbon atom to which it is attached, and (1) therefore usually forms propargylic rather than allenic products.2,4 The TIPS group is much more inert in basic and nucleophilic reaction mixtures than the widely used TMS group. At the same time, TIPS (in contrast to tri-t-butylsilyl) is commercially available, easily introduced, and readily cleaved (F-) from the product.

Reagent (1) is made by deprotonation of 1-TIPS-propyne2 using n-Butyllithium in ether, better without than with TMEDA added,5 or t-Butyllithium in ether/pentane, or preferably n-BuLi in THF (-20 °C, 15 min). 1-TIPS-propyne can be prepared from propyne by silylation of either its lithio derivative using TIPS triflate2 or of the bromomagnesium derivative using TIPS chloride;6 it is also commercially available.

Homopropargylic Alcohols.

Reagent (1) smoothly reacts with aldehydes and ketones (eqs 1-3).2,7

The reaction in eq 1, when performed in ether, gave rise to a 2:1 mixture of the same products. The TMS analog gave none of the corresponding adducts at all in ether/HMPA; in ether it produced both allenic and propargylic major products.

Conjugate Addition.

Reagent (1) in THF adds in 1,2-fashion to a,b-unsaturated ketones, whereas in THF/HMPA, 1,4-addition is observed as result of kinetic control (eq 4).2 The hindered a,b-unsaturated ketone isophorone gave smooth 1,2-addition in THF (89%), while in THF/HMPA, 1,2- and 1,4-addition occurred (1:1) in low conversion. 1,2-Addition of (1) to Acrolein afforded a building block for bongkrekic acid.8a 1,4-Addition of (1) to h4-(dienyl)Fe(CO)3 substituted alkylidene malonates is highly stereoselective.8b

Reactions of similar organoalkynyl/allenyl silanes containing various metals with carbonyl compounds to give propargylic products have been reported.9-11 Conjugate addition of allenyl stannanes to a,b-unsaturated carbonyl compounds to give propargylic products can be effected in the presence of Titanium(IV) Chloride.12

Chain Elongation of Activated Halides or Phospates.

Reagent (1) displaces halide ion from benzyl and allyl halides (eqs 5 and 6).2 The TMS analog reacted less selectively and gave lower yields.13

This type of coupling was routinely used by Marshall (allyl chlorides or phosphates) in the synthesis of cembranoids, employing a cuprate made from the bromomagnesium analog TIPS-C&tbond;C-CH2MgBr (2), which is prepared from TIPS-C&tbond;C-CH2Br.14 As a rule, with these allylic electrophiles, SN2 reaction is not observed. An OH function does not interfere if protected as its bromomagnesium salt,14g silyl ether,14c,d or even acetate.14e,g

Epoxide Opening and Cyclopropane Formation.

Reagent (1) cleanly opens epoxides (eq 7; SN2).2

In vinyl epoxides, both exclusive SN2 and exclusive SN2 reactions were observed for similar reagents, depending on the substrate (eqs 8 and 9).5,14a,b In eq 9, the TMS analog gives a mixture of propargylic and allenic products.

The products of epoxide opening by (1) can be transformed into cyclopropanes (eq 10). The TMS analog gave 75% in the cyclization step.

This method was triply used in the preparation of a carbocyclic cis-tris-s-homobenzene (eq 11).15

The triple epoxide opening gave higher yields (up to 67%) when organocuprates were used.16,17 The TMS analog of this tris adduct could not be obtained, due to uncontrolled desilylation reactions.

Transformations of the C&tbond;C-TIPS Group.

The C&tbond;C-TIPS group is cleaved by the action of various fluoride reagents, but not by the AgNO3/KCN procedure employed for cleavage of C&tbond;C-TMS. Corey and Rücker describe other useful transformations.2 The deprotected propargyl group may be further degraded to an acetic acid moiety by decarboxylative oxidation using RuO2/NaIO4 in CCl4/MeCN/H2O, as in the preparation of cis-tris-s-homobenzenes (eq 12).17

Oxidation of the products by Ruthenium(VIII) Oxide with the TIPS group still in place gives a mixture of carboxylic acid and an a-keto acyl silane (silyl a-diketone; (eq 13),7 an otherwise rare class of compounds;18 compare the oxidation of disubstituted alkynes to 1,2-diketones by RuO419 and the Osmium Tetroxide-t-Butyl Hydroperoxide oxidation of TMS-alkynes.20

TMS-alkynes are oxidized at the terminal carbon to carboxylic acids by hydroboration/oxidation (dicyclohexylborane/NaOH, H2O2). This does not work with TIPS-alkynes.14b Instead, TIPS-alkynes are cleanly monohydroborated at the internal carbon by 9-Borabicyclo[3.3.1]nonane to give (Z)-b-borylvinylsilanes.6 These can be oxidized in high yields to a-silyl ketones, or cross coupled with a bromide R1Br (R1 = aryl, benzyl, dimethylvinyl) in the presence of NaOH and Tetrakis(triphenylphosphine)palladium(0) to give b,b-disubstituted vinylsilanes (Suzuki reaction; eq 14).21a The same nucleophilic substituted vinylsilane can be added to an aromatic aldehyde to provide access to (E)-3-silyl allyl alcohols.21b

Propargyl Ketones.

The cyanocuprate derived from (1) reacts with esters to form propargyl ketones, even in the presence of epoxide functionality (eq 15).16


Reaction of (1) with silylating agents affords 1,3-bis(silyl)propynes, valuable Peterson reagents (eq 16) (see 1,3-Bis(triisopropylsilyl)propyne).2

Isomeric Species.

The isomeric substituted lithium acetylide LiC&tbond;C-CH2TIPS (4), from 3-TIPS-propyne,22 was silylated to 1-TMS-3-TIPS-propyne.23 Compound (4) isomerizes to (1) in THF/HMPA solution at rt, as shown by isolation of pure 1-TIPS-propyne after quenching a solution of (4) with H2O.7

1. FF 1984, 11, 566.
2. Corey, E. J.; Rücker, Ch. TL 1982, 23, 719.
3. Stowell, J. C. CRV 1984, 84, 409.
4. Furuta, K.; Ishiguro, M.; Haruta, R.; Ikeda, N.; Yamamoto, H. BCJ 1984, 57, 2768.
5. Stork, G.; Kowalski, C.; Garcia, G. JACS 1975, 97, 3258.
6. Soderquist, J. A.; Colberg, J. C.; Del Valle, L. JACS 1989, 111, 4873.
7. Rücker, Ch. unpublished results.
8. (a) Corey, E. J.; Tramontano, A. JACS 1984, 106, 462. (b) Wada, C. K.; Roush, W. R. TL 1994, 35, 7351.
9. (a) Mesnard, D.; Miginiac, L. JOM 1990, 397, 127. (b) Suzuki, M.; Morita, Y.; Noyori, R. JOC 1990, 55, 441.
10. Zhang, L.-J.; Mo, X.-S.; Huang, J.-L.; Huang, Y.-Z. TL 1993, 34, 1621.
11. (a) Danheiser, R. L.; Carini, D. J.; Kwasigroch, C. A. JOC 1986, 51, 3870. (b) Brown, H. C.; Khire, U. R.; Racherla, U. S. TL 1993, 34, 15.
12. Haruta, J.; Nishi, K.; Matsuda, S.; Akai, S.; Tamura, Y.; Kita, Y. JOC 1990, 55, 4853.
13. (a) Corey, E. J.; Kirst, H. A. TL 1968, 5041. (b) Kirst, H. A. Ph.D. Thesis, Harvard University, 1971.
14. (a) Marshall, J. A.; Peterson, J. C.; Lebioda, L. JACS 1983, 105, 6515. (b) Marshall, J. A.; Peterson, J. C.; Lebioda, L. JACS 1984, 106, 6006. (c) Marshall, J. A.; Jenson, T. M.; DeHoff, B. S. JOC 1987, 52, 3860. (d) Marshall, J. A.; Lebreton, J.; DeHoff, B. S.; Jenson, T. M. JOC 1987, 52, 3883. (e) Marshall, J. A.; DeHoff, B. S.; Crooks, S. L. TL 1987, 28, 527. (f) Marshall, J. A.; Lebreton, J.; DeHoff, B. S.; Jenson, T. M. TL 1987, 28, 723. (g) Marshall, J. A.; Crooks, S. L.; DeHoff, B. S. JOC 1988, 53, 1616. (h) Marshall, J. A.; Gung, W. Y. TL 1989, 30, 309. (i) Marshall, J. A.; Andersen, M. W. JOC 1992, 57, 2766.
15. Rücker, Ch.; Prinzbach, H. TL 1983, 24, 4099.
16. Braschwitz, W.-D. Ph.D. Thesis, Universität Freiburg, 1990.
17. Braschwitz, W.-D.; Otten, T.; Rücker, Ch.; Fritz, H.; Prinzbach, H. AG 1989, 101, 1383 (AG(E) 1989, 28, 1348).
18. Reich, H. J.; Kelly, M. J.; Olson, R. E.; Holtan, R. C. T 1983, 39, 949.
19. Gopal, H.; Gordon, A. J. TL 1971, 2941.
20. Page, P. C. B.; Rosenthal, S. TL 1986, 27, 1947.
21. (a) Soderquist, J. A.; Colberg, J. C. SL 1989, 25. (b) Soderquist, J. A.; Vaquer, J. TL 1990, 31, 4545.
22. Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. JOC 1992, 57, 6094.
23. Schulz, D. Diplom Thesis, Universität Freiburg, 1985.

Christoph Rücker

Universität Freiburg, Germany

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