Ethers, methoxymethyl alcohol protection

Protection of tertiary alcohols. Methylthidiiiethyl (MTM) ethers have the advantage that they can be prepared from tertiary alcolols (7,135), but the disadvantage that they are prone to oxidation. They can be convcrtcil into 2-mcthoxycthoxymethyl (MEM) ethers, methoxymethyl (MOM) ethers, or ethoxy methyl (EOM) ethers by reaction with... 

In order to achieve controlled polymerization from die bdk ligand, an ethanol moiety is introduced to the phenol site to provide a primary alcohol site, and a less sterically crowded enviromnent for initiation (Figure 4). The alcohol requires protection in order to prevent deprotonation under die basic reaction conditions required for the ester and ketone condensation. A number of protecting groups were screened for this purpose, and one promising strategy involves methoxymethyl (MOM) protection. The formation of the MOM ether proceeds in nearly quantitative yield. After the condensation, the MOM group can be removed with aqueous HCl in THF. 

The benzyl ether is prepared in a similar manner to the methoxymethyl ether, that is, by reaction of the conjugate base of the alcohol with benzyl bromide in an SN2 reaction. An example of a sequence that employs a benzyl ether protecting group is illustrated in the following sequence ... 

A mild procedure for the appendage of MOM groups to acid-sensitive substrates is illustrated by the protection of the allylic alcohol in Avermectin derivative 259.1 using [(methoxymethyl)thio]-2-pyridine (259 2) sitver(I) Inflate and sodium acetate in THF at room temperature [Scheme 4.259],479 Primary secondary and tertiary alcohols and phenols are methoxymethylated in good yield though phenols are slower to react. Reagent 259.2 (bp 66 °C/0.088 kPa) is easily prepared in 75% yield by the reaction of pyridine-2-thiol with dimethoxy-methane activated by trifluoroborane etherate. 

Selective formation of the methyl enol ether and reduction of the C(11) keto function followed by protection of the resultant alcohol as methoxymethyl ether provided (275). 

Cleavage of MOM ethers. This combination of reagents enables smooth removal of the methoxymethyl group from protected 1,3-diols and 1,3-amino alcohols in dichloromethane. Complications arise if acetic acid is omitted. For example, 1,3-oxazines are formed in the case of protected 3-aminopropyl methoxymethyl ethers. 

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