Ethers, methyl iodotrimethylsilane

The use of iodotrimethylsilane for this purpose provides an effective alternative to known methods. Thus the reaction of primary and secondary methyl ethers with iodotrimethylsilane in chloroform or acetonitrile at 25—60° for 2—64 hours affords the corresponding trimethylsilyl ethers in high yield. The alcohols may be liberated from the trimethylsilyl ethers by methanolysis. The mechanism of the ether cleavage is presumed to involve initial formation of a trimethylsilyl oxonium ion which is converted to the silyl ether by nucleophilic attack of iodide at the methyl group. tert-Butyl, trityl, and benzyl ethers of primary and secondary alcohols are rapidly converted to trimethylsilyl ethers by the action of iodotrimethylsilane, probably via heterolysis of silyl oxonium ion intermediates. The cleavage of aryl methyl ethers to aryl trimethylsilyl ethers may also be effected more slowly by reaction with iodotrimethylsilane at 25—50° in chloroform or sulfolane for 12-125 hours, with iodotrimethylsilane at 100—110° in the absence of solvent, " and with iodotrimethylsilane generated in situ from iodine and trimcthylphenylsilane at 100°. ... 

Reactions.—A new study of the reaction of various ethers with iodotrimethylsilane has appeared. Dialkyl ethers are found to be cleaved (Scheme 41), methyl ethers showing predominant demethylation and aryl alkyl ethers leading to exclusive... 

Boron tribromide is reported to be more effective than iodotrimethylsilane for cleaving aryl methyl ethers. ... 

Likewise, synthetic 2//-azepines isomerize to 3//-azepines in refluxing chloroform (2-3 h) or in tert-butyl methyl ether at room temperature.291 The isomers can be readily separated by chromatography on silica gel, as the more basic 2//-azepines30 have lower Rf values. In contrast, 7-butyl-2//-azepin-2-acetic acid (11), obtained by heating the tert-butyl ester 10 with iodotrimethylsilane, is stabilized by intramolecular hydrogen bonding and shows no tendency to rearrange to the 3//-isomer.291... 

When an insufficient amount of iodotrimethylsilane was used by the submitters, cyclohexyl methyl ether remained at the end of the reaction and was eluted from the silica gel column before cyclohexanol. When present in the crude product, cyclohexyl iodide was also eluted from the column before cyclohexanol. 

Alkyl esters are efficiently dealkylated to trimethylsilyl esters with high concentrations of iodotrimethylsilane either in chloroform or sulfolane solutions at 25-80° or without solvent at 100-110°.Hydrolysis of the trimethylsilyl esters serves to release the carboxylic acid. Amines may be recovered from O-methyl, O-ethyl, and O-benzyl carbamates after reaction with iodotrimethylsilane in chloroform or sulfolane at 50—60° and subsequent methanolysis. The conversion of dimethyl, diethyl, and ethylene acetals and ketals to the parent aldehydes and ketones under aprotic conditions has been accomplished with this reagent. The reactions of alcohols (or the corresponding trimethylsilyl ethers) and aldehydes with iodotrimethylsilane give alkyl iodides and a-iodosilyl ethers,respectively. lodomethyl methyl ether is obtained from cleavage of dimethoxymethane with iodotrimethylsilane. 

Cleavage of methyl and benzyl ethers.2 These ethers are cleaved by the combination of this silane and zinc iodide. The rate of dealkylation is enhanced by the presence of ( -C4H9)4NI. Trimethyl(methylthio)silane serves the same purpose. CH2C12 and C1CH2CH2C1 are satisfactory solvents. The cleavage probably does not involve in situ formation of iodotrimethylsilane. 

Methyl ethers are stable to acidic and basic conditions, and oxidising or reducing reagents. Deprotection to regenerate the alcohol is difficult (see Section 9.6.10, p. 1254) a convenient mild procedure uses iodotrimethylsilane in chloroform solution at room temperature.768 The alkyl methyl ether under these conditions gives the alkyl silyl ether and methyl iodide the former on treatment with methanol gives the deprotected alcohol. 

Deprotection of aryl methyl ethers may be effected under strongly acidic conditions (e.g. hydriodic acid, Section 9.6.11, p. 1253), but the milder methods employing either iodotrimethylsilane in chloroform solution at 20-50 °C for several hours,40 or boron tribromide at room temperature may be preferable.41... 

Me3SiI, CHC13, 25-50°, 12-140 h.8 Iodotrimethylsilane in quinoline (180°, 70 min) selectively cleaves an aryl methyl group, in 72% yield, in the presence of a methylenedioxy group.9 Me3SiI cleaves esters more slowly than ethers and cleaves alkyl aryl ethers (48 h, 25°) more slowly than alkyl alkyl ethers (1.3-48 h, 25°), but benzyl, trityl, and /-butyl ethers are cleaved quite rapidly (0.1 h, 25°).7... 

Cleavage of MEM ethers.1 2-Methoxy ethoxy methyl (MEM) ethers are cleaved by NaI/ClSi(CH3)3 in CH3CN at —20 or 25° in moderate to high yield. Iodotrimethylsilane (commercial) is less effective. Fairly selective cleavage of MEM ethers is possible in the presence of lactones, methyl or benzyl ethers, and methyl esters. 

Deoxygenation of aieohols and ethers. Treatment of alcohols and methyl or trimethylsilyl ethers in acetonitrile with this iodotrimethylsilane equivalent and then zinc (previously activated with aqueous hydrochloric acid) and a little acetic acid results in deoxygenation to alkanes, usually in 60-90% yield. Presumably an alkyl iodide is an intermediate. 

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