[88738-21-0]  · C11H18OSSi  · Methoxy(phenylthio)trimethylsilylmethane  · (MW 226.45)

(convenient homologation reagent for carbonyl compounds and alkyl halides; acyl anion equivalent)

Physical Data: bp 120-122 °C/10 mmHg.

Solubility: sol ether, THF, dioxane, methanol, ethanol, benzene, hexane.

Form Supplied in: colorless liquid.

Preparative Method: from methoxy(phenylthio)methyllithium (see Methoxy(phenylthio)methane) with Chlorotrimethylsilane.1

Homologation of Carbonyl Compounds.

Methoxy(phenylthio)trimethylsilylmethyllithium (1), an acyl anion equivalent, is generated by treating methoxy(phenylthio)trimethylsilylmethane with n-Butyllithium at -80 °C in THF. This anion adds to carbonyl compounds in 1,2-fashion, providing ketene O,S-acetals via Peterson alkenation (eq 1).1a The ketene O,S-acetals thus obtained are converted to methyl esters by methanolysis in the presence of Hydrogen Chloride and Mercury(II) Chloride. This procedure was applied to the synthesis of (±)-b-eudesmol (eq 2).1a

Cleavage of the ketene O,S-acetals under neutral or mildly basic conditions can be executed by using Iodotrimethylsilane to give the phenyl thioester or the ketene O-silyl,S-acetal (eqs 3 and 4).2 In addition, amides can be prepared by sequential treatment of ketene O,S-acetals with lithium thiomethoxide in HMPA followed by addition of an amine (eq 5).2

The reaction of anion (1) with cyclic a,b-unsaturated ketones provides 1,4-addition products in the presence of HMPA (eqs 6 and 7).3 The resulting enolate can be trapped with various alkyl halides to give a- and b-disubstituted cyclic ketones with the trans configuration. This protocol was successfully applied to syntheses of sarkomycin and prostaglandin.4

Homologation of Alkyl Halides.

Carbanion (1) serves as an acylsilane anion equivalent in reactions with alkyl halides. The alkylation proceeds smoothly at -40 °C in the presence of HMPA to provide O,S-acetals which are easily transformed into acylsilanes via oxidation with Sodium Periodate in wet dioxane (eq 8).5 Acetalization of acylsilanes gives a-trimethylsilyl acetals, which are orthoester synthetic equivalents (eq 9).6 The synthesis of isocarbacyclin was achieved by using this procedure.

In another synthetic application, the alkylation products of (1) undergo facile thermal elimination of methanol to afford (Z)-1-phenylthio-1-trimethylsilylalkenes in good yields with high stereoselectivity (eq 10).7 The elimination is facilitated by oxygen and is further accelerated by the addition of Triethylborane, which implies the involvement of a radical pathway. The resulting (Z)-1-phenylthio-1-trimethylsilylalkenes are transformed into (E)-vinylsilanes by reductive cleavage of the thiophenyl group with Lithium Naphthalenide (eq 11).7

Homologation of Arenes and Alk-1-enes.

Methoxy(phenylthio)trimethylsilylmethane undergoes Friedel-Crafts reaction with arenes in the presence of Lewis acids such as Titanium(IV) Chloride and Tin(IV) Chloride to afford (aryl(phenylthio)methyl)trimethylsilanes (eq 12).8 This reagent also reacts with terminal alkenes in the presence of SnCl4 to give ene products (eq 13).8

1. (a) Groot, A. D.; Jansen, B. J. M. SC 1983, 13, 985. (b) Rawal, V. H.; Akiba, M.; Cava, M. P. SC 1984, 14, 1129.
2. Hackett, S.; Livinghouse, T. TL 1984, 25, 3539.
3. (a) Otera, J.; Niibo, Y.; Aikawa, H. TL 1987, 28, 2147. (b) Otera, J.; Niibo, Y.; Nozaki, H. JOC 1989, 54, 5003.
4. Otera, J.; Niibo, Y.; Nozaki, H. TL 1992, 33, 3655.
5. Mandai, T.; Yamaguchi, M.; Nakayama, Y.; Otera, J.; Kawada, M. TL 1985, 26, 2675.
6. Mandai, T.; Matsumoto, S.; Kohama, M.; Kawada, M.; Tsuji, J.; Saito, S.; Moriwake, T. JOC 1990, 55, 5671.
7. Mandai, T.; Kohama, M.; Sato, H.; Kawada, M.; Tsuji, J. T 1990, 46, 4553.
8. Han, D. I.; Oh, D. Y. SC 1989, 19, 2213.

Tadakatsu Mandai

Okayama University of Science, Japan

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