[4206-67-1]  · C4H11ISi  · (Iodomethyl)trimethylsilane  · (MW 214.14)

(electrophile for the preparation of allylsilanes2 and propargylsilanes;3 forms carbon alkylation adducts useful for alkene synthesis;4 alkylation adducts are frequently a source of fluoride-induced reactive intermediates, forming nitrogen5 and sulfur6 alkylation adducts that function as ylide precursors; readily undergoes metal-halogen exchange to generate a reagent for Peterson methylenation7)

Alternate Name: trimethylsilylmethyl iodide.

Physical Data: bp 140-142 °C; d 1.442 g cm-3.

Form Supplied in: colorless liquid; widely available.

Handling, Storage, and Precautions: highly flammable liquid; corrosive; irritant; should be stored cold, protected from light, and stabilized with copper metal. Handle in a fume hood.

Allylsilane and Propargylsilane Synthesis.

(Iodomethyl)trimethylsilane has been used to prepare allylsilanes, which are typically utilized in Lewis acid or fluoride ion-promoted reactions with carbonyl compounds to provide homoallylic alcohols. Treatment of Me3SiCH2I with Methyltriphenylphosphonium Bromide and base produces an intermediate phosphonium salt which can be further utilized to prepare allylsilanes from carbonyl compounds.2a,b This procedure has been modified so that this series of transformations can be done as a one-pot procedure (eq 1).2c

More recently, it has been demonstrated that activated vinylcuprates can be directly added to Me3SiCH2I to give functionalized allylsilanes in moderate yields (eqs 2-4).8

The synthesis of propargylsilanes has also been thoroughly explored, and these useful reagents are readily prepared by the addition of substituted lithioacetylides to Me3SiCH2I.3 Propargylsilanes have subsequently been used in Titanium(IV) Chloride-promoted reactions with acetals to yield functionalized a-allenylsilanes or functionalized alkenes.

Alkene Synthesis.

a-Alkylation of ketones with Me3SiCH2I, followed by a bromination/elimination sequence, gives rise to a-methylene ketones (eq 5).4a

a-Alkylation of sulfones with Me3SiCH2I, followed by fluoride-induced elimination of the resultant b-silyl sulfones, cleanly produces alkenes, and this method has been applied to the synthesis of terminal alkenes, 1,4-dienes (by sequential dialkylation with Allyl Bromide and Me3SiCH2I), 1,3-dienes (eq 6), and exo-methylene compounds (eq 7).4b The intermediate b-silyl sulfones function as a synthon for CH2=CH-.

Generation of Nitrogen and Sulfur Ylides.

N-Trimethylsilylmethyl amides, prepared by the alkylation of the deprotonated amide with Me3SiCH2I, provide convenient access to nonstabilized azomethine ylide precursors. This method involving fluoride-promoted generation of a nonstabilized imidate ylide for 1,3-dipolar cycloaddition has been applied to the efficient construction of a key intermediate for the synthesis of the pyrrolizidine alkaloids retronecine and indicine by in situ trapping of the ylide intermediate with Methyl Acrylate (eq 8).5 This more versatile desilylation method of ylide generation and trapping with dipolarophiles demonstrates applicability to a wider range of synthetic targets than those derived from a-deprotonation of iminium salts, where an often unwanted anion-stabilizing substituent is required.

Similarly, the Cesium Fluoride-induced desilylation of a-trimethylsilylbenzylsulfonium alkyl triflate salts produces sulfur ylides, which rapidly equilibrate in DME solution to the thermodynamically more stable ylide prior to reaction with aromatic aldehydes to produce predominantly trans-diaryl epoxides in high yields.6a In the absence of an aldehyde trapping agent, Sommelet-Hauser rearrangements occur.

Related Reagents.

(Chloromethyl)trimethylsilane; Trimethylsilylmethyllithium; Trimethylsilylmethylmagnesium Chloride; Trimethylsilyl Trifluoromethanesulfonate.

1. There are currently no published reviews on the use of this reagent. For a review of (chloromethyl)trimethylsilane, see Anderson, R. S 1985, 717.
2. (a) Seyferth, D.; Wursthorn, K. R.; Mammarella, R. E. JOC 1977, 42, 3104. (b) Seyferth, D.; Wursthorn, K. R.; Lim, T. F. O.; Sepelak, D. J. JOM 1979, 181, 293. (c) Fleming, I.; Paterson, I. S 1979, 446. (d) Iio, H.; Ishii, M.; Tsukamoto, M.; Tokoroyama, T. TL 1988, 29, 5965. (e) Chakraborty, R.; Simpkins, N. S. T 1991, 47, 7689.
3. (a) Pornet, J.; Kolani, N. TL 1981, 22, 3609. (b) Pornet, J.; Randrianoelina, B.; Miginiac, L. TL 1984, 25, 651. (c) Pornet, J.; Damour, D.; Miginiac, L. T 1986, 42, 2017. (d) Pornet, J. JOM 1988, 340, 273.
4. (a) Fleming, I.; Goldhill, J. JCS(P1) 1980, 1493. (b) Kocienski, P. J. TL 1979, 20, 2649.
5. Vedejs, E.; Larsen, S.; West, F. G. JOC 1985, 50, 2170.
6. (a) Padwa, A.; Gasdaska, J. R. T 1988, 44, 4147. (b) Vedejs, E.; Martinez, G. R. JACS 1979, 101, 6452.
7. (a) Ager, D. S 1984, 384. (b) Chan, T. H.; Chang, E. JOC 1974, 39, 3264. (c) Peterson, D. J. JOC 1968, 33, 780.
8. Majetich, G.; Leigh, A. J. TL 1991, 32, 609.

Todd K. Jones & Lawrence G. Hamann

Ligand Pharmaceuticals, San Diego, CA, USA

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