Lithium Bis[dimethyl(phenyl)silyl]cuprate1

(PhMe2Si)2CuLi

[75583-57-2]  · C16H22CuLiSi2  · Lithium Bis[dimethyl(phenyl)silyl]cuprate  · (MW 341.01)

(dimethyl(phenyl)silyl nucleophile for making Si-C bonds by reaction with a,b-unsaturated carbonyl compounds, alkynes, allenes, and allylic acetates)

Physical Data: typically a 0.6M, dark, reddish-brown solution in THF.

Analysis of Reagent Purity: the silyllithium solution can be double-titrated for active reagent using Allyl Bromide, but the cuprate is usually used without further checks; NMR (of the cuprate made with CuCN in THF-d8): 1H d 0.09; 13C d 5.1; 29Si d -24.4; 7Li d -3.33.2

Preparative Methods: the silyl cuprate is prepared1 from the corresponding silyllithium reagent (Dimethylphenylsilyllithium); commercially available Chlorodimethylphenylsilane is stirred with Lithium shot, wire, or powder under Ar or N2 in THF at 0 °C for 4-12 h; the silyllithium solution may also be prepared, free of halide ion, by cleaving tetramethyldiphenyldisilane with lithium and ultrasound irradiation;2 the silyllithium solution (2 equiv), after assay, is transferred by syringe on to anhyd Copper(I) Iodide, Copper(I) Bromide, or Copper(I) Cyanide (1 equiv), kept under argon or nitrogen at 0 °C, stirred at this temperature for 20 min, and then used immediately.

Handling, Storage, and Precautions: must be kept free of O2 and H2O; while somewhat more stable thermally than alkyl cuprates, surviving for a few hours at 0 °C, it is best used immediately after its preparation; the copper salts, and especially copper(I) cyanide, are toxic; the solutions should therefore be handled in a fume hood wearing impermeable gloves, and the aqueous washings disposed of appropriately, immediately after use.

Introduction.

Because dimethyl(phenyl)silyllithium is much easier to prepare than Trimethylsilyllithium, the most commonly used silyl cuprate reagent is derived from this silyl group. The reagent can be prepared using CuI, CuBr.SMe2, or CuCN. The three reagents appear to be very similar in their reactivity, except for the higher regioselectivity of the cyanide-derived reagent with terminal alkynes. The dimethyl(phenyl)silyl group in products like allyl- and vinylsilanes appears to impart very similar reactivity to that imparted by the trimethylsilyl group, and it has an advantage over the trimethylsilyl group in that the presence of the phenyl group allows the dimethyl(phenyl)silyl group to be converted into a hydroxyl group with retention of configuration at carbon (eq 1). This transformation requires first a reaction with an electrophile, such as a proton,3 bromine, or the mercury(II) cation,4 to remove the phenyl ring and place a nucleofugal group X on the silicon atom. This step is followed by treatment either with peracid or with Hydrogen Peroxide and a base. The two steps may be combined in one pot;4 bromine itself does not have to be used, since the Peracetic Acid oxidizes bromide ion to bromine in situ.

This capacity of the dimethyl(phenyl)silyl group cannot be drawn upon, however, when there is a C=C double bond in the molecule; no matter which electrophile is used, it attacks the double bond more rapidly than it removes the phenyl ring from the silyl group. This limitation has been overcome using the corresponding diethylamino(diphenyl)silyl-5 and 2-methylbut-2-enyl(diphenyl)silylcuprate6 reagents.

A mixed cuprate, [dimethyl(phenyl)silyl]methyl(or-butyl)cuprate,7 containing one silyl and one alkyl group, has some advantages. Only the silyl group is transferred to the substrate, and hence only one silyl group is needed, and the byproduct of the silyl-cupration step, methane or butane, is volatile. Yields in silyl-cupration reactions carried out with only 1:1 stoichiometry are apt not to be quite so good, however. Other silyl copper reagents and cuprates with more specific or limited applications are (t-butyldimethylsilyl)butylcuprate,8 triphenylsilylcopper,9 the bis(t-butyldiphenylsilyl)cuprate,10 and the bis[tris(trimethylsilyl)silyl]cuprate.11

Reaction with a,b-Unsaturated Carbonyl Compounds.

