Dimethylphenylsilyllithium1

PhMe2SiLi

[3839-31-4]  · C8H11LiSi  · Dimethylphenylsilyllithium  · (MW 142.22)

(reagent for addition to carbonyl compounds;2 deoxygenation reactions;3,4 in presence of copper(I) salts, an effective reagent for conjugate addition to a,b-unsaturated compounds,5 conjugate displacement of tertiary allylic acetates,6,7 and silylcupration of alkynes8 and allenes9)

Physical Data: NMR studies have shown the reagent is monomeric in ether.10c

Solubility: sol THF, Et2O.

Preparative Methods: readily prepared from the reaction of PhMe2SiCl with 2 equiv of Li metal in THF or from the reaction of PhMe2SiSiMe2Ph with Li metal in THF.10a,b Typical reaction procedure involves stirring Chlorodimethylphenylsilane with Lithium in THF at -8 °C under N2 for 36 h.8a The supernatant reagent solution is calibrated using standard methods and used without further purification for reactions.8a It is advantageous to activate the Li metal prior to use by ultrasound irradiation of a hexane suspension,11a and to use argon as the inert gas to prevent formation of lithium nitrides.11b

Handling, Storage, and Precautions: the reagent solution in THF can be stored under argon or nitrogen at -20 °C for several weeks without significant degradation.8a Lithium is a highly flammable solid and must be handled and stored in an inert atmosphere (preferably argon).

Addition to Carbonyl Compounds.

PhMe2SiLi in THF undergoes addition to aldehydes and ketones under mild conditions to afford a-silyl alcohols upon aqueous workup. The a-silyl alcohols are versatile synthetic intermediates which can be readily manipulated into a variety of products. Consequently, these reactions have been widely utilized in organic syntheses,12-15 for example in the synthesis of cytochalasin D cycloundecanone ring system (eq 1),12 and in the synthesis of (±)-pregn-4-en-20-one.13 Enones react with PhMe2SiLi predominantly via 1,2-addition to afford a-silyl alcohols which can be converted to silyl enol ethers via Brook rearrangement (eq 2).15

Addition of PhMe2SiLi to a-phenylthio ketones directly affords silyl enol ethers with very high (Z)-stereoselectivity (eq 3).16

Addition of PhMe2SiLi to aldehydes and subsequent O-sulfonylation of the generated alkoxides with p-Toluenesulfonyl Chloride affords a-silyl tosylates in good yields.2 Conversion of these intermediates into a-silyl selenocyanates followed by fluoride-induced cyanide elimination reaction permitted the synthesis and study of reactivity of previously unknown selenoaldehydes (eq 4).2

Deoxygenation Reactions.

PhMe2SiLi reacts with oxabicyclo[2.2.1]heptenes in Et2O at 0 °C to afford 1,3-cyclohexadienes (eq 5).3 6-8 equiv of PhMe2SiLi are required for complete consumption of the starting bicyclic compound. The excess stoichiometry sometimes leads to further reaction of the 1,3-cyclohexadiene product with the unreacted reagent. Use of the silylcuprate reagent PhMe2SiCu.LiCN in THF at 0 °C alleviates this problem.3

Epoxides are stereospecifically deoxygenated to alkenes with inversion of stereochemistry upon treatment with PhMe2SiLi in THF.4 trans-Stilbene is obtained in 83% yield and >99% stereoselectivity from the reaction of oxide of cis-stilbene with PhMe2SiLi. Similarly, trans-stilbene oxide is converted to cis-stilbene.

Reactions via Cuprates.

Dimethylphenylsilylcuprates [(PhMe2Si)2CuLi.LiX] (X = CN or halide), generated in situ from the reaction of 2 equiv of PhMe2SiLi with copper(I) salts (Copper(I) Cyanide, Copper(I) Iodide), are popular reagents for the incorporation of PhMe2Si unit into organic molecules.5-9,17 In general, these reagents react with substrates under milder conditions and tolerate polar functional groups better than PhMe2SiLi. However, these reagents suffer from one major drawback in that not all the Si anions bound to copper are transferred to the substrate. Consequently, reaction workup affords nonvolatile byproducts which complicate product isolation.5-9 This problem can be avoided by using the mixed cuprate (PhMe2Si)MeCuLi, prepared from the reaction of 1 equiv of PhMe2SiLi and 1 equiv of MeLi with CuCN.18 The mixed cuprate specifically transfers the silyl group (not the methyl group) to the substrate and exhibits reactivity comparable to that of Lithium Bis[dimethyl(phenyl)silyl]cuprate. Synthetically useful reactions of dimethylphenylsilylcuprates include addition to saturated aldehydes, 1,4-addition to a,b-unsaturated enones, conjugate displacement of tertiary allylic acetates, and silylcupration of alkynes and allenes.

