Ether formation methanolysis

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°. ... 

Not surprisingly, an attempt at direct Mitsunobu inversion of (3-hydroxyketone 14 led only to elimination, yielding the corresponding a,(3-unsaturated ketone. To circumvent this problem, 14 was converted to homoallylic alcohol 15 by Petasis methylenation via the corresponding TES ether. Attempts to methylenate (3-hydroxyketone 14 directly under Petasis conditions led to substantial decomposition via elimination and retro-aldol pathways. Alcohol 15 underwent smooth Mitsunobu inversion to give, following methanolysis and TES ether formation, the desired 1,4-anti compound 16 (Scheme 3). This was then converted in three straightforward steps to aldehyde 17, ready for the proposed aldol union with ketone 10. 

Fig (12) Transformation of keto ester (94) to (96) is described. Michael addition leads the formation of the adduct (97) which is subjected to cyclization, aromatization and hydrogenolysis to obtain the phenol (99). This on diazotization, methylation and reduction afforded the amino ether (100). Further diazotization, methanolysis and saponification produce ethyl (+)-camosic acid dimethylether (102). 

A different approach to the synthesis of sulfate esters was discussed by Buncel and co-workers (97 ). The sulfate monoester was obtained after neutral or alkaline methanolysis of methyl 4-nltro-phenyl sulfate. The methoxide Ion attacks only at the alkyl carbon with the formation of dimethyl ether and 4-nltrophenyl sulfate Ion as the leaving group. Other substituted methyl phenyl sulfates have been converted to phenyl sulfates In the same manner (98). Correspondingly l,2 5,6-dl-0-lsopropylldlne-a-D-glucofuranose was reacted with phenyl chlorosulfate to give the carbohydrate... 

The configuration of a keto-ether (301 R = OMe) obtained in 28% yield on methanolysis of the diazoketone (301 R = Nj) has been shown to have the i -glycero-ii-galacto configuration, rather than the d- or. -glycero- j-altro configuration previously suggested by c.d. (see Vol. 8, p. 135), by formation of the AT-acetyl-lincosamine derivative (302) and its C-6 epimer. ... 

Also itermolecular photochemical [2+2] cycloaddition based on 2-trifluoromethylquinazoline 1286 was studied. In a similar conditions the reaction with ethylene gives compound 1287 in 17 % yield as a sole product probably due to low solubility of ethylene in methanol. Ene-type product 1288 was isolated in 65 % yield when isobutylene was used in the reaction, showing that biradical intermediate is involved in the transformation. In a case of ethyl vinyl ether acetal 1292 was formed as product of methanolysis of intermediate azetidine 1289. Similarly was used intermediate azetidine 1290 was not isolated when dichloroethylene and its formation was proved by isolation of methanolysis product 1293 in 89 % yield. It should be noted, that treatment of product 1288 with base leads to elimination of CFs-group as in a case of 1284 (Scheme 298) [797]... 

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