[69097-20-7]  · C11H28O3Si3  · Tris(trimethylsilyloxy)ethylene  · (MW 292.66)

(conversion of carboxylic acid chlorides to terminal a-hydroxy ketones;1,2 conversion of aldehydes and ketones to 2,3-dihydroxyalkanoic acids3,4)

Physical Data: bp 54-56 °C/0.1 mmHg; d 0.886 g cm-3.5

Solubility: sol all organic solvents; insol in H2O (reacts).

Form Supplied in: colorless free-flowing liquid; available commercially.

Preparative Methods: from the bis(trimethylsilyl) derivative of glycolic acid by either forming the enolate with Lithium Hexamethyldisilazide at -78 °C in THF and trapping with Chlorotrimethylsilane,1,2 or by the reaction with Trimethylsilyl Trifluoromethanesulfonate and Triethylamine at rt (eq 1).6

Handling, Storage, and Precautions: is readily hydrolyzed in protic solvents. It should be stored in a sealed container protected from the atmosphere. Since the reaction of the reagent with carboxylic acid chlorides and aldehydes under Lewis acid catalysis in the absence of solvent is highly exothermic, large-scale preparations may require regulation of the reaction temperature either by external cooling or by controlled addition of the reactants.

Carboxylic Acid Chlorides to Terminal a-Hydroxy Ketones.1,2

The reaction of 2 equiv of tris(trimethylsilyloxy)ethylene with octanoyl chloride in the absence of solvent either by heating to 90 °C for 2 h or by using a catalytic amount of Tin(IV) Chloride and allowing the reaction to freely exotherm results in the formation of (1), TMSCl, and bis(trimethylsilyl)-glycolic acid (eq 2). Treatment of the reaction mixture with dilute acid in THF or dioxane results in an immediate exothermic hydrolysis (presumably to b-keto acid 2) and decarboxylation to furnish the hydroxymethyl ketone (3). Since the rate of the reaction of the reagent with the liberated HCl (to furnish TMSCl, and bis(trimethylsilyl)glycolic acid) is as least as fast as with the acid chloride, 2 equiv of reagent must be used to achieve complete conversion to the hydroxymethyl ketone. Both aliphatic and aromatic acid chlorides have been used successfully. Very hindered acid chlorides (e.g. 1-adamantanecarbonyl chloride) failed to react. This methodology has been applied in the total synthesis of Ajugarin-IV7 and in the preparation of some prostaglandin analogs where the terminal hydroxymethyl ketone functional group serves as a biosteric replacement for a carboxylate group.8

Aldehydes and Ketones to 2,3-Dihydroxyalkanoic Acids.

The reaction of tris(trimethylsiloxy)ethylene with n-hexanal in the absence of solvent using SnCl4 as the catalyst is exothermic and furnishes the adduct (4). Direct hydrolysis of the reaction mixture with aqueous acetic acid in THF gives 2,3-dihydroxyoctanoic acid (5) as a mixture of diasteromers (eq 3).3 Similar reactions have also been accomplished under trimethylsilyl trifluoromethanesulfonate or Cesium Fluoride catalysis.4 Aliphatic, a,b-unsaturated, and aromatic aldehydes have been used successfully.3,4 Aliphatic and aromatic ketones have also been used successfully under trimethylsilyl trifluoromethanesulfonate catalysis conditions.4 This methodology usually results in poor stereoselectivity; both the erythro and threo isomers are obtained in comparable amounts.

Reaction with Ketenes.

The reaction of tris(trimethylsilyloxy)ethylene with ketene generated from acetyl chloride and triethylamine furnishes the adduct (6) in good yield (eq 4); this compound was an intermediate in the synthesis of a series of anthragallols.9 Similar products result from the reaction of the reagent with halogen-10,11 and trimethylsilyl-substituted ketenes.12

Electrophilic Addition of Acetals and Orthoesters.

With catalysis by trimethylsilyl trifluoromethanesulfonate, acetals and orthoesters undergo electrophilic addition to tris(trimethylsilyloxy)ethylene (eq 5).4

Electrophilic Addition of t-Alkyl and Benzyl Groups.

Compounds capable of forming a stabilized carbenium ion undergo Lewis acid-catalyzed addition to tris(trimethylsilyloxy)ethylene; these included t-alkyl halides13 and benzyl acetates14 (eq 6).

Related Reagents.

1,2-Diethoxy-1,2-bis(trimethylsilyloxy)ethylene; Ketene Bis(trimethylsilyl) Acetal; 1-Methoxy-1-(trimethylsilyloxy)propene; 1-Methoxy-2-trimethylsilyl-1-(trimethylsilyloxy)ethylene; Methylketene Bis(trimethylsilyl) Acetal; Methylketene Dimethyl Acetal; Tetramethoxyethylene.

1. Wissner, A. TL 1978, 31, 2749.
2. Wissner, A. JOC 1979, 44, 4617.
3. Wissner, A. S 1979, 1, 27.
4. Oesterle, T.; Simchen, G. LA 1987, 8, 693.
5. Catalog Handbook of Fine Chemicals, 1992-1993; Aldrich Chemical Company: Milwaukee; p 1266.
6. Oesterle, T.; Simchen, G. LA 1987, 8, 687.
7. Kende, A. S.; Roth, B.; Kubo, I. TL 1982, 23, 1751.
8. Wissner, A.; Birnbaum, J. E.; Wilson, D. E. JMC 1980, 23, 715.
9. Roberge, G.; Brassard, P. S 1981, 5, 381.
10. Brady, W. T.; Watts, R. D. JOC 1981, 46, 4047.
11. Saidi, K.; Habibi, M. H. JFC 1991, 51, 217.
12. Brady, W. T.; Saidi, K. JOC 1990, 55, 4215.
13. Reetz, M. T.; Heimbach, H. CB 1983, 116, 3702.
14. Reetz, M. T.; Walz, P.; Hübner, F.; Hüttenhain, S. H.; Heimbach, H.; Schwellnus, K. CB 1984, 117, 322.

Allan Wissner

Wyeth-Ayerst Research, Pearl River, NY, USA

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