Page 288 - Advanced Organic Chemistry Part B - Reactions & Synthesis

260 is introduced, and this acetal offers the further advantage of being hydrolyzed under
somewhat milder conditions than those required for THP ethers. 155
CHAPTER 3
Functional Group H +
Interconversion ROH + CH 2 C OCH 3 ROC(CH ) OCH 3
3 2
by Substitution,
Including Protection and CH 3
Deprotection
Ethyl vinyl ether is also useful for hydroxy group protection. The resulting derivative
(1-ethoxyethyl ether) is abbreviated as the EE group. 156 As with the THP group, the
EE group introduces an additional stereogenic center.
The methoxymethyl (MOM) and -methoxyethoxymethyl (MEM) groups are used
to protect alcohols and phenols as formaldehyde acetals. These groups are normally
introduced by reaction of an alkali metal salt of the alcohol with methoxymethyl
chloride or -methoxyethoxymethyl chloride. 157

CH OCH Cl ROCH OCH 3
2
2
3
–
RO M +
ROCH OCH CH OCH
CH OCH CH OCH Cl 2 2 2 3
3
2
2
2
The MOM and MEM groups can be cleaved by pyridinium tosylate in moist organic
solvents. 158 An attractive feature of the MEM group is the ease with which it can be
removed under nonaqueous conditions. Reagents such as zinc bromide, magnesium
bromide, titanium tetrachloride, dimethylboron bromide, or trimethylsilyl iodide permit
its removal. 159 The MEM group is cleaved in preference to the MOM or THP groups
under these conditions. Conversely, the MEM group is more stable to acidic aqueous
hydrolysis than the THP group. These relative reactivity relationships allow the THP
and MEM groups to be used in a complementary fashion when two hydroxy groups
must be deprotected at different points in a synthetic sequence.
CH 2 CH CH 2 CH
CH CO H, H O,
3
2
2
THF
OMEM 35°C, 40h OMEM
THPO HO Ref. 160
The methylthiomethyl (MTM) group is a related alcohol-protecting group. There
are several methods for introducing the MTM group. Alkylation of an alcoholate by

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157
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160
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