Ether and Acetal Protecting Groups

Ether and Acetal Protecting Groups. A simple way to protect the OH of an alcohol is as its methyl ether (-OMe). Reaction of an alcohol with a base [often sodium hydride (NaH) in THF or DMF] gives an alkoxide. Subsequent reaction with iodomethane gives the methyl ether via an Sn2 reaction (sec. 2.7.A.i). Formation of dialkyl ethers via reaction of an alkoxide with an alkyl halide is called the Williamson ether 

The MTM group was used to protect several of the alcohol groups in Corey s synthesis of erythronolide A.31 Alcohol 47 contains a sensitive OH group, and it was converted to the MTM derivative (48). This allowed the construction of the tris-MTM lactone (49). Treatment with potassium carbonate (K2CO3) and iodo-methane in aqueous acetone (40°C, 15 h) gave the triol (50) in 80% yield, which was converted to erythronolide A. 

A variation of the OMEM group is the 2-(trimethylsilyl)ethoxymethyl ether (0-CH20CH2CH2-SiMc3, 

O—SEM), developed by Lipshutz. S The trimethylsilyl group is used as a trigger for facile deprotection of 

60 will exist as diastereomers, which may make identification, isolation, and purification difficult if this protecting group is carried through many synthetic steps. This group is stable to base (pH 6-12) but unstable to aqueous acid and to Lewis acids.It is relatively stable to nucleophiles and organometallics. It is also 

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