Although silyllithium reagents add kinetically at the b-position of a,b-unsaturated ketones,12 the reactions are better with the cuprate when the enone is hindered.13 The cuprate, unlike the lithium reagent, also reacts with a,b-unsaturated aldehydes, esters (eq 2), amides, and nitriles13 and with vinyl sulfoxides.14 With esters, the intermediate enolates, which have the (E) geometry (1), may be used directly in highly stereoselective reactions with alkyl halides and aldehydes.15,16 The b-hydroxy esters, such as (2), can be used in the synthesis of allylsilanes.17

a,b-Unsaturated carbonyl compounds attached to a homochiral auxiliary, such as Koga's lactam or Oppolzer's sultam, give products with a stereogenic center carrying a silyl group having high levels of enantiomeric purity.18,19

Reaction with Alkynes.

The silyl cuprate reacts with alkynes by syn stereospecific metallo-metallation (eq 3). Provided that the cuprate is derived from copper cyanide, the regioselectivity with terminal alkynes is highly in favor of the isomer with the silyl group on the terminus. The intermediate vinyl cuprate (3) reacts with many substrates, familiar in carbon-based cuprate chemistry, to give overall syn addition of a silyl group and an electrophile to the alkyne.20 A curious feature of this reaction is that the intermediate (3), although uncharacterized, has the stoichiometry of a mixed silicon-carbon cuprate, and yet it transfers the carbon-based group to most substrates, in contrast to the behavior of mixed silyl alkyl cuprates.

Disubstituted alkynes also react, and, if the two substituents are well differentiated sterically, as with a methyl group on one side and a branched chain on the other, the regioselectivity is highly in favor of the silyl group appearing at the less hindered end.

Reaction with Allenes.

Allenes react with the silyl cuprate at low temperature. The regiochemistry with allene itself places the silyl group on the central carbon atom and the added electrophile at the terminus (eq 4).21 One surprising exception to this rule is with iodine as the electrophile, when the product (5) has the opposite regiochemistry even from that of the reaction with chlorine. Since the iodide (5) can be converted into a lithium reagent [and a cuprate that is not identical with (4)], it is possible to achieve overall either regiochemistry in additions to allene. Monosubstituted allenes give mixtures of regioisomers,21,22 and disubstituted and trisubstituted allenes give largely allylsilanes whatever electrophile is used. The metallo-metallation step is stereospecifically syn.23

Reaction with Allylic Acetates.

Silyl cuprates react with allylic acetates to give allylsilanes directly (eqs 5-7). Allylic acetates that are secondary at both ends are apt to give both regioisomers. Some control of the regiochemistry is possible, however, by using a cis double bond; this encourages reaction with allylic shift, especially when the silyl group is delivered to the less-hindered end of the allylic system (eq 5).24 An alternative protocol, assembling a mixed silyl cuprate on a carbamate group, is even better in controlling the regioselectivity, usually giving complete allylic shift (eq 6).24,25 Tertiary acetates, on the other hand, are very well behaved regiochemically, giving only the product with the silyl group at the less-substituted end of the allylic system (eq 7).25,26 Allylsilanes have many uses as carbon nucleophiles in organic synthesis.27

The acetate reaction (eq 5) and the carbamate alternative (eq 6) are complementary in their stereochemistry, the former taking place stereospecifically anti and the latter stereospecifically syn.24,25

Other Reactions.

Other substrates that have been found to react with silyl-copper reagents and with silyl cuprates are allyl chlorides,28 an alkyl bromide,29 epoxides,8,22 acid chlorides,9,30 propargyl acetates31 and sulfides,32 a vinyl iodide,9 an aminomethyl acetate,33 ethyl tetrolate,34 and some strained allylic ethers.35


