Reactions at Oxygen Atoms
2.1
107
ic chemistry [1,2,3,4]. In addition to this fact, it is important to point out that in carbohydrate derivatives protecting groups do more than protect; they also confer other effects to the
molecule and can alter the course of a reaction. Important examples of such effects are the use
of 2-O-participating groups in glycosyl donors [5] or the armed/disarmed concept for glycoside coupling [6].
This chapter aims to impart general synthetic strategies for most sugars and oligosaccharide
structures through the use of some basic, well-proven protecting groups, coupled with general
strategies towards regioselectivity. The discussion outlines frequently used protecting groups
in carbohydrate chemistry, briefly surveying conditions for their introduction, stability, and
removal. It should be noted at this stage that the hydroxyl group of the anomeric center, is
unique in having two attached oxygen atoms and therefore it will be treated in a separated
section.
2 Reactions at Non-Anomeric Hydroxyl Groups
2.1 Alkylation Reactions: Ether-Type Protecting Groups
Alkyl and aryl ethers are relatively stable to acids and bases due to the high C–O bond energy
and it is difficult to recover the parent alcohols from them; therefore, most useful ether-type
protections utilize resonance stabilization (by delocalization) of the benzylic-type cation or
radical to facilitate the cleavage.
2.1.1 Methyl Ethers
Conversion to methyl ethers of non-anomeric hydroxyl groups is a long-established procedure
used, in conjunction with ethylation and deutero-methylation, for the analysis of glycosides,
oligosaccharides, and polysaccharides.
Methyl ethers are not normally regarded as protecting groups (though they may be considered
in special cases [7]) because the removal is difficult requiring conditions not compatible with
other functional groups. A recent study has demonstrated a wide range of susceptibilities to
methylation of the hydroxyls in various methyl pyranosides using diazomethane together with
transition-metal chlorides and boric acid [8]. On the other hand, the selective removal of an
⊡ Scheme 1
Selective removal of methoxy protecting groups
2.1
107
ic chemistry [1,2,3,4]. In addition to this fact, it is important to point out that in carbohydrate derivatives protecting groups do more than protect; they also confer other effects to the
molecule and can alter the course of a reaction. Important examples of such effects are the use
of 2-O-participating groups in glycosyl donors [5] or the armed/disarmed concept for glycoside coupling [6].
This chapter aims to impart general synthetic strategies for most sugars and oligosaccharide
structures through the use of some basic, well-proven protecting groups, coupled with general
strategies towards regioselectivity. The discussion outlines frequently used protecting groups
in carbohydrate chemistry, briefly surveying conditions for their introduction, stability, and
removal. It should be noted at this stage that the hydroxyl group of the anomeric center, is
unique in having two attached oxygen atoms and therefore it will be treated in a separated
section.
2 Reactions at Non-Anomeric Hydroxyl Groups
2.1 Alkylation Reactions: Ether-Type Protecting Groups
Alkyl and aryl ethers are relatively stable to acids and bases due to the high C–O bond energy
and it is difficult to recover the parent alcohols from them; therefore, most useful ether-type
protections utilize resonance stabilization (by delocalization) of the benzylic-type cation or
radical to facilitate the cleavage.
2.1.1 Methyl Ethers
Conversion to methyl ethers of non-anomeric hydroxyl groups is a long-established procedure
used, in conjunction with ethylation and deutero-methylation, for the analysis of glycosides,
oligosaccharides, and polysaccharides.
Methyl ethers are not normally regarded as protecting groups (though they may be considered
in special cases [7]) because the removal is difficult requiring conditions not compatible with
other functional groups. A recent study has demonstrated a wide range of susceptibilities to
methylation of the hydroxyls in various methyl pyranosides using diazomethane together with
transition-metal chlorides and boric acid [8]. On the other hand, the selective removal of an
⊡ Scheme 1
Selective removal of methoxy protecting groups