Reactions at Oxygen Atoms
2.1
129
⊡ Figure 4
Principal members of the alkoxymethyl ether family
Usually, the formation of the alkoxymethyl ethers is effected by reaction of the corresponding chloride with either the sodium or lithium salt of the alcohol to be protected. The resulting ethers are stable to a wide variety of conditions including many organometallic reagents,
reducing conditions, oxidizing agents, and mild acids. Indeed a number of the alkoxymethyl
ethers are orthogonal to each other and can be used strategically in multistep syntheses. For
example, SEM, BOM, and PMBM ethers are cleaved using a fluoride source, hydrogenolysis
and oxidation, respectively. The alkoxymethyl ethers also vary in their degree of lability to
Brønsted acids with MOM ether being the most robust.
The SEM group can be removed under milder reaction conditions than the MEM or MOM
analogs. As shown in > Scheme 28, the compatibility of this group with the conditions required
for other selective functional group transformation, together with its stability under glycosylation conditions, allowed the preparation of rhamnopyranosyl synthons for the elaboration of
higher order oligosaccharides ( > Scheme 28) [193].
The 1-[2-(trimethylsilyl)ethoxy]ethyl (SEE) group closely resembles the SEM group and can
be introduced to alcohols with 2-(trimethylsilyl)ethyl vinyl ether in the presence of a catalytic
amount of PPTS under neutral or slightly acidic conditions [194]. The SEE group can be
removed with TBAF in THF (24 h, rt. to 45 °C).
2.3 Acylation Reactions: Ester-Type Protecting Groups
Acylation of hydroxyl groups of carbohydrates is one of the most commonly used functional group protection techniques in the synthesis of oligosaccharides. Acyl groups are readily
introduced with many acylating agents of different reactivity. They are easily removed under
basic (aqueous or non-aqueous) conditions, but are fairly stable under acidic conditions. The
main drawback of esters as protecting groups is that they have a tendency to migrate (especially acetates), both under acidic and basic conditions. This is a concern in partially protected
derivatives, and results in a mixture with the most stable compound preponderant. Thus, in
cis-hydroxyls, there is normally a preferred migration from the axial position to the equatorial
one and in 4,6-diols the migration goes from O-4 to O-6 preferentially [195].
2.1
129
⊡ Figure 4
Principal members of the alkoxymethyl ether family
Usually, the formation of the alkoxymethyl ethers is effected by reaction of the corresponding chloride with either the sodium or lithium salt of the alcohol to be protected. The resulting ethers are stable to a wide variety of conditions including many organometallic reagents,
reducing conditions, oxidizing agents, and mild acids. Indeed a number of the alkoxymethyl
ethers are orthogonal to each other and can be used strategically in multistep syntheses. For
example, SEM, BOM, and PMBM ethers are cleaved using a fluoride source, hydrogenolysis
and oxidation, respectively. The alkoxymethyl ethers also vary in their degree of lability to
Brønsted acids with MOM ether being the most robust.
The SEM group can be removed under milder reaction conditions than the MEM or MOM
analogs. As shown in > Scheme 28, the compatibility of this group with the conditions required
for other selective functional group transformation, together with its stability under glycosylation conditions, allowed the preparation of rhamnopyranosyl synthons for the elaboration of
higher order oligosaccharides ( > Scheme 28) [193].
The 1-[2-(trimethylsilyl)ethoxy]ethyl (SEE) group closely resembles the SEM group and can
be introduced to alcohols with 2-(trimethylsilyl)ethyl vinyl ether in the presence of a catalytic
amount of PPTS under neutral or slightly acidic conditions [194]. The SEE group can be
removed with TBAF in THF (24 h, rt. to 45 °C).
2.3 Acylation Reactions: Ester-Type Protecting Groups
Acylation of hydroxyl groups of carbohydrates is one of the most commonly used functional group protection techniques in the synthesis of oligosaccharides. Acyl groups are readily
introduced with many acylating agents of different reactivity. They are easily removed under
basic (aqueous or non-aqueous) conditions, but are fairly stable under acidic conditions. The
main drawback of esters as protecting groups is that they have a tendency to migrate (especially acetates), both under acidic and basic conditions. This is a concern in partially protected
derivatives, and results in a mixture with the most stable compound preponderant. Thus, in
cis-hydroxyls, there is normally a preferred migration from the axial position to the equatorial
one and in 4,6-diols the migration goes from O-4 to O-6 preferentially [195].