1. Fleming, I. In Organocopper Reagents; R. J. K. Taylor, Ed.; OUP: Oxford, 1995; p. 257.
2. Sharma, S.; Oehlschlager, A. C. T 1989, 45, 557; JOC 1991, 56, 770.
3. Fleming, I.; Henning, R.; Plaut, H. CC 1984, 29.
4. Fleming, I.; Sanderson, P. E. J. TL 1987, 28, 4229.
5. Tamao, K.; Kawachi, A.; Ito, Y. JACS 1992, 114, 3989.
6. Fleming, I.; Winter, S. B. D. TL 1993, 34, 7287.
7. Fleming, I.; Newton, T. W. JCS(P1) 1984, 1805.
8. Lipshutz, B. H.; Reuter, D. C.; Ellsworth, E. L. JOC 1989, 54, 4975.
9. Duffaut, N.; Dunoguès, J.; Biran, C.; Calas, R.; Gerval, J. JOM 1978, 161, C23.
10. Cuadrado, P.; Gonzalez, A. M.; Gonzalez, B.; Pulido, F. J. SC 1989, 19, 275.
11. Chen, H.-M.; Oliver, J. P. JOM 1986, 316, 255.
12. (a) Still, W. C. JOC 1976, 41, 3063. (b) Still, W. C.; Mitra, A. TL 1978, 2659.
13. Ager, D. J.; Fleming, I.; Patel, S. K. JCS(P1) 1981, 2520.
14. Takaki, K.; Maeda, T.; Ishikawa, M. JOC 1989, 54, 58.
15. Crump, R. A.; Fleming, I.; Hill, J. H. M.; Parker, D.; Reddy, N. L.; Waterson, D. JCS(P1) 1992, 3277.
16. Fleming, I.; Kilburn, J. D. JCS(P1) 1992, 3295.
17. Fleming I.; Gil, S.; Sarkar, A. K.; Schmidlin, T. JCS(P1) 1992, 3351.
18. Fleming, I.; Kindon, N. D. CC 1987, 1177.
19. Oppolzer, W.; Mills, R. J.; Pachinger, W.; Stevenson, T. HCA 1986, 69, 1542.
20. Fleming, I.; Newton, T. W.; Roessler, F. JCS(P1) 1981, 2527.
21. (a) Fleming, I.; Rowley, M.; Cuadrado, P.; González-Nogal, A. M.; Pulido, F. J. T 1989, 45, 413. (b) Morizawa, Y.; Oda, H.; Oshima, K.; Nozaki, H. TL 1984, 25, 1163.
22. Singh, S. M.; Oehlschlager, A. C. CJC 1991, 69, 1872.
23. Fleming, I.; Landais, Y.; Raithby, P. R. JCS(P1) 1991, 715.
24. Fleming, I.; Higgins, D.; Lawrence, N. J.; Thomas, A. P. JCS(P1) 1992, 3331.
25. Fleming, I.; Terrett, N. K. JOM 1984, 264, 99.
26. Fleming, I.; Marchi, D. S 1981, 560.
27. Fleming, I.; Dunoguès, J.; Smithers, R. OR 1989, 37, 575.
28. Smith, J. G.; Drozda, S. E.; Petraglia, S. P.; Quinn, N. R.; Rice, E. M.; Taylor, B. S.; Viswanathan, M. JOC 1984, 49, 4112.
29. (a) Singer, R. D.; Oehlschlager, A. C. JOC 1991, 56, 3510. (b) Fürstner, A.; Weidmann, H. JOM 1988, 354, 15.
30. Brook, A. G.; Harris, J. W.; Lennon, J.; Sheikh, M. E. JACS 1979, 101, 83.
31. Fleming, I.; Takaki, K.; Thomas, A. JCS(P1) 1987, 2269.
32. Casarini, A.; Jousseaume, B.; Lazzari, D.; Porciatti, E.; Reginato, G.; Ricci, A.; Seconi, G. SL 1992, 981.
33. Nativi, C.; Ricci, A.; Taddei, M. TL 1990, 31, 2637.
34. Audia, J. E.; Marshall, J. A. SC 1983, 13, 531.
35. (a) Lautens, M.; Belter, R. K.; Lough, A. J. JOC 1992, 57, 422. (b) Lautens, M.; Ma, S.; Belter, R. K.; Chiu, P.; Leschziner, A. JOC 1992, 57, 4065.

Ian Fleming

Cambridge University, UK



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