Trimethylsilylmethylmagnesium Chloride1

[13170-43-9]  · C4H11ClMgSi  · Trimethylsilylmethylmagnesium Chloride  · (MW 147.00)

(methylenation of carbonyl compounds;1b,2 provides a variety of methods to prepare allylsilanes1k)

Solubility: sol ethereal solvents; reacts with protic solvents.

Preparative Method: from (Chloromethyl)trimethylsilane and Magnesium in an ethereal solvent.3,4

Handling, Storage, and Precautions: this Grignard reagent reacts with protic solvents.

Peterson Alkenation.

Trimethylsilylmethylmagnesium chloride (1) reacts with carbonyl compounds to give b-hydroxysilanes (2).2,4,5 These silanes can then be eliminated to provide an alkene under acidic or basic conditions, such as with Sodium Hydride or Potassium Hydride (eq 1).1a,1b,5,6 The elimination can also be accomplished by Acetyl Chloride or Thionyl Chloride.7 For the introduction of exo-methylene groups, reagent (1) has been found to be superior to a Wittig approach;8 the silicon reagent reacts rapidly and the byproduct is simple to remove.1b

This methodology has found application in the carbohydrate field for homologation of a saccharide,9 as other functional groups can be tolerated.1b,10 The resultant alkene can be functionalized in a wide variety of ways.11 The use of Paraformaldehyde as electrophile provides a simple method to 2-(Trimethylsilyl)ethanol.12

Many of the uses of the Grignard reagent (1) are complementary to those of Trimethylsilylmethyllithium, although the cerium reagent derived from the lithium analog provides higher yields with enolizable aldehydes and ketones.13

With a,b-unsaturated carbonyl compounds the Grignard reagent reacts in a 1,2-manner,14 although 1,4-addition can be observed in certain cases.15 The resultant b-hydroxysilane from a 1,2-addition can be isomerized to the b-ketosilane with a rhodium catalyst.16 In the presence of copper(I), the Grignard reagent (1) reacts in a 1,4-manner with a,b-unsaturated carbonyl compounds.15,17

The use of substituted carbonyl compounds allows for the formation of functionalized alkenes; for example, a,b-epoxy ketones afford the monoepoxide of a diene.18 The successive treatment of a-chlorocarbonyl compounds with (1) and Lithium powder provides a regioselective entry to allylsilanes (eq 2).19

Reagent (1) does also react with imines that, in turn, can be generated in situ.20

Reaction with Carboxylic Acid Derivatives.

In addition to carbonyl compounds, reagent (1) also reacts with carboxylic acid derivatives.4 Thus lactones provide hydroxy allylsilanes (3) (eq 3).21

Reaction of excess (1) with esters provides the tertiary alcohol in an analogous manner,1d and subsequent elimination provides the allylsilane.22 The addition of the second equivalent of (1), however, is dependent on the steric requirements of the intermediate b-silyl ketone.23 The addition of Chlorotrimethylsilane to the reaction mixture has been advocated as higher yields of the resultant allylsilane are obtained.24 The use of Cerium(III) Chloride with Grignard reagent (1) promotes nucleophilic attack on esters, and the allylsilanes can be obtained in high yield (eq 4).25 The yields seem to be higher than for the analogous reaction between an acid chloride and the cerium reagent prepared from trimethylsilylmethyllithium.26 1,2-Addition is observed with a,b-unsaturated esters.25 Other functional groups, such as acetals, thioacetals, halogens, hydroxy, acetates, and sulfides, can be incorporated at the a-position of the ester group without detrimental effects.27

Reaction with diketene in the presence of a nickel catalyst gives 3-(trimethylsilylmethyl)but-3-enoic acid (4) (eq 5).28

The Grignard reagent (1) does react with acid chlorides to provide ketones after hydrolytic workup.2 The use of a copper(I) catalyst allows isolation of b-silyl ketones (eq 6).29

b-Silyl ketones are hydrolytically unstable and can be converted to the desilylated ketone by simple acid or base treatment,30 or used in a Peterson alkenation reaction to provide enones.1b,29a They are also precursors to silyl enol ethers by rearrangement.29c,31 Reaction of the b-silyl ketone with a vinyl Grignard reagent provides a rapid entry to 2-substituted 1,3-dienes by a Peterson protocol.32

Reaction of (1) with Carbon Dioxide provides Trimethylsilylacetic Acid,33 while treatment of (1) with Ethyl Chloroformate gives Ethyl Trimethylsilylacetate.34 The use of ethyl oxalyl chloride as substrate for (1) provides a simple preparation of ethyl 2-(trimethylsilylmethyl)propenoate.35 Condensation of (1) with benzonitrile resulted in isolation of acetophenone (64%) and desoxybenzoin (45%).4

Reaction with Alkyl Halides.

The Grignard reagent (1) can be alkylated by allyl halides to afford the homoallylsilane.4,36 The use of a nickel(II) catalyst facilitates coupling of the Grignard reagent (1) to vinyl halides37 and aryl halides, triflates and O-carbamates38 and provides a useful method for the preparation of allyl- and benzylsilanes (eq 7). Palladium catalysis is also effective to couple (1) with vinyl halides.37b,39

Reaction with Sulfur Compounds.

In a similar coupling reaction to those of alkyl halides, (1) reacts in the presence of a nickel catalyst with allylic dithioacetals to yield 1-(trimethylsilyl)butadienes (eq 8).40

Dithioacetals derived from alkyl aryl ketones react with the Grignard reagent (1) in the presence of a nickel catalyst.41,42 The use of an orthothioester as substrate in place of a thioacetal provides 1,3-bis(trimethylsilyl)propenes as a mixture of the (E)- and (Z)-isomers.43 With a-oxoketene dithioacetals (5), the Grignard reagent (1) reacts, in the presence of Copper(I) Iodide, to provide 1-trimethylsilyloxy-3-thiadienes (eq 9).44

Reaction with Other Electrophiles.

Reaction occurs between (1) and epoxides to yield g-hydroxysilanes.45 Michael addition is observed with nitroalkenes; the silyl group can then promote a Nef reaction to afford b-silyl ketones (eq 10).46

With aromatic nitro compounds, nucleophilic addition of (1) occurs on the aromatic nucleus (eq 11).47

A nickel catalyst allows reaction between (1) and an enol phosphate,48 silyl enol ether,49 or substituted dihydrofurans50 and dihydropyrans51 to afford allylsilanes. Additional functionality can be tolerated in the substrate.52

Coupling of (1) with propargylic tosylates, mesylates, or acetates in the presence of copper(I) leads to a-trimethylsilylallenes,53 while the use of a propargyl alcohol substrate leads to the substituted allylsilane (eq 12).54

With alkynes, copper-catalyzed addition of the Grignard reagent (1) provides the allylsilane.55 The intermediate vinylcopper reagent can also be trapped with electrophiles.56

The reagent (1) also reacts with wide variety of electrophiles, including carbon dioxide,33 cyanogen,57 silyl chlorides,3,58 metal halides,59 and Phosphorus(III) Chloride.59a With methyl phenyl sulfinate, reaction of (1) leads to the formation of (phenylthio)(trimethylsiloxy)methane, a protected form of formaldehyde, by a sila-Pummerer rearrangement.60

The Grignard reagent (1) is the precursor of numerous organometallic compounds that contain the trimethylsilylmethyl ligand.61

Related Reagents.

(Diisopropoxymethylsilyl)methylmagnesium Chloride; Trimethylsilylmethylpotassium; (Trimethylstannylmethyl)lithium.


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David J. Ager

The NutraSweet Company, Mount Prospect, IL, USA



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