2- ethers protect alcohols

Dahlen, A, Sundgren, A, Lahmann, M, Oscarson, S, Hilmersson, G, Sml2/water/amine mediates cleavage of allyl ether protected alcohols — application in carbohydrate synthesis and mechanistic considerations, Org. Lett, 5, 4058-4088, 2003. 

The SmI2-II20 amine system has also been used for the selective cleavage of allyl ether-protected alcohols (Scheme 8.14). This method shown to be useful in the deprotection of alcohols and carbohydrates.16... 

Silyl ether protected alcohols (eq 5) have been converted directly into the corresponding bromides with PhaP and CBr4. The reaction works best if 1.5 equiv of acetone are added. Tetrahy-dropyranyl ether protected alcohols have also been directly transformed into the bromides using this reagent combination. The reaction has been reported to proceed with inversion of configuration (eq 6). If unsaturation is appropriately placed within a tetrahydropyranyl (eq 7) or a methoxymethyl (eq 8) protected alcohol, cyclization occurs to afford tetrahydropyrans. The conversion of an alcohol to the bromide without complications with a methoxymethyl protected alcohol in the molecule is possible (eq 9).i ... 

The most stable protected alcohol derivatives are the methyl ethers. These are often employed in carbohydrate chemistry and can be made with dimethyl sulfate in the presence of aqueous sodium or barium hydroxides in DMF or DMSO. Simple ethers may be cleaved by treatment with BCI3 or BBr, but generally methyl ethers are too stable to be used for routine protection of alcohols. They are more useful as volatile derivatives in gas-chromatographic and mass-spectrometric analyses. So the most labile (trimethylsilyl ether) and the most stable (methyl ether) alcohol derivatives are useful in analysis, but in synthesis they can be used only in exceptional cases. In synthesis, easily accessible intermediates of medium stability are most helpful. 

The /-butyldimethylsilyl group introduced by TBDMIM has a number of advantages in protecting alcohols (6). The sdylated alcohol hydroly2es more slowly than an alcohol sdylated with TMS by a factor of 10 . The sdyl ether is also stable to powerful oxidi2ing and reducing agents, but it can easily be removed by aqueous acetic acid or tetrabutylammonium fluoride in tetrahydrofuran. 

Ethers are among the most used protective groups in organic synthesis. They vary from the simplest, most robust, methyl ether to the more elaborate, substituted, trityl ethers developed for use in nucleotide synthesis. They are formed and removed under a wide variety of conditions. Some of the ethers that have been used to protect alcohols are included in Reactivity Chart 1. ... 

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

The ability to convert a protective group to another functional group directly without first performing a deprotection is a potentially valuable transformation. Silyl-protected alcohols have been converted directly to aldehydes, ketones, bro-mides, acetates, and ethers without first liberating the alcohol in a prior deprotection step. 

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