[10026-04-7]  · Cl4S2  · Tetrachlorosilane  · (MW 169.89)

(precursor of chlorotrialkylsilanes; Lewis acid catalyst)

Physical Data: mp -70 °C; bp 57.6 °C; d 1.483 g cm-3.

Solubility: sol benzene, ether, chloroform, petroleum ether, dichloromethane.

Form Supplied in: neat as clear colorless liquid; as 1.0 M solution in dichloromethane.

Handling, Storage, and Precautions: the neat liquid and solutions react violently with water and protic solvents to produce HCl gas. The neat reagent reacts violently and/or explosively with DMSO and DMF. Avoid contact with metals, strong bases, strong acids, and glass. Corrosive; stench; handle and store under N2; store cool. Use in a fume hood.

Chlorosilane Precursor.

Tetrachlorosilane serves as a useful precursor to tri-, di-, and monosilyl chlorides.1 Substitution by metal alkoxides and phenoxides,2 as well as alkyl, vinyl,3 and aryl organometal nucleophiles, have been reported (eqs 1 and 2). An extremely hindered chlorosilane has been prepared from tri-t-butylphenoxide and tetrachlorosilane.4

Treatment of tetrachlorosilane with 4 equiv of a propargyl Grignard reagent afforded, after zirconocene-promoted cyclization and sulfurization, a spiro-fused tetracyclic compound which serves as a precursor to orthogonally fused conducting polymers (eq 3).5

Coupling Reagent for Amide Formation.

Tetrachlorosilane in pyridine has been shown to facilitate amide formation from carboxylic acids and alkyl and aryl amines (eq 4).6

Acetal and Thioacetal Formation.

Tetrachlorosilane has been shown to convert a,b-unsaturated ketones, in the presence of ethylene glycol, to b-chloro acetals (eq 5).7 Similarly, a propargyl ketone was transformed into the corresponding b,b-dichloro acetal under the same conditions (eq 6).

Dithioacetals of aryl aldehydes are efficiently formed upon treatment with 2 equiv of thiol in the presence of tetrachlorosilane (eq 7).8 Aryl ketones (e.g. acetophenone or benzophenone) were not converted under the reaction conditions, while treatment of aliphatic ketones with tetrachlorosilane and dimercaptoethane resulted in some vinyl sulfide byproduct, as well as the desired dithioacetal (eq 8).

Cyclization Promoter.

Tetrachlorosilane was the Lewis acid promoter of choice for a critical cyclization step towards the synthesis of the alkaloids julandine and ipalbidine (eq 9).9 Other Lewis acids evaluated were TiCl4, SnCl4, BF3.Et2O, ZrCl4, AlCl3, and FeCl3. Tetrachlorosilane, and several other Lewis acids, were evaluated as promoters for Fischer indole synthesis reactions.10

Disulfide Bond Formation.

In conjunction with diphenyl sulfoxide, tetrachlorosilane in trifluoroacetic acid (TFA) has been shown to effectively facilitate disulfide bond formation in the synthesis of cystine-containing peptides.11,12 As shown in eq 10, the tetrachlorosilane-diphenyl sulfoxide-TFA system serves to activate the protected SH moiety of cysteine residue side-chains in peptides to afford, after nucleophilic attack of a second protected cysteine thiol, a disulfide bridge. A number of S-protecting groups were employed in the study, including acetamidomethyl (Acm), trimethylacetamidomethyl (Tacm), benzamidomethyl (Bam), t-butyl, isopropyl, 4-methoxybenzyl, 4-methylbenzyl, and 4-nitrobenzyl. Similarly, methyltrichlorosilane can be used in place of tetrachlorosilane to effect this transformation and, due to its ease of handling relative to tetrachlorosilane, is recommended by the authors.

The chlorosilane-diphenyl sulfoxide oxidation system is operationally superior to both air and iodine, which are also used to facilitate peptide disulfide bond formation, due to shorter reaction times and improved regio- and chemoselectivity.

Friedel-Crafts Acylation Catalyst.

Tetrachlorosilane-Silver(I) Perchlorate has been employed as a catalyst to effect the Friedel-Crafts acylation of anisole by hexanoic acid anhydride (eq 11).13 Other Lewis acids used in combination with AgClO4 which were evaluated in the study and shown to be as effective or better than SiCl4 were GaCl4, GeCl4, SnCl4, BCl3, and AlCl3. Lewis acids which were not as effective as SiCl4 for this application were InCl3, SbCl5, TiCl4, ZrCl4, and HfCl4.

1. (a) Silicon Chemistry; Corey, J. Y.; Corey, E. R.; Gaspar, P. P., Eds.; Horwood: Chichester, 1987. (b) Organosilicon Compounds; Eaborn, C., Ed.; Butterworths: London, 1960.
2. Leis, C.; Wilkinson, D. L.; Handwerker, H.; Zybill, C.; Müller, G. OM 1992, 11, 514.
3. Ziche, W.; Auner, N.; Behm, J. OM 1992, 11, 2494.
4. Schafer, A.; Weidenbruch, M.; Pohl, S.; Saak, W. ZN(B) 1990, 45b, 1363.
5. Tour, J. M.; Wu, R.; Schumm, J. S. JACS 1990, 112, 5662.
6. Chan, T. H.; Wong, L. T. L. JOC 1969, 34, 2766.
7. Gil, G. TL 1984, 3805.
8. Oh, D. Y.; Ku, B. SC 1989, 433.
9. Cragg, J. E.; Hedges, S. H.; Herbert, R. B. TL 1981, 2127.
10. Prochazka, M. P.; Carlson, R. ACS 1989, 43, 651.
11. Akaji, K.; Tatsumi, T.; Yosida, M.; Kimura, T.; Fujiwara, Y.; Kiso, Y. JACS 1992, 114, 4137.
12. Akaji, K.; Tatsumi, T.; Yosida, M.; Kimura, T.; Fujiwara, Y.; Kiso, Y. CC 1991, 167.
13. Harada, T.; Ohno, T.; Kobayashi, S.; Mukaiyama, T. S 1991, 1216.

David P. Sebesta

University of Colorado, Boulder, CO, USA

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