Trimethylsilylketene1

[4071-85-6]  · C5H10OSi  · Trimethylsilylketene  · (MW 114.24)

(reactive acylating agent for amines and alcohols;2 building block for synthesis of coumarins;3 synthesis of a-silyl ketones via the addition of organocerium reagents;4 treatment with stabilized ylides forms trimethylsilyl-substituted allenes;2a cycloaddition with aldehydes affords b-lactones;5 forms small rings with diazomethane;6 treatment with n-BuLi forms a ketene enolate7)

Physical Data: 2a,7 bp 81-82 °C; d 0.80 g cm-3.

Solubility: sol CH2Cl2, CHCl3, CCl4, THF, diethyl ether, and most standard organic solvents; reacts with alcoholic and amine solvents.

Form Supplied in: colorless oil; not commercially available.

Analysis of Reagent Purity: 8 IR (CCl4) 2130 cm-1; 1H NMR (60 MHz, CCl4) d 1.65 (s, 1 H), 0.12 (s, 9 H) ppm; 13C NMR (50.3 MHz, CDCl3) d 179.4, 0.5, -0.2 ppm.

Preparative Methods: most often prepared (eq 1) by pyrolysis of Ethoxy(trimethylsilyl)acetylene at 120 °C (100 mmol scale, 65% yield).2a Recently, pyrolysis of t-butoxy(trimethylsilyl)acetylene has been shown to be a convenient alternative for the preparation of trimethylsilylketene (1). Thermal decomposition of t-butoxy(trimethylsilyl)acetylene causes elimination of 2-methylpropene slowly at temperatures as low as 50 °C and instantaneously at 100-110 °C (30 mmol scale, 63% yield).8 The main advantage of this method is that it is possible to generate trimethylsilylketene in the presence of nucleophiles, leading to in situ trimethylsilylacetylation (eq 2). Increased shielding of the triple bond prevents problems such as polymerization and nucleophilic attack that occur when the ketene is generated in situ from (trimethylsilyl)ethoxyacetylene. Trimethylsilylketene can also be prepared (eq 3) via the dehydration of commercially available Trimethylsilylacetic Acid with 1,3-Dicyclohexylcarbodiimide (DCC) in the presence of a catalytic amount of Triethylamine (100 mmol scale, 63%).9 Other typical methods used for ketene generation such as dehydrohalogenation of the acyl chloride10 and pyrolysis of the anhydride10b,11 have been applied to the preparation of (1); however, both methods afford low yields.

Purification: purified by distillation at 82 °C/760 mmHg.

Handling, Storage, and Precautions: unusually stable for an aldoketene with respect to dimerization and decomposition. Samples stored neat under nitrogen at room temperature show no noticeable decomposition after several months.

Trimethylsilylacetylation of Alcohols and Amines.

Trimethylsilylketene (1) has been used as a potent acylating agent for amines and alcohols (eq 4).2a It reacts almost instantaneously with hindered amines to form a-silyl amides in quantitative yield. Reaction with alcohols such as t-butanol is much slower (CCl4, 48 h, rt, 80% yield). However, Boron Trifluoride Etherate strongly catalyzes a-silylacetate formation. Hindered tertiary alcohols that cannot be acylated by standard reagents such as benzoyl chloride, acetyl chloride, and acetic anhydride (even in the presence of DMAP) can be acylated by (1). Desilylation can be effected using Potassium Fluoride in methanol to produce the acetate directly (eq 5).12 When the addition of alcohols to (1) is catalyzed by zinc halides, a high degree of functionality can be tolerated in the substrate, including carbonyl, acetal, thioacetyl, epoxy, and alkenic groups.2b In contrast, BF3.Et2O catalysis results in partial product desilylation with alcohols containing carbonyl groups and also causes cleavage of acetal groups. Other reactions used to prepare a-silyl acetates including the Reformatsky reaction,13 C-silylation of esters,14 and silyl migration from acylsilanes15 are incompatible with many active functional groups. Functionalized a-silyl acetates serve as useful precursors to butenolides (eq 6).2b

Synthesis of Coumarins via Cyclization-Elimination.

Reaction of (1) with o-acylphenols affords coumarins in high yields in a one-pot reaction (eq 7).3 The reaction is applicable to a variety of functionalized aromatic systems. Coumarins form more readily in somewhat higher yield using this procedure as compared to a similar method involving the use of a cumulated phosphorus ylide reagent, Ketenylidenetriphenylphosphorane.16 Workup and product isolation is easier in view of the triphenylphosphine oxide byproduct formed in the ylide reaction. Other methods used to convert o-acylphenols to coumarins include approaches based on Knovenagel17 and Pechmann18 reactions. The method described above involves milder conditions and often provides coumarins in higher yields.

One-pot Formation of a-Silyl Ketones.

a-Silyl ketones can be prepared in a one-pot synthesis by the addition of organocerium reagents to (1) followed by subsequent quenching with aqueous ammonium chloride or alkyl halides (eq 8).4 The organocerium reagents can be easily prepared from Cerium(III) Chloride and an alkyl- or aryllithium. Organolithium reagents are not suitable for this reaction because proton abstraction is preferred resulting only in complicated reaction mixtures of products.7 A variety of other methods have been reported for the synthesis of a-silyl ketones, including methods based on 1,3-O to C silyl migration from lithiated silyl enol ethers,19 other types of migration from silicon-containing compounds,20 isomerization of silicon-containing allyl alcohols,21 and Si-H insertion reactions of diazo ketones,22 as well as classical preparations involving carboxylic acid derivatives23 and the oxidation of b-hydroxy silanes.21,23 However, most of these methods require multistep procedures and are less convenient.

Preparation of Trimethylsilyl-Substituted Allenes.

Treatment of (1) with a stabilized phosphorus ylide, (Ethoxycarbonylmethylene)triphenylphosphorane, affords the silyl substituted allenic ester in 85% yield (eq 9).2a These alkenation reactions only occur with stabilized phosphorus ylides; unstabilized ylides reportedly form complex mixtures with trimethylsilylketene.

Preparation of b-Lactones.

Reaction of (1) with saturated aldehydes in the presence of BF3.Et2O results in mixtures of both cis- and trans-2-oxetanones (eq 10). Ketones are reported not to undergo cycloadditions with (1).5c,d Cycloadditions have been described with both saturated and a,b-unsaturated aldehydes. Distillation is reported to promote a 1,3-shift of the organosilyl group accompanied by ring opening to yield the trimethylsilyl dienoate ester.5a

Recently, a method for the stereoselective preparation of the cis-substituted b-lactones using catalytic Methylaluminum Bis(4-bromo-2,6-di-t-butylphenoxide) has been described (eq 11).5e This method is reported to work well for alkyl, aryl, and unsaturated aldehydes. Stoichiometric amounts of catalyst lead to desilylation followed by ring opening to afford (Z)-alkenoic acids.

Reaction with Diazomethane to Form Silylated Cyclopropanes and Cyclobutanones.

The reaction of (1) and Diazomethane results in a mixture of products. Treatment of equimolar amounts of (1) with diazomethane at -130 °C leads to (trimethylsilyl)cyclopropanone in moderate yield (eq 12).6 The product obtained can then react with a second equivalent of diazomethane upon warming to -78 °C, resulting in ring expansion to a mixture of 2- and 3-(trimethylsilyl)cyclobutanones. Alternatively, these isomeric products may be obtained directly with 2 equiv of diazomethane. Treatment of the isomeric (trimethylsilyl)cyclobutanone mixture with methanol makes it possible to obtain pure 3-substituted isomer in 84% yield.24 This 3-(trimethylsilyl)cyclobutanone derivative can also be formed by a more elaborate route via the regioselective [2 + 2] addition of Dichloroketene to Trimethylsilylacetylene followed by hydrogenation and reductive removal of the two chlorine atoms.25 Trimethylsilyldiazomethane has also been reported to react with (1) to form bis-silyl substituted cyclopropanones.26

Formation of the Ketene Enolate.

Addition of (1) to a solution of n-Butyllithium at -100 °C presumably forms the ketene enolate. Quenching with Chlorotrimethylsilane then affords the bis-silylketene in high yield (eq 13).7 Attempts to trap the enolate with other electrophiles have been unsuccessful. Other methods27 affording bis(trimethylsilyl)ketene have been reported including a very similar method involving deprotonation of (1) with Triethylamine and quenching with Trimethylsilyl Trifluoromethanesulfonate.28 However, the yield for this reaction is much lower (48%). Other reactions report bis(trimethylsilyl)ketene as a byproduct.29


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Jennifer L. Loebach & Rick L. Danheiser

Massachusetts Institute of Technology, Cambridge, MA, USA



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