Trimethylsilylmethyllithium1

[1822-00-0]  · C4H11LiSi  · Trimethylsilylmethyllithium  · (MW 94.18)

(methylenation of carbonyl compounds;1b reacts with carboxylic acid derivatives to provide a-silyl ketones;1d,2 synthesis of allylsilanes1k,3)

Physical Data: mp 112 °C.

Solubility: sol ethereal solvents; reacts with protic solvents.

Preparative Methods: obtained by reaction of (Chloromethyl)trimethylsilane with Lithium metal in an inert solvent.4 It is also available by displacement of a heteroatom group based on sulfur,5 silicon,6 or tin.7

Handling, Storage, and Precautions: reacts with protic solvents. It should be prepared and handled in inert solvents under an atmosphere of dry nitrogen or argon.

Peterson Alkenation.

Trimethylsilylmethyllithium (1) provides an alternative to a Wittig approach for the preparation of methylene compounds from carbonyl precursors.1b,c,7 In some cases the use of (1) is superior to the Wittig approach.8 Condensation of (1) with a carbonyl compound results in the formation of a b-hydroxysilane. Elimination to the alkene can be accomplished by use of acidic or basic conditions (eq 1).1a,b,9 Acetyl Chloride or Thionyl Chloride can also be used to accomplish this elimination.10 A wide variety of aldehydes and ketones have been used as substrates in this reaction.1b The use of Cerium(III) Chloride has been advocated with reagent (1) to favor nucleophilic addition with enolizable carbonyl compounds. The use of the lithium agent (1) gives superior yields compared to the use of Trimethylsilylmethylmagnesium Chloride with cerium.11

The carbonyl compound can also contain additional functionality.1b,12 Thus, treatment of an a,b-epoxy ketone with excess lithium reagent (1) provides the allyl alcohol (2) (eq 2).13 The use of an a-phenyl selenoaldehyde as electrophile allows either an allyl selenide or a b-silyl aldehyde to be obtained, depending upon the reaction conditions used with the hydroxysilane (eq 3).14 With a,b-unsaturated ketones, the lithium reagent (1) adds in the 1,2-sense; the Grignard analog can provide 1,4-addition.15 The cuprate derived from (1) undergoes the expected reactions for this class of compounds, such as 1,4-addition.16

Reaction with Carboxylic Acid Derivatives.

Reaction of (1) with carboxylic acid derivatives provides b-silyl ketones (3) (eq 4). The reaction yield is very dependent upon the presence of a-hydrogens in the substrate; lower yields are obtained when deprotonation can occur at this center.2 The reaction occurs with esters, lactones, acid chlorides, and the parent carboxylic acids.7,17 The resultant b-silyl ketones can be desilylated by simple hydrolysis,2 or used as a substrate in a Peterson alkenation approach to enones.1b The use of a cerium reagent with the acid chloride has been advocated for the preparation of allylsilanes.18

Other Electrophiles.

A mixed higher order cuprate derived from (1) allows for the stereoselective preparation of allylsilanes through an epoxide ring opening (eq 5); use of a lower order cuprate results in low yields and mixtures of products.3

The organolithium reagent (1) also reacts with a wide variety of other electrophiles, including silyl chlorides to provide bis(silyl)methane derivatives,4a,19 and nitriles to provide b-silyl amines after in situ reduction of the intermediate imine derivative.20 a-Silyl epoxides are opened to provide the substituted vinylsilane.21 Reaction of (1) with arenesulfonyl fluorides provides a-silyl sulfones,16c key intermediates for the preparation of vinyl sulfones.5b,c,22 Reaction of the lithium reagent (1) with Aluminum Chloride followed by a vinyl triflate results in formation of an allylsilane (eq 6).23 With Carbon Monoxide as an electrophile with (1), a rapid entry to acylsilanes, or silyl enol ethers by subsequent reaction with Chlorotrimethylsilane, can be realized.24 The alkyllithium (1) is the precursor to a wide variety of organometallic compounds that contain the trimethylsilylmethyl ligand.25

Analogs.

The displacement of a heteroatom to introduce the lithium allows for a wide range of substituted analogs of the reagent (1) to be prepared.1b,5,26 The presence of an aromatic group on the same carbon atom as the silyl moiety allows for direct deprotonation by butyllithium to form the lithium reagent.27 Higher alkyl analogs of (1) are also available by the addition of an alkyllithium to a vinylsilane.1a,10,27,28 All of these higher homologs react with carbonyl compounds and other electrophiles, as expected.1b,d

Related Reagents.

Bis(trimethylsilyl)methane; (Diisopropoxymethylsilyl)methylmagnesium Chloride; Trimethylsilylmethylmagnesium Chloride; (Trimethylstannylmethyl)lithium.


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David J. Ager

The NutraSweet Company, Mount Prospect, IL, USA



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