The addition of (PhMe2Si)2CuLi to aldehydes has been utilized in the elegant synthesis of isocarbacyclin (eq 6).19

(PhMe2Si)2CuLi undergoes 1,4- (conjugate) addition to a variety of cyclic and acyclic a,b-unsaturated enones to afford saturated b-silyl carbonyl compounds (eq 7).5,20-22 In acyclic systems, enones can be regenerated from the b-silyl carbonyl compounds by bromination (Bromine-CCl4) followed by desilylbromination (Sodium Fluoride-EtOH).22 In cyclic systems, treatment of the b-silyl carbonyl compounds with Copper(II) Bromide affords the enones directly (eq 7).20 This overall silylation-desilylation protocol not only represents a method for the protection of a,b-unsaturation but can also be used advantageously by alkylating the intermediate enolate of conjugate silyl addition prior to desilylation (eq 7). This methodology has been successfully applied in the synthesis of carvone and dihydrojasmone.5a The alkylation of intermediate enolates is highly diastereoselective, favoring the isomer in which the silyl group and the alkyl group are in anti orientation (eq 8). The silyl functionality of the b-silyl carbonyl compounds also can be converted into a hydroxy group with retention of configuration (eq 8).5b

(PhMe2Si)2CuLi reacts with allylic acetates via stereospecific (anti) conjugate displacement of the acetate group to afford allylsilanes in excellent yields.7,23 Similar stereospecificity is observed in reactions with propargyl acetates.7a

(PhMe2Si)2CuLi reacts with alkynes via syn addition of the silyl group and copper to the carbon-carbon triple bond.8 In reactions with terminal alkynes, the silyl group becomes attached predominantly to the terminal carbon. The acidic hydrogen of terminal alkynes does not get abstracted under the reaction conditions. The vinylcuprate intermediates react with electrophiles including alkyl/acyl halides, iodine, epoxides, and enones to regio/stereoselectively afford a variety of vinylsilanes.8

Silylcupration of allene with (PhMe2Si)2CuLi followed by treatment of the intermediate cuprate with H+, carbon electrophiles, and Cl2 affords the corresponding vinylsilanes (eq 9).9 However, reaction of the intermediate cuprate with I2 affords an allylsilane, from which other more highly substituted allylsilanes are readily obtainable (eq 9). In reaction with substituted allenes, the product ratio (vinylsilane vs. allylsilane) is dependent upon the degree of substitution.9

Related Reactions.

In contrast to PhMe2SiLi, related R3SiLi reagents either are appreciably less stable, may require generation in toxic solvents (Hexamethylphosphoric Triamide), and can be less nucleophilic, favoring deprotonation or electron transfer reactions. Nevertheless, complementary synthetic organic transformations have been described for these reagents,24 for example the 1,4-addition of Trimethylsilyllithium to enones25 and the reduction of isocyanates to isocyanides with t-BuPh2SiLi.26 The wide synthetic utility of PhMe2SiLi and (PhMe2Si)2CuLi in organic synthesis has also encouraged the development and use of related PhMe2Si- derivatives of Al,27 Mg,28 Mn,28 and Zn.27a,29

Related Reagents.

Dimethylphenylsilyl(methyl)magnesium; Lithium Bis[dimethyl(phenyl)silyl]cuprate; Trimethylsilylcopper; Trimethylsilyllithium.


1. (a) Colvin, E. W. Silicon in Organic Synthesis; Butterworths: London, 1981; pp 134-140. (b) Fleming, I. CSR 1981, 10, 83.
2. (a) Krafft, G. A.; Meinke, P. T. JACS 1986, 108, 1314. (b) Krafft, G. A.; Meinke, P. T. JACS 1988, 110, 8671.
3. Lautens, M.; Ma, S.; Belter, R. K.; Chiu, P.; Leschziner, A. JOC 1992, 57, 4065.
4. Reetz, M. T.; Plachky, M. S 1976, 199.
5. (a) Ager, D. J.; Fleming, I.; Patel, S. K. JCS(P1) 1981, 2520. (b) Fleming, I.; Henning, R.; Plaut, H. CC 1984, 29.
6. (a) Fleming, I.; Marchi, D., Jr. S 1981, 560. (b) Fleming, I.; Higgins, D. JCS(P1) 1989, 206.
7. (a) Fleming, I.; Terrett, N. K. JOM 1984, 264, 99. (b) Fleming, I.; Terrett, N. K. TL 1984, 25, 5103.
8. (a) Fleming, I.; Newton, T. W.; Roessler, F. JCS(P1) 1981, 2527. (b) Fleming, I.; Roessler, F. CC 1980, 276.
9. (a) Fleming, I.; Landais, Y.; Raithby, P. R. JCS(P1) 1991, 715. (b) Fleming, I.; Rowley, M.; Cuadrado, P.; Gonzalez-Nogal, A. M.; Pulido, F. J. T 1989, 45, 413.
10. (a) George, M. V.; Peterson, D. J.; Gilman, H. JACS 1960, 82, 403. (b) Gilman, H.; Lichtenwalter, G. D. JACS 1958, 80, 608. (c) Edlund, U.; Lejon, T.; Venkatachalan, T. K.; Buncel, E.; JACS 1985, 107, 6408.
11. (a) Asao, K.; Iio, H.; Tokoroyama, T. S 1990, 382. (b) Meinke, P. T. Ph.D. Thesis, Syracuse University, August 1987, p 35.
12. Vedejs, E.; Arnost, M. J.; Eustache, J. M.; Krafft, G. A. JOC 1982, 47, 4384.
13. Bishop, P. M.; Pearson, J. R.; Sutherland, J. K. CC 1983, 123.
14. (a) Barrett, A. G. M.; Hill, J. M.; Wallace, E. M. JOC 1992, 57, 386. (b) Burke, S. D.; Saunders, J. O.; Oplinger, J. A.; Murtiashaw, C. W. TL 1985, 26, 1131.
15. Koreeda, M.; Koo, S. TL 1990, 31, 831.
16. Reich, H. J.; Holtan, R. C.; Bolm, C. JACS 1990, 112, 5609. Also see ref. 12.
17. Proposed structures of (PhMe2Si)nCuLin - 1.LiX have been based solely on the stoichiometries of the precursors used in their generation. NMR studies dealing with the composition of these reagents have been recently reported: Singer, R. D.; Oehlschlager, A. C. JOC 1991, 56, 3510 and references therein.
18. Fleming, I.; Newton, T. W. JCS(P1) 1984, 1805.
19. Suzuki, M.; Koyano, H.; Noyori, R. JOC 1987, 52, 5583.
20. Ager, D. J.; Fleming, I. CC 1978, 177.
21. For Michael addition of (PhMe2Si)2CuLi to a,b-unsaturated sulfoxide, see Takaki, K.; Maeda, T.; Ishikawa, M. JOC 1989, 54, 58.
22. Fleming, I.; Goldhill, J. CC 1978, 176.
23. Related displacements of F, OTHP, and Cl with PhMe2SiLi have been described: (a) Hiyama, T.; Obayashi, M.; Sawahata, M. TL 1983, 24, 4113. (b) Ishii, T.; Kawamura, N.; Matsubara, S.; Utimoto, K.; Kozima, S.; Hitomi, T. JOC 1987, 52, 4416. (c) Fleming, I.; Sanderson, P. E. J.; Terret, N. K. S 1992, 69.
24. Magnus, P. D.; Sarkar, T.; Djuric, S. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, 1982; Vol. 7, pp 608-614.
25. Still, W. C. JOC 1976, 41, 3063.
26. (a) Baldwin, J. E.; Bottaro, J. C.; Riordan, P. D.; Derome, A. E. CC 1982, 942. For preparation of t-BuPh2SiLi, see: (b) Cuadrado, P.; Gonzalez, A. M.; Gonzales, B.; Pulido, F. J. SC, 1989, 19, 275.
27. (a) Wakamatsu, K.; Nonaka, T.; Okuda, Y.; Tückmantel, W.; Oshima, K.; Utimoto, K.; Nozaki, H. T 1986, 42, 4427. (b) Trost, B. M.; Tour, J. M. JOC 1989, 54, 484.
28. Fugami, K.; Hibino, J.; Nakatsukasa, S.; Matsubara, S.; Oshima, K.; Utimoto, K.; Nozaki, H. T 1988, 44, 4277 and references therein.
29. Okuda, Y.; Wakamatsu, K.; Tückmantel, W.; Oshima, K.; Nozaki, H. TL 1985, 26, 4629.

Anil S. Guram

Massachusetts Institute of Technology, Cambridge, MA, USA

Grant A. Krafft

Abbott Laboratories, Abbott Park, IL